# data[].attributes.body
A stressful situation (environmental or psychological) can trigger stress hormones that produce physiological changes.

It can make the heart pound and breathing quicken, muscles tense and cause sweat.

The fight-or-flight response is as a survival mechanism, enabling mammals to react quickly to life-threatening situations.

Continous stress response takes a toll on the body. Research suggests that chronic stress contributes to high blood pressure, promotes the formation of artery-clogging deposits, and causes brain changes that may contribute to anxiety, depression, and addiction.

The autonomic nervous system has two components:

The sympathetic nervous system functions like a gas pedal in a car. It triggers the fight-or-flight response, providing the body with a burst of energy so that it can respond to perceived dangers.

The parasympathetic nervous system acts like a brake. It promotes the "rest and digest" response that calms the body down after the danger has passed.

After the amygdala sends a distress signal, the hypothalamus activates the sympathetic nervous system and these glands respond by pumping adrenaline into the bloodstream.

Adrenaline = heart beats faster, pushing blood to the muscles, heart, and other vital organs, pulse rate and blood pressure go up, rapid breathing.

When the adrenaline rush subsides, the hypothalamus activates the second component of the stress response system - the HPA axis (consists of the hypothalamus, the pituitary gland, and the adrenal glands)

The HPA axis relies on hormonal signals to keep the sympathetic nervous system pressed down. If the brain continues to perceive something as dangerous, the hypothalamus releases CRH, which travels to the pituitary gland, triggering the release of ACTH - This hormone travels to the adrenal glands, prompting them to release cortisol. The body thus stays revved up and on high alert.

When the threat passes, cortisol levels fall.

Persistent adrenaline surges can damage blood vessels and arteries, increasing blood pressure and raising risk of heart attacks or strokes.

Elevated cortisol levels create physiological changes that help to replenish the body's energy stores that are depleted during the stress response.

The also contribute to the buildup of fat tissue and to weight gain as cortisol increases appetite.

# data[].attributes.attachment_link.readable_text
A stressful situation - whether something environmental, such as a looming work deadline, or psychological, such as persistent worry about losing a job - can trigger a cascade of stress hormones that produce well-orchestrated physiological changes. A stressful incident can make the heart pound and breathing quicken. Muscles tense and beads of sweat appear.

This combination of reactions to stress is also known as the "fight-or-flight" response because it evolved as a survival mechanism, enabling people and other mammals to react quickly to life-threatening situations. The carefully orchestrated yet near-instantaneous sequence of hormonal changes and physiological responses helps someone to fight the threat off or flee to safety. Unfortunately, the body can also overreact to stressors that are not life-threatening, such as traffic jams, work pressure, and family difficulties.

Over the years, researchers have learned not only how and why these reactions occur, but have also gained insight into the long-term effects chronic stress has on physical and psychological health. Over time, repeated activation of the stress response takes a toll on the body. Research suggests that chronic stress contributes to high blood pressure, promotes the formation of artery-clogging deposits, and causes brain changes that may contribute to anxiety, depression, and addiction.. More preliminary research suggests that chronic stress may also contribute to obesity, both through direct mechanisms (causing people to eat more) or indirectly (decreasing sleep and exercise).

Sounding the alarm

The stress response begins in the brain (see illustration). When someone confronts an oncoming car or other danger, the eyes or ears (or both) send the information to the amygdala, an area of the brain that contributes to emotional processing. The amygdala interprets the images and sounds. When it perceives danger, it instantly sends a distress signal to the hypothalamus.

Command center

When someone experiences a stressful event, the amygdala, an area of the brain that contributes to emotional processing, sends a distress signal to the hypothalamus. This area of the brain functions like a command center, communicating with the rest of the body through the nervous system so that the person has the energy to fight or flee.

The hypothalamus is a bit like a command center. This area of the brain communicates with the rest of the body through the autonomic nervous system, which controls such involuntary body functions as breathing, blood pressure, heartbeat, and the dilation or constriction of key blood vessels and small airways in the lungs called bronchioles. The autonomic nervous system has two components, the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system functions like a gas pedal in a car. It triggers the fight-or-flight response, providing the body with a burst of energy so that it can respond to perceived dangers. The parasympathetic nervous system acts like a brake. It promotes the "rest and digest" response that calms the body down after the danger has passed.

After the amygdala sends a distress signal, the hypothalamus activates the sympathetic nervous system by sending signals through the autonomic nerves to the adrenal glands. These glands respond by pumping the hormone epinephrine (also known as adrenaline) into the bloodstream. As epinephrine circulates through the body, it brings on a number of physiological changes. The heart beats faster than normal, pushing blood to the muscles, heart, and other vital organs. Pulse rate and blood pressure go up. The person undergoing these changes also starts to breathe more rapidly. Small airways in the lungs open wide. This way, the lungs can take in as much oxygen as possible with each breath. Extra oxygen is sent to the brain, increasing alertness. Sight, hearing, and other senses become sharper. Meanwhile, epinephrine triggers the release of blood sugar (glucose) and fats from temporary storage sites in the body. These nutrients flood into the bloodstream, supplying energy to all parts of the body.

All of these changes happen so quickly that people aren't aware of them. In fact, the wiring is so efficient that the amygdala and hypothalamus start this cascade even before the brain's visual centers have had a chance to fully process what is happening. That's why people are able to jump out of the path of an oncoming car even before they think about what they are doing.

As the initial surge of epinephrine subsides, the hypothalamus activates the second component of the stress response system - known as the HPA axis. This network consists of the hypothalamus, the pituitary gland, and the adrenal glands.

The HPA axis relies on a series of hormonal signals to keep the sympathetic nervous system - the "gas pedal" - pressed down. If the brain continues to perceive something as dangerous, the hypothalamus releases corticotropin-releasing hormone (CRH), which travels to the pituitary gland, triggering the release of adrenocorticotropic hormone (ACTH). This hormone travels to the adrenal glands, prompting them to release cortisol. The body thus stays revved up and on high alert. When the threat passes, cortisol levels fall. The parasympathetic nervous system - the "brake" - then dampens the stress response.

Techniques to counter chronic stress

Many people are unable to find a way to put the brakes on stress. Chronic low-level stress keeps the HPA axis activated, much like a motor that is idling too high for too long. After a while, this has an effect on the body that contributes to the health problems associated with chronic stress.

Persistent epinephrine surges can damage blood vessels and arteries, increasing blood pressure and raising risk of heart attacks or strokes. Elevated cortisol levels create physiological changes that help to replenish the body's energy stores that are depleted during the stress response. But they inadvertently contribute to the buildup of fat tissue and to weight gain. For example, cortisol increases appetite, so that people will want to eat more to obtain extra energy. It also increases storage of unused nutrients as fat.

Fortunately, people can learn techniques to counter the stress response.

Relaxation response. Dr. Herbert Benson, director emeritus of the Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital, has devoted much of his career to learning how people can counter the stress response by using a combination of approaches that elicit the relaxation response. These include deep abdominal breathing, focus on a soothing word (such as peace or calm), visualization of tranquil scenes, repetitive prayer, yoga, and tai chi.

Most of the research using objective measures to evaluate how effective the relaxation response is at countering chronic stress have been conducted in people with hypertension and other forms of heart disease. Those results suggest the technique may be worth trying - although for most people it is not a cure-all. For example, researchers at Massachusetts General Hospital conducted a double-blind, randomized controlled trial of 122 patients with hypertension, ages 55 and older, in which half were assigned to relaxation response training and the other half to a control group that received information about blood pressure control. After eight weeks, 34 of the people who practiced the relaxation response - a little more than half - had achieved a systolic blood pressure reduction of more than 5 mm Hg, and were therefore eligible for the next phase of the study, in which they could reduce levels of blood pressure medication they were taking. During that second phase, 50% were able to eliminate at least one blood pressure medication - significantly more than in the control group, where only 19% eliminated their medication.

Physical activity. People can use exercise to stifle the buildup of stress in several ways. Exercise, such as taking a brisk walk shortly after feeling stressed, not only deepens breathing but also helps relieve muscle tension. Movement therapies such as yoga, tai chi, and qi gong combine fluid movements with deep breathing and mental focus, all of which can induce calm.

Social support. Confidants, friends, acquaintances, co-workers, relatives, spouses, and companions all provide a life-enhancing social net - and may increase longevity. It's not clear why, but the buffering theory holds that people who enjoy close relationships with family and friends receive emotional support that indirectly helps to sustain them at times of chronic stress and crisis.

# data[].attributes.attachment_link.title
Understanding the stress response - Harvard Health

# data[].attributes.attachment_link.description
Research suggests that chronic stress is linked to high blood pressure, clogged arteries, anxiety, depression, addictive behaviors, and obesity....

# data[].attributes.body
The alarm stage - the central nervous system is awakened, triggering your body’s defenses. This stage results in a fight-or-flight response.

The resistance stage - your body begins to repair itself and normalize heart rate, blood pressure, etc. Your body enters this recovery phase but remains on high alert for a while.

The exhaustion stage - when the first two stages continue over time, it causes an imbalance within your body. This is when certain diseases, such as diabetes or heart disease, may begin.

Affects on physical wellbeing:

Our brain releases adrenaline that triggers a fight-or-flight response, producing adrenaline and secreting cortisol.

Cortisol is a steroid, which can weaken your immune system, increase bone loss, and decrease energy levels.

Adrenaline increases heart rate, breathing and blood pressure. It also causes fat tissue to break down and increases lactic acid in your muscles. With stimulation and increased adrenaline, your liver releases sugar into the bloodstream for energy.

The stimulation of your central nervous and sympathetic nervous system causes salt retention, the elevation of sugar in your bloodstream, increased risk of blood clots, and can even lead to damage to your heart and kidneys.

# data[].attributes.attachment_link.readable_text
Stress is something that we are all aware of daily. Stress can cause bodily or mental tension. But did you know that stress can be both positive and negative? It is your perception of this stress that matters most.

General adaptation syndrome is how your body responds to stress. There are three stages to stress: the alarm stage, the resistance stage and the exhaustion stage.

1. The alarm stage is when the central nervous system is awakened, causing your body's defenses to assemble. This SOS stage results in a fight-or-flight response.

2. The resistance stage is when your body begins to repair itself and normalize heart rate, blood pressure, etc. After the initial shock of a stressful event, your body enters this recovery phase but remains on high alert for a while.

3. The exhaustion stage is when activation in the first two stages continues over time, causing a breakdown in the balance within your body. This is when certain diseases, such as diabetes or heart disease, may begin.

How Does Stress Impact Your Physical Health?

When you experience stress, several things occur impacting your cardiovascular, muscular and nervous systems:

1. Your brain releases a hormone that triggers your body's fight-or-flight response, producing adrenaline and secreting cortisol.

2. Cortisol is a steroid, which can weaken your immune system and the wound-healing process, increase bone loss, and decrease energy levels.

3. Adrenaline increases your heart rate, breathing and blood pressure. It also causes fat tissue to break down and increases lactic acid in your muscles. With stimulation and increased adrenaline, your liver releases sugar into the bloodstream for energy.

4. The stimulation of your central nervous system and sympathetic nervous system causes salt retention, the elevation of sugar in your bloodstream, increased risk of blood clots, and can even lead to damage to your heart and kidneys.

Marathon Health Behavioral Health Counselor Damir Alisa says people might not even realize when stress is impacting their nervous system. "If you're sitting down and suddenly start tapping your foot rapidly but have no idea that you're doing it, that's a sign that your nervous system is being constricted," Alisa explains.

With all this stress on the body, your heart has to work a lot harder, which can cause it to become less effective and less efficient. Less blood will travel to your vital organs, which can limit their ability to function properly. Prolonged stress can also increase your risk of disease and contribute to pre-existing conditions while also weakening your immune system.

Additionally, it can make it difficult to focus and even cause short-term memory loss because stress impacts several parts of the brain associated with memory. For example, you may have trouble remembering what you were doing just a few moments ago, which can make it difficult to focus on completing tasks or your work. It can also cause digestive issues and impact your sleep patterns by either making it difficult for you to fall asleep or cause you to feel fatigued and sleep more than you normally do.

What Types of Changes and Techniques Can Lower Your Stress Level?

It may seem simple but making sure that you are eating healthy, getting enough sleep and exercising can have a positive impact on your stress level. You should also consider making potential lifestyle changes like finding a new job if it's causing you to become overly stressed.

As far as techniques to try, Alisa says that when his patients start feeling anxious and overwhelmed by stress, he suggests reframing their focus. "Anxiety can impact the body and mind in many ways. One of the impacts it has on the brain is by causing the vision to narrow. When the brain senses danger it activates the central vision to help find an escape route. Engaging the peripheral view sends a signal to the brain, letting it know that there is no actual danger present. There are a few techniques that I use to engage in peripheral view, which then sends a trigger to the brain telling it that it's not experiencing anxiety and it's okay to regulate itself again."

Learning how to reframe your focus is important because it changes your perception of the stress you encounter so you can better manage it. Deep breathing, meditation, mindfulness, yoga, exercise, and even venting to a trusted friend can all help reduce the negative impacts stress can have on your body.

"The two most beneficial ways counseling can help manage stress is by providing an outlet and education," Alisa says. "First off, counseling can fill the void when people don't have outlets to share how they are feeling because they may be afraid of burdening someone close to them or they don't have a support system in their life.

"The second benefit is getting educated on how stress impacts the body and then learning coping mechanisms to manage triggers. In counseling, we focus on practicing awareness so you understand what may be causing you anxiety or stressors. And then once you practice awareness, you learn how to put a stop to them sooner. For example, interjecting coping strategies, whether it's breathing exercises or cognitive mental tricks, can activate the decision-making part of your brain so it can return to its normal state."

If these methods don't work or you're looking for a little more support, you can also consider contacting a practitioner about medications that can help with stress management.

This article was updated on May 3, 2022.

# data[].attributes.attachment_link.description
Stress is something that we are all aware of daily. Stress can cause bodily or mental tension. But did you know that stress can be both positive and negative? It is your perception of this stress that matters most. General adaptation syndrome is how your body responds to stress.

# data[].attributes.body
Stress causes heart rate, blood pressure, hormones, immunity, and senses go into overdrive in order to handle the perceived threat.

# data[].attributes.attachment_link.readable_text
Stress is your body's response to change. Yet the term "stress" conjures us all kinds of negative images of danger, calamity, conflicts, and difficult situations - hence the term, "distress."

But stress can also be positive: a wedding, a new job, a thrill of discovery, a vacation trip - even Christmas. Positive stress, also called " eustress," provides motivation, hope, and satisfaction.

It is as if the human body has an inner button labeled "change" that when pressed initiates a fight-or-flight response ... whether or not the stress is positive or negative.

Stress is Non-Discriminatory

What's tricky is that your body's physical reaction to change is non-discriminatory. Heart rate, blood pressure, hormones, immunity, and senses go into overdrive in order to handle the perceived threat. Your body responds to change, whether it is large or small, positive or negative.

Consider two responses to the same event. When Stephanie saw the pregnancy test results, her heart sped up and her hands become damp. She hadn't planned on this. What would she tell her family and friends? What choices would she make? Stephanie was in distress (negative stress.)

Erica's test result revealed the same results. Finally, a baby was on the way! She and her husband had been trying to become pregnant for five years. Erica felt her heart pound in her chest and then used a handkerchief to wipe her brow. She was experiencing eustress (positive stress.)

For both women, the test results represented change. Their bodies responded - one in distress and the other in eustress - in similar ways. The human body cannot tell the difference between the two kinds of stress.

What defined stress as positive or negative for Stephanie and Erica was their point of view.

In the Boat with Both Kinds of Stress

Peter experienced both positive stress and negative stress within a short time frame.

He and the disciples were in a boat when a life-threatening storm arose (negative stress: a battle with nature's elements.) Minutes later, Peter saw Jesus walking on the water towards the boat (negative stress: he mistook Jesus for a ghost; positive stress: when he recognized it was Jesus). Jesus invited Peter to walk on water (positive stress: the adventure of experiencing a supernatural feat). Peter began to sink (negative stress: fear of drowning). Jesus caught him (positive stress: rescue and relief).

Peter's stress was negative when he focused on the what - the factors creating his anxiety (the ghost and the waves.)

His stress was positive when he focused on the Who - the Person helping him deal with and overcome danger.

The kind of stress he experienced depended upon his point of view.

The Choice You Face With Stress

Every day, you're in a boat with positive stress and negative stress as your companions. Your body reacts involuntarily to stress. Your hands may shake. Your knees may knock.

But when it comes to your mind and heart, you have a choice.

What matters most is where you look. You can focus on is causing your anxiety. Or you can focus on gets you through it.

Your viewpoint makes the difference.

The choice is up to you.

More about Managing Change

Change: Is It a Pain or a Gain?

Good Grief! Can Loss Be a Gift?

The Most Common Lie About Change

# data[].attributes.attachment_link.description
Stress is your body's response to change. Yet the term "stress" conjures us all kinds of negative images of danger, calamity, conflicts, and difficult situations - hence the term, "distress." But stress can also be positive: a wedding, a new job, a thrill of discovery, a vacation trip - even Christmas.

# data[].attributes.attachment_link.readable_text
Abstract

The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. Among the factors that influenced the susceptibility to stress are genetic vulnerability, coping style, type of personality and social support. Not all stress has negative effect. Studies have shown that short-term stress boosted the immune system, but chronic stress has a significant effect on the immune system that ultimately manifest an illness. It raises catecholamine and suppressor T cells levels, which suppress the immune system. This suppression, in turn raises the risk of viral infection. Stress also leads to the release of histamine, which can trigger severe broncho-constriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries (atherosclerosis), especially if combined with a high-fat diet and sedentary living. The correlation between stressful life events and psychiatric illness is stronger than the correlation with medical or physical illness. The relationship of stress with psychiatric illness is strongest in neuroses, which is followed by depression and schizophrenia. There is no scientific evidence of a direct cause-and-effect relationship between the immune system changes and the development of cancer. However, recent studies found a link between stress, tumour development and suppression of natural killer (NK) cells, which is actively involved in preventing metastasis and destroying small metastases.

Keywords: Stress, medical illness, psychiatric illness, cancer, immune system, personality

Introduction

Stress is defined as a process in which environmental demands strain an organism's adaptive capacity resulting in both psychological demands as well as biological changes that could place at risk for illness ( 1). Things that cause us stress are called stressors. Stress affects everyone, young and old, rich and poor. Life is full of stress. Stress is an every fact of life that we must all deal with. It comes in all shapes and sizes; even our thoughts can cause us stress and make the human body more susceptible to illness. There are three theories or perspectives regarding stress; environmental stress, psychological (emotional) stress and biological stress ( 1). The environmental stress perspective emphasizes assessment of environmental situations or experiences that are objectively related to substantial adaptive demands. The psychological stress perspective emphasizes people's subjective evaluations of their ability to cope with demands presented to them by certain situations and experiences. Finally, the biological stress perspective emphasizes the function of certain physiological systems in the body that are regulated by both psychologically and physically demanding conditions.

The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. An event that causes an illness in a person may not cause illness in other person. Events must interact with a wide variety of background factors to manifest as an illness. Among the factors that influenced the susceptibility to stress are genetic vulnerability, coping style, type of personality and social support. When we are confronted with a problem, we assess the seriousness of the problem and determine whether or not we have the resources necessary to cope with problem. If we believe that the problem is serious and do not have the resources necessary to cope with the problem, we will perceive ourselves as being under stress ( 2). It is our way of reacting to the situations that makes a difference in our susceptibility to illness and our overall well-being.

Not all stress has negative effect. When the body tolerates stress and uses it to overcome lethargy or enhance performance, the stress is positive, healthy and challenging. Hans Selye ( 3), one of the pioneers of the modern study of stress, termed this eustress. Stress is positive when it forces us to adapt and thus to increase the strength of our adaptation mechanisms, warns us that we are not coping well and that a lifestyle change is warranted if we are to maintain optimal health. This action-enhancing stress gives the athlete the competitive edge and the public speaker the enthusiasm to project optimally. Stress is negative when it exceeds our ability to cope, fatigues body systems and causes behavioral or physical problems. This harmful stress is called distress. Distress produces overreaction, confusion, poor concentration and performance anxiety and usually results in sub par performance. Figure 1 illustrates this concept.

There is a growing concern about the increasing cost and prevalence of stress-related disorders; especially in relation to work place. "Worked to death, drop death, work until you drop" are highlighted "work-related death" in the 21 st century. Countries renowned for their long working hours know this well enough; Japan and China each have a word for death by overwork - karoshi and guolaosi respectively. Both Japan and Korea recognize suicide as an official and compensatable work-related condition ( 4). The estimated prevalence of stress and stress-related conditions in the United Kingdom rose from 829 cases per 100,000 workers in 1990 to 1,700 per 100,000 in 2001/2002. In that year, 13.4 million lost working days were attributed to stress, anxiety or depression, with an estimate 265,000 new cases of stress. The latest HSE (Health and Safety Executive) analysis of self-reported illnesses rate revealed that stress, depression or anxiety affects 1.3% of the workforce ( 5). It is estimated that 80% to 90% of all industrial accidents are related to personal problem and employees' inability to handle stress ( 6). The European Agency for Safety and Health at work reported that about 50% of job absenteeism is caused by stress ( 7).

The morbidity and mortality due to stress-related illness is alarming. Emotional stress is a major contributing factor to the six leading causes of death in the United States: cancer, coronary heart disease, accidental injuries, respiratory disorders, cirrhosis of the liver and suicide. According to statistics from Meridian Stress Management Consultancy in the U.K, almost 180,000 people in the U.K die each year from some form of stress-related illness ( 7). The Centre for Disease Control and Prevention of the United States estimates that stress account about 75% of all doctors visit ( 7). This involves an extremely wide span of physical complaints including, but not limited to headache, back pain, heart problems, upset stomach, stomach ulcer, sleep problems, tiredness and accidents. According to Occupational Health and Safety news and the National Council on compensation of insurance, up to 90% of all visits to primary care physicians are for stress-related complaints.

Stress and the immune system

Our immune system is another area which is susceptible to stress. Much of what we know about the relationship between the brain, the nervous system, and the immune response has come out of the field of psychoneuroimmunology (PNI). PNI was developed in 1964 by Dr. Robert Ader, the Director of the Division of Behavioral and Psychosocial Medicine at the University of Rochester. Psychoneuroimmunology is the study of the intricate interaction of consciousness (psycho), brain and central nervous system (neuro), and the body's defence against external infection and aberrant cell division (immunology) ( 8). More specifically it is devoted to understanding the interactions between the immune system, central nervous system and endocrine system. Although a relatively new medical discipline, the philosophical roots of the connection between physical health, the brain and emotions can be traced to Aristotle.

Immune responses are regulated by antigen, antibody, cytokines and hormones. Lymphocytes are most responsible for orchestrating the functions of the immune system. The immune system has about 1 trillion lymphocytes. Lymphocytes that grow and mature in the thymus are called T cells; other lymphocytes are called B cells. B cells secrete antibodies, chemicals that match specific invaders called antigens (humoral immunity). T cells do not secrete antibodies but act as messengers and killers, locating and destroying invading antigens (cellular immunity). Some T cells, called helpers, help activate the production of other T and B cells. Other T cells, called suppressors, stop the production of antigens, calling off the attack. The number of T and B cells must be balanced for them to perform effectively. When the ratio of T to B cells is out of balance, the immune response is compromised and does not work effectively. Other key chemicals that are produced by the immune systems are macrophages, monocytes and granulocytes. These chemicals envelop, destroy and digest invading microorganisms and other antigens. Known generally as phagocytes, they team up with more than 20 types of proteins that make up the immune system's complement system. This system is triggered by antibodies that lock onto antigens, which cause inflammatory reactions.

Cytokines are non-antibody messenger molecules from a variety of cells of the immune system. Cytokines stimulate cellular release of specific compounds involved in the inflammatory response. They are made by many cell populations, but the predominant producers are helper T cells (Th) and macrophages. Th1 and Th2 cytokines inhibit one another's production and function: Th1 cells stimulate cellular immunity and suppress humoral immunity, while Th2 cytokines have opposite effect. Cytokines is a general name; other specific name includes lymphokines (cytokines produced by lymphocytes), chemokines (cytokines with chemotactic activities), interleukin (IL) (cytokines made by one leukocyte and acting on other leukocytes) and interferon (IFN) (cytokines release by virus-invaded cell that prompt surrounding cell to produce enzymes that interfere with viral replication).

Cytokines are produced de novo in response to an immune stimulus. They generally act over short distances and short time spans and at very low concentration. They act by binding to specific membrane receptors, which then signal the cell via second messenger, often tyrosine kinases, to alter its behaviour (gene expression). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokines receptors), proliferation and secretion of effectors molecules. The largest group of cytokines stimulates immune cell proliferation and differentiation. Some common bacterial antigens activate complement and stimulate macrophages to express co-stimulatory molecules. Antigens stimulate adaptive immune responsiveness by activating lymphocytes, which in turn make antibody to activate complement and cytokines to increase antigen elimination and recruit additional leukocytes.

Several studies have shown that chronic stress exerts a general immunosuppressive effect that suppresses or withholds the body's ability to initiate a prompt, efficient immune reaction ( 9, 10). This has been attributed to the abundance of corticosteroids produced during chronic stress, which produces an imbalance in corticosteroid levels and weakens immunocompetence. This weakening of immune function is thought to be associated with general strain on the various body parts associated with the production and maintenance of the immune system. For example, atrophy of the thymus or shrinking of the thymus results in its inability to produce T cells or the hormones needed to stimulate them. This can lead to an imbalance and inefficiency of the entire immune response. This is consistence with the finding that as we get elder, we are prone to suffer from infection, cancer, hypersensitivity and autoimmunity.

In a meta-analysis of 293 independent studies reported in peer-reviewed scientific journal between 1960 and 2001 with some 18,941 taking part, it is confirmed that stress alters immunity ( 11). Short-term stress actually boosts the immune system as it readies itself to meet and overcome a challenge such as an adaptive response preparing for injury or infection; but long-term or chronic stress causes too much wear and tear, and the system will break down especially if the individual has little control over events. The analyses ( 11) revealed that the most chronic stressors which change people's identities or social roles, are more beyond their control and seem endless-were associated with the most global expression of immunity; almost all measures of immune function dropped across the board. Duration of stress also plays a role. The longer the stress, the more the immune system shifted from potentially adaptive changes (such as those in fight-or-flight response) to potentially detrimental changes, at first in cellular immunity and then in broader immune function. They also found that the immune systems of people who are older or already sick are more prone to stress-related change.

The link between stress and illness

The critical factor associated with stress is its chronic effect over time. Chronic stressors include daily hassles, frustration of traffic jams, work overload, financial difficulties, marital arguments or family problems. There are, of course, many more things that can cause stress, but these are the stressors commonly encountered in daily life. The pent-up anger we hold inside ourselves toward any of these situations, or the guilt and resentment we hold toward others and ourselves, all produce the same effects on the hypothalamus. Instead of discharging this stress, however, we hold it inside where its effects become cumulative.

Research shows that almost every system in the body can be influenced by chronic stress. When chronic stress goes unreleased, it suppresses the body's immune system and ultimately manifests as illness. One can only wonder what would happen to the body if it remained in the fight-or-flight response. Fortunately, under normal circumstances, three minutes after a threatening situation is over and the real or imagined danger is removed, the fight-or-flight response subsides and the body relaxes and returns to its normal status. During this time heart rate, blood pressure, breathing, muscle tension, digestion, metabolism and the immune system all return to normal. If stress persists after the initial fight-or-flight reaction, the body's reaction enters a second stage. During this stage, the activity if the sympathetic nervous system declines and adrenaline secretion is lessened, but corticosteroid secretion continues at above normal levels. Finally, if stress continues and the body is unable to cope, there is likely to be breakdown of bodily resources.

Medical illnesses

In asthma, both external and internal factors are involved; it is the internal factor that is most affected by acute effects of psychological stressors. Family therapy is widely incorporated in the management of asthmatic children. The improvement is attributed to minimizing the interaction with parents that produced frequent stressful situation. Additionally, asthmatics exposed to a harmless substance that they thought they were allergic would elicit a severe attack ( 12). A study by Gauci et al. ( 13) demonstrated significant positive correlations between a few of Minnesota Multiphasic Personality Inventory (MMPI) distressed-related scales and skin reactivity in response to allergens. Collectively, these data provide evidence for a clear association between stress, immune dysfunction and clinical activity of atopic and asthmatic disease. For further reference, Liu et al. ( 14) provided excellent evidence that stress can enhance allergic inflammatory response.

Gastrointestinal diseases such as peptic ulcer (PU) and ulcerative colitis (UC) are known to be greatly influenced by stress. PU occurs twice as often in air traffic controllers as in civilian copilots, and occurs more frequently among air traffic controllers at high-stress centers (Chicago O'Hare, La Guardia, JFK and Los Angeles International Airport) than low-stress centers (airports in less-populated cities in Virginia, Ohio, Texas and Michigan). Although stress is a risk factor in PU, more than 20 other factors are thought to be associated as well: blood type, sex, HLA antigen type, alcoholic cirrhosis, hypertension, chronic obstructive pulmonary disease, cigarette smoking, and even consumption of coffee, carbonated beverage or milk during college ( 12). Certain stressful life events have been associated with the onset or symptom exacerbation in other common chronic disorders of the digestive system such as functional gastrointestinal disorders (FGD), inflammatory bowel disease (IBD) and gastro-esophageal reflux disease (GERD). Early life stress in the form of abuse also plays a major role in the susceptibility to develop FGD as well as IBD later in life ( 15).

Ulcers are caused by excessive stomach acid, and studies of patients with gastric fistulas have shown that anger and hostility increase stomach acidity, while depression and withdrawal decrease it. Other theory correlating the effects of stress on the development of ulcers linked to the mucous coating that lines the stomach. The theory states that, during chronic stress, noradrenaline secretion causes capillaries in the stomach lining to constrict. This in turn, results in shutting down of mucosal production, and the mucous protective barrier for the stomach wall is lost. Without the protective barrier, hydrochloric acid breaks down the tissue and can even reach blood vessels, resulting in a bleeding ulcer ( 16). However, it has recently been discovered that many cases of ulcers are caused by a bacterial called Helicobacter pylori ( H. pylori) ( 17). Although the exact mechanism by which it causes ulcers is unknown, it is believed that H. pylori inflames the gastrointestinal lining, stimulates acid production or both.

Coronary Heart disease (CHD) has long been regarded as a classical psychosomatic illness in that its onset or course was influenced by a variety of psychosocial variables. Psychosocial aspects of CHD had been studied extensively and there is strong evidence that psychological stress is a significant risk factor for CHD and CHD mortality ( 18, 19, 20, 21). Tennant ( 19) found a positive relationship between life stress and cardiac infarction and sudden death; while study by Rosengren et al. ( 20) reported that CHD mortality was increased two folds for men experiencing three or more antecedent life events. The INTERHEART study ( 21) revealed that people with myocardial infarction reported higher prevalence of four stress factors: stress at work and at home, financial stress and major life events in the past year.

Although the evidences supporting an association between type A behaviour (aggressive, competitive, work-oriented and urgent behaviour) and CHD were conflicting ( 22); some studies found that type A individuals generate more stressful life events and were more likely than others to interpret encountered life event in an emotionally adverse way ( 23, 24). If type A is a risk factor it may not operate by way of long-term physiological dysfunction (leading to atherogenesis), but by way of acute life events provoking severe strain on the heart. One of the components of Type A behaviour is hostility, which may be correlated with CHD risk. Some studies ( 25, 26) noted that clinical CHD events are predicted by hostility and this seems to independent of other risk factors. Hostility was also found to be related to atherosclerosis in some angiography studies ( 27, 28). Other studies found suppression of anger was associated with CHD event ( 29) and atherosclerosis ( 27, 28). In review of these findings, Tennant ( 30) concluded that the possibility emerges that hostility (or its suppression) may have some role in CHD, although the mechanism is unclear.

The three major risk factors commonly agreed to be associated with CHD are hyper cholesterolemia, hypertension and cigarette smoking. In attempt to determine the causes of increased levels of serum cholesterol; Friedman et al. ( 31) conducted one of the early investigations of the relationship between stress and serum cholesterol. They found that stress is one of the causes of increased levels of serum cholesterol. Other researchers who studied the medical students facing the stress of exam ( 32), and military pilot at the beginning of their training and examination period ( 33) verified the findings. Since blood pressure and serum cholesterol increases during stress, the relationship between stress and hypertension has long been suspected; emotional stress is generally regarded as a major factor in the etiology of hypertension ( 34). One of the early evidence of this relationship came from the massive study of 1,600 hospital patients by Dunbar ( 35). He found that certain personality traits were characteristic of hypertensive patients; for example they were easily upset by criticism or imperfection, possessed pent-up anger and lack self-confidence. Recognizing this relationship, educational programs for hypertensive patients have included stress management.

It appears that some people are hereditarily susceptible to rheumatoid arthritis (RA). Approximately half of the sufferers of this condition have a blood protein called the rheumatoid factors (RF), which is rare in non-arthritic people. Since RA involves the body turning on itself (an autoimmune response), it was hypothesized that a self-destructive personality may manifest itself through this disease ( 16). Although the evidence to support this hypothesis is not conclusive, several investigators have found personality differences between RA sufferers and others. Those affected with this disease have been found to be perfectionists and are self-sacrificing, masochistic, and self-conscious. Female patients were found to be nervous, moody and depressed, with a history of being rejected by their mothers and having strict fathers. It has been suggested that people with the RF who experience chronic stress become susceptible to RA ( 16). Their immunological system malfunctions and genetic predisposition to RA results in their developing of the condition.

Migraine headaches are the result of constriction and dilatation of the carotid arteries of one side of the head. The constriction phase, called the prodrome, is often associated with light or noise sensitivity, irritability and a flushing or pallor of the skin. When the dilatation of the arteries occurs, certain chemicals stimulate adjacent nerve endings, causing pain. Diet may precipitate migraine headaches for some people. However, predominant thought on the cause of migraine pertains to emotional stress and tension. Feeling of anxiety, nervousness, anger or repressed rages are associated with migraine. An attack may be aborted when the individual gives vent to underlying personality ( 8). A typical migraine sufferer is a perfectionist, ambitious, rigid, orderly, excessively competitive and unable to delegate responsibility.

There is also evidence that emotionally stressful experience is associated with endocrine disorder such as diabetes mellitus ( 36). Physical or psychological stressors can alter insulin needs; stressors may often be responsible for episodes of loss of control, especially in diabetic children. Type II diabetes is most often affected by stress, as it tends to occur in overweight adults and is a less severe form of diabetes ( 12). Additionally, children who had stressful life events stemming from actual or threatened losses within the family and occurring between the ages of 5 and 9 had a significantly higher risk of type I diabetes.

Acute stress can suppress the virus-specific antibody and T cell responses to hepatitis B vaccine ( 37). People who show poor responses to vaccines have higher rate of illness including influenza virus infection. There are several other studies which demonstrated a relationship between psychological stress and susceptibility to several cold viruses ( 38, 39). This is not surprising, as stress does suppress the immune system; latent viruses then have an easier time resurging since the body cannot defend itself any more. Attempts to find an association between stress and disease progression in patients with acquired immunodeficiency syndrome (AIDS) have met with conflicting results ( 40). Analysis of the Multicentre AIDS Cohort Study failed to observe an association between depression and the decline of CD4+ T lymphocytes, disease progression or death ( 41), but others have found significant association between immunological parameters reflective of HIV progression and psychosocial factors, particularly denial and distress ( 42), and concealment of homosexual identity ( 43).

Psychiatric illness

A large body of research in the past four decades has provided evidence that recent life events contribute to the onset of psychiatric illness ( 44). The association between stressful life events and psychiatric illness is stronger than the association with physical or medical illness. Vincent and Roscenstock ( 45) found that prior to hospitalization, patients with psychiatric disorders had suffered more stressful event than those with physical disorders. Meanwhile, Andrew and Tennant ( 46) failed to find the association between stress and physical illness. Although the exact relationship between stress and psychiatric illness is not clear, the final pathway is biochemical. As with medical illness, the appropriate model is one of multifactorial causations. Most life event research indicates a limit of 6 months to consider a stress having significant effect on illness. After that, the effect of stress diminishes with time.

Recent life events held to have a major etiological role in neuroses, a formative role in the onset of neurotic depression (mixed depressive illness) and a precipitating role in schizophrenic episodes ( 47). In other words, the association of stress with psychiatric illness is the strongest in neuroses, followed by depression and schizophrenia is the least. The correlation between neuroses and schizophrenia with stress is clearer. The weak association between stressful life events and onset of psychotic illness, particularly schizophrenia had been demonstrated in a few studies ( 48, 49, 50), in contrast with strong association between stress and neuroses ( 51, 52, 53, 54). However the degree of relationship between depressive illness and neuroses in relation to stress is rather controversial. Neither Paykel ( 55) nor Brown et al. ( 56) found the relationship between life event stress and illness is greater for neurotic depression than unipolar (endogenous) depression.

Bebbington et al. ( 57) found that there is an excess of life events preceding the onset of all types of psychoses, particularly in the first 3 months. In the study of recent onset of schizophrenia, schizophreniform disorder and hypomania, Chung et al. ( 49) found that threatening life events were significantly related to the onset of schizophreniform psychosis but not schizophrenia. They also found that threatening events might precipitate hypomanic episodes. Other study ( 50) found that individuals with schizophrenia do not experience more stressful life events than normal controls, but they reported greater subjective stress. A study that investigated the relationship between recent life events and episodes of illness in schizophrenia found that, initial or early episodes of schizophrenia are more likely to be associated with recent life events than are later episodes ( 48).

On the other hand, bipolar disorders have received less study than unipolar. In bipolar disorder, the effect of life events is generally weaker than unipolar; however major life events may be important in first onset ( 58). Causative factors in bipolar disorders are multifactorial and complex, and genetic factor seems to influence life events exposure. Those with greater genetic loading, there were fewer stressful life events before the first episode and they had the earlier onset of the disease. A number of studies have shown that the onset of depression is often preceded by stressful life events ( 59, 60). Stressful life events along with recent minor difficulties have also been identified as predictors of an episode of depression in a monozygotic female twin study. Kessler ( 61) who came with the same conclusion added that there is evidence that concomitant chronic stress enhances the effect of major life events on depression.

Cooper and Sylph ( 51) documented the role of life events in the causation of neurotic illness. They found that neurotic group reported 50% more stressful events than the control group. McKeon et al. ( 52) found that patients with obsessive-compulsive neuroses who have abnormal personality traits (obsessional, anxious and self-conscious) experienced significantly fewer life events than those without such traits. Zheng and Young ( 53) in comparing live event stress between neurotic patients and normal control found that neurotic patients had significantly higher level of stress and experienced more life event changes than the control group. Rajendran et al. ( 54) who compared the neurotic executives with healthy executives as a control group, found significant differences between normal and neurotic groups in terms of the frequency of the life events as well as the stress they experienced due to those life events.

Stress and cancer

The relationship between breast cancer and stress has received particular attention. Some studies have indicated an increased incidence of early death, including cancer death among people who have experienced the recent loss of a spouse or loved one. A few studies of women with breast cancer have shown significantly high rate of disease among those women who experienced traumatic life events and loses within several years before their diagnosis. However, most cancers have been developing for many years and are diagnosed only after they have been growing in the body for a long time. Thus, this fact argues against an association between the death of a loved one and the triggering of cancer. There is no scientific evidence of a direct cause-and-effect relationship between these immune systems changes and the development of cancer. It has not been shown that stress-induced changes in the immune system directly cause cancer. However, more research is needed to find if there is a relationship between psychological stress and the transformation of normal cells into cancerous cells. One area that is currently being studied is whether psychological interventions can reduce stress in the cancer patients, improve immune function and possibly even prolonged the survival.

Studies in animals, mostly rats, revealed the link between stress and progression of cancerous tumors. Chronic and acute stress, including surgery and social disruptions, appear to promote tumor growth. It is easy to do such research in animal, but it is harder with humans. Furthermore, the interactions of many systems that affect cancer, from the immune system to the endocrine system, along with environment factors that are impossible to control for, make sorting out the role of stress extremely difficult. In addition, researchers cannot expose people to tumour cells as they do with animals. A recent study ( 62) found that there was a link between stress, tumour development and a type of white blood cells called natural killer (NK) cells. Of all the immune systems cells, NK cells have shown the strongest links to fighting certain forms of the disease, specifically preventing metastasis and destroying small metastases. Although the result of this study is not definitive, it is indicates that stress acts by suppressing NK-cell activity. Other preliminary study showed the evidence of a weakened immune system in breast cancer patients who feel high level of stress compared to those experiencing less stress.

A new study shows stress and social supports are important influences in a man's risk for developing prostate cancer. Researchers ( 63) at State University of New York at Stony Brook's medical school found men with high level of stress and a lack of satisfying relationships with friends and family had higher levels of Prostate-Specific Antigen (PSA) in their blood, a marker for an increased risk of developing prostate cancer. Based on the results, the risk of having an abnormal PSA was three times higher for men with high levels of stress. Likewise, men who had felt they had low levels of support from friends and family were twice as likely to have an abnormal PSA. The findings raise the possibility that a man's psychological state can have a direct impact on prostate disease.

References

5. 2003. Self-reported work-related illness in 2001/02: Results from a household survey, (SW 101/02), HSE,

6. Jansen M. Emotional disorders in the labour force: Prevalence, costs, prevention and rehabilitation. Internat Labour Rev. 1986;125:605-15. [ Google Scholar]

10. Huebner HS. Burnout among school psychologists: An exploratory investigation into its nature, extent and correlates. School Psychol Quart. 1992;7:129-36. [ Google Scholar]

11. Segerstrom SC, Miller GE. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130:601-30. [[ PMC free article] [ PubMed] Google Scholar]

17. European [[ Helicobacter pylori study group Current European concepts in the management of H. pylori information: The Maastricht Consensus. Gut. 1997;41:8-13. PMC free article] [ PubMed] Google Scholar]

20. Rosengren A, Orth Gomer K, Wedel H, Wihelsem L. Stressful life events, social support and mortality in men born in 1933. Brit Medi J. 1993;307:1102-5. [[ PMC free article] [ PubMed] Google Scholar]

54. Rajendran K, Rao VN, Reddy MV. A profile of stressful life events among industrial neurotics and normal. NIMHANS Journal. 1996;14:127-132. [ Google Scholar]

Articles from The Malaysian Journal of Medical Sciences : MJMS are provided here courtesy of School of Medical Sciences, Universiti Sains Malaysia

# data[].attributes.attachment_link.description
The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. Among the factors that influenced the susceptibility to stress are genetic vulnerability, coping style, type of personality and social support. ...

# data[].attributes.body
Many medicines work by targeting the chemicals your body uses to control its processes.

Sometimes, the same chemical may control more than one process, or a medicine may affect more than one chemical.

E.g beta blockers block the release of the stress hormones. This slows the heart rate down and can also lower blood pressure. This means they can be a useful way to lower blood pressure, but if your blood pressure is already normal and you’re taking it to control your heart rate or angina, the blood-pressure-lowering effect may lead to dizziness.

It may also be that a particular ingredient doesn’t suit you, or your medication could be interacting with other medication or supplements you take.

There is also lot of research to show that if we expect to get a side effect, we will. This is called the “nocebo effect”.

# data[].attributes.attachment_link.title
Medication side effects: how to deal with them

# data[].attributes.attachment_link.description
Our Senior Cardiac Nurse shares expert tips for adjusting to new medications.

# data[].attributes.body
Different types of drugs can affect your body in different ways, and the effects can vary.

How a drugs affect an individual is dependent on:

body size

general health

the amount and strength of the drug

whether any other drugs have been taken around the same time.

a person’s mood or the environment they are in.

The effects can be physical and psychological.

Drugs can impact the way you think, feel and act.

Reasons for drug use:

People use drugs for many reasons, these reasons might include to:

Feel good

Relax

Cope with stress, anxiety, depression, emotional pain or a history of trauma

Experiment

Stay awake

Fall asleep

Enhance social experiences

Drugs affect the body's central nervous system, how a person thinks, feels and behaves.

The seven main types: depressants, psychedelics, stimulants, empathogens, opioids, cannabinoids, and dissociatives.

Depressants - slow down the messages travelling between the brain and the body. Reduce arousal and stimulation, making a person feel relaxed or drowsy.

Psychadelics - affect all the senses, altering thinking, sense of time and emotions. They can cause hallucinations.

Stimulants - Drugs that speed up messages travelling between the brain and body. Make a person feel more awake, alert, confident or energetic.

Empathogens - Increase a person’s feeling of empathy and kindness towards others.

Opioids - Any drug that acts on opioid receptors in the brain, and any natural or synthetic drugs that are made from or related to the opium poppy. Slow heart rate and breathing and provide sensations of pleasure and pain relief.

Cannabanoids - chemical compounds found in all parts of the cannabis plant. They have a psychoactive effect and can make a person feel happy, relaxed, anxious or paranoid.

Dissociatives - cause people to feel separated or detached from reality, hallucinations or other changes in thoughts, emotions and consciousness.

Drugs can cause...

Taking part in risky behaviours such as drink driving or unprotected sex.

Changes in behaviour/ mood swings/ increased aggression.

Impact on sleep/insomnia.

Cognitive/memory problems.

Reduced appetite.

Regular colds/flus.

Long term health impacts - liver, kidney and heart problems. Cancer (depending on the type of drug used and how frequently it was used)

Cavities and gum disease

Mental health issues such as anxiety and depression

Dependence

Overdose

Psychosis

Infectious disease from shared injecting equipment

Damage to veins from unsafe injecting practices

Financial, work or social problems.

Effects of certain drugs:

Cannabis:

Relaxation and altered perception.

increased heart rate/blood pressure.

Relaxed and happy.

Lethargy, anxiety, paranoia, and psychosis in extreme cases.

Mental health problems - such as schizophrenia

When smoked - lung diseases such as asthma chronic bronchitis and lung, throat,tongue and mouth cancer.

How your brain works - concentration.

Reduces your fertility

Cocaine:

Increased energy.

Makes you feel happy, awake, confident and less inhibited.

Overstimulates the heart and nervous system - can lead to a seizure, brain haemorrhage, stroke or heart attack.

Reduces your pain perception and may result in injury.

Carries greater risk if mixed with alcohol or other stimulants.

Harms your baby during pregnancy, may cause miscarriage.

Increases the risk of mental health issues such a s anxiety, paranoia and psychosis.

If snorted, can cause damage to the lining of the nasal passage and nose.

If injected, can cause vein collapse and increased risk of HIV and hepatitis infection.

Ecstacy:

Alert, warm and chatty.

Can make sounds and colours seem more intense.

May cause anxiety, confusion, paranoia and even psychosis.

Is linked to memory loss, depression and anxiety

Can lead to overheating and dehydration

Tends to stop your body producing enough urine, so your body retains fluid.

Effects of a drug comedown:

Feeling anxious, depressed or irritable.

Tiredness.

Shaky.

Dizzy.

Sweaty.

Headaches.

Nauseous.

Lack of appetite.

Sleepy or unable to sleep.

# data[].attributes.attachment_link.description
Drugs affect your body’s central nervous system. They affect how you think, feel and behave.

# data[].attributes.body
Can cause hallucinations and other risky effects.

Can be used for therapy.

They change or enhance sensory perceptions, thought processes, and energy levels.

They are used in religious ceremonies to experience spiritual or heightened states of awareness.

Psychedelics are used in psychology and psychiatry as a viable way to treat anxiety, depression, PTSD, and more.

Psychedelics do not appear to be addictive.

Some may lead to tolerance and some people report experiencing withdrawal effects when they stop.

The effects of Psychedelics:

Altered perception of time

Difficulty communicating

Feeling sensations, hearing sounds, and/or seeing images that aren't real

Increased energy

Heightened awareness/understanding

Nausea

Spiritual experiences

Vivid sensory experiences

Certain drugs and their affects:

LSD - Increase in heart rate/ increase in body temp/dizziness/sleepiness/increased blood pressure/loss of appetite/dry mouth/sweating/numbness/weakness/tremors/ impulsive behavior.

Peyote - Increase in heart rate/increase in body tempuncoordinated movements/excessive sweating/ flushing.

DMT - Increase in heart rate/agitation and body distortions.

Psilocybin - Feelings of relaxation or introspection/ nervousness/ paranoia and panic.

# data[].attributes.attachment_link.description
Psychedelic drugs (hallucinogens)—chemicals such as LSD and plants such as peyote and magic mushrooms. While generally not addictive, there are other serious risks.

# data[].attributes.body
Side effects of Psychiatric medication:

This side effects you depend on which medication you take and your individual reaction to it.

Some people get certain side effects while others don't.

If you do get side effects, they could be mild or severe.

Side effects of antidepressants:

SSRIs and SNRIs (impact the amount of serotonin in your body or both serotonin and norepinephrine)

Headaches.

Decreased alertness.

Nausea.

Sexual problems.

Tooth decay.

Diabetes.

SIADH.

Gatstrointestinal bleeding.

Serotonin syndrome.

Suicidal feelings.

Neuroleptic malignant syndrome.

Hypomania/mania.

Tricyclicsan ( an older type of antidepressant but can be more dangerous if an overdose is taken. They cause more unpleasant side effects than SSRIs and SNRIs) :

Antimuscarinic effects.

Tooth decay.

Decreased alertness.

Suicidal feeling.

Serotonin syndrome.

SIADH.

Diabetes.

Neuroleptic malignant syndrome.

Hypomania/mania.

MAOIs - ease depression by affecting neurotransmitters used to communicate between brain cells, they include isocarboxazid, phenelzine, selegiline, and tranylcypromine.

Decreased alertness.

SIADH.

Suicidal feeling.

Serotonin syndrome.

Diabetes.

Neuroleptic malignant syndrome.

How do these side effects affect me?

Antimuscarinic effects - side effects caused by changes to the level of the chemical acetylcholine in your body.

If your level of acetylcholine changes, this can have effects all over the body. These effects include:

Blurred vision.

Confusion and agitation.

Constipation.

Difficulty urinating.

Drowsiness.

Dry mouth/ tooth decay.

Erectile dysfunction.

Hallucinations.

Hot or dry skin, and decreased sweating.

Increased pressure in the eye.

Low blood pressure (taking hot baths increases this risk).

Nausea.

Rapid heartbeat and disturbed heart rhythm.

Decreased alertness - Antidepressants can make you feel less alert or able to concentrate. This can happen especially when you first start taking them. This may affect your ability to drive and to do other skilled tasks.

Diabetes - Long-term use of antidepressants over several years may increase your risk of diabetes. This is especially in people who are:

Over the age of 30.

Taking SSRIs or tricyclics.

Gastrointestinal bleeding - A rare side effect of some SSRI antidepressants is bleeding inside your gastrointestinal system, which includes your stomach and intestines. The risk of gastrointestinal bleeding is higher for older people. If you are over 80, your doctor may prescribe you a different antidepressant to avoid this risk.

Hypomania or mania - This may stop if you stop taking the antidepressant. But sometimes it may be a sign of Bipolar disorder.

Neuroleptic malignant syndrome - NMS is a rare neurologic disorder, which means it affects your nervous system.

It is a side effect of antipsychotic drugs. But it can sometimes happen with antidepressants. It usually develops rapidly over 24 to 72 hours.In rare cases, it can be fatal.

Symptoms:

Sweating or fever, with a high temperature.

Tremor (shaking), rigidity (feeling stiff and unable to move your muscles) or loss of movement.

Difficulty speaking and swallowing.

Rapid heartbeat, very rapid breathing and changes in blood pressure.

Changes in consciousness, including confusion, lethargy or going into a coma.

# data[].attributes.attachment_link.readable_text
Tell us more

What do you want to tell us about?

Note:

Please don't include personal details like your name or email address. If you do, data protection law means we'll have to delete your comments.

Unfortunately we can't reply to this. If you want a response from us, see our Contact us page.

If you are in crisis right now and want to talk to someone urgently then you could call Samaritans on 116 123 (freephone). Our pages on crisis services have more options.

# data[].attributes.attachment_link.description
Tell us more What do you want to tell us about? Note: Please don't include personal details like your name or email address. If you do, data protection law means we'll have to delete your comments. Unfortunately we can't reply to this. If you want a response from us, see our Contact us page.

# data[].attributes.attachment_link.readable_text
Abstract

The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of experimental, observational, and epidemiological studies have investigated the use of SSRIs and their association with suicidality. Taking account of the methodological limitations of these studies, the current evidence fails to provide a clear relationship between their use and risk of suicidality in adults. However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides. This risk can be anticipated and managed clinically. Clinicians are, therefore, advised to maintain a close follow-up during the initial treatment periods and remain vigilant of this risk. This advisory, however, should not deter clinicians from the use of effective dosages of antidepressants for a sufficient period of time, in every age group of patients, when clinically needed, and if found suitable otherwise.

Keywords: Antidepressant, Depression, Risk of SSRIs to children and adolescents, Selective Serotonin Reuptake Inhibitors, Suicidality, Suicide

Introduction

Debate persists on whether some antidepressant drugs (ADs), in particular the Selective Serotonin Reuptake Inhibitors (SSRIs), cause the emergence or worsening of suicidal ideas in vulnerable patients. Across the globe, ADs, especially SSRIs, are among the most commonly prescribed medications (Stafford, 2001[ 26]). Large amounts of prescriptions are written because of the perception and knowledge that they are largely safe and effective across a wide variety of common disorders, namely depression and anxiety disorders. Concerns related to safety were initially raised in the early 1990s, with reports that described a possible association with suicidality (Teicher et al., 1990[ 28]), and from time to time later (Healy, 2004[ 11]). However, inferences regarding the plausibility and strength of the association between suicidality and the use of SSRIs have been conflicting and inconclusive (Khan et al., 2000[ 15], 2003[ 16]; Simon et al., 2006[ 24]).

In recent times, in order to get more information on the issue, many different study designs, including randomized clinical trials, observational studies, and ecological time trend analyses have been performed. Each of these research designs, with their unique strengths and limitations, have contributed by generating information that may be used to guide clinical practice patterns.

We summarize the current evidence, to generate evidence-based suggestions, for day-to-day clinical work. We have adopted a descriptive view of data presentation in this article to elucidate the relevant findings and produce useful clinical insights into this highly conflicting issue.

Ecological Studies

Ecological analyses have investigated whether the increasing use of SSRIs is associated with benefits in terms of decreasing rates of suicide. Evidence that antidepressants and other interventions offered by mental health professionals yield the expected reductions in risk of suicides or attempts is mixed (Singh, 2004[ 25]). Correlative pharmacoepidemiological studies have compared suicide rates by regions or years with the concurrent rates of prescriptions for antidepressants (Baldessarini and Tonda, 2007[ 3]). Several studies in US and Nordic countries (Scandinavian countries of northern Europe) have shown that emergence of modern, less toxic antidepressants, over the past decade, which dominate the current clinical practice, was associated with a generally moderate decrease in the overall suicide rates, varying in sex and age groups. Isacsson, 2000,[ 12], analyzed national statistics on suicide, alcohol consumption, unemployment, and the use of Ads, for the period 1978 - 1996, in Sweden, Denmark, Norway, and Finland. The study reported a reduction in suicide rates by 19%, in parallel with the increased use of ADs in these countries. However, in women under the age of 30 and over 75 years, the suicide rates remained unchanged, despite an increased consumption of ADs. Overall, Isacsson[ 12] concluded that the increased use of ADs appeared to be one of the contributing factors to the decrease in suicide rate.

However, evidence also suggests that similar trends of reduction in suicide rates were observed at least a decade ago, before the introduction of the first SSRI, Fluoxetine, in the US market and in some Nordic nations (Reseland et al., 2006[ 21]). This suggests that many other factors were also operational in the reduction of suicide rates in these nations. Baldessarini and Tonda, 2007,[ 3], reported that only nine of the 29 ecological studies found significant inverse correlations of the increased use of modern antidepressants with diminishing national, regional or temporal trends in suicide rates; another 14 studies found correlations in some sex or age subgroups, who were inconsistent across the studies; and six found no significant relationships. Same analysis of the data from 78 reporting countries indicated that about half (54%) experienced a decrease in annual suicide rates between the 1950s (when antidepressants were not available) and early 2000s (a decade after the introduction of modern antidepressants); and a similar proportion (46%) reported an increase. Moreover, both types of changes have been reported from similar world regions, including a decrease and increase in Western and Eastern Europe, Latin America, and Asia. These outcomes suggest random or at least highly complex phenomena, likely to reflect the impact of many contributing factors.

Studies looking for suicide rates in a specific age group have shown different results. Pharmacoepidemiological data from the US suggest that paralleling the widespread use of SSRIs, the suicide rates among those aged 15 - 19 years fell from 11 / 100,000 in 1990 to 7.3 / 100,000 in 2003; and synchronous with the US FDA black box warning on antidepressants and the likely reduction in antidepressant usage in 2004, the suicide rates climbed to 18 for those younger than 20 years - from 1,737 to 1,985 deaths (Hamilton et al.,2005[ 9]).

Results of such ecological studies are influenced by a variety of factors, like improvement in public health, changes in legal, cultural or social prohibitions against suicide, improvement in identifying and reporting suicides, and increased access of more people to modern antidepressants (Barbui et al.,2007[ 4]). Tonda et al.,2006[ 30], found a strong correlation between state suicide rates and economic and demographic measures, likely to be associated with access to clinical care in general, including population density, clinician / 100,000 population, per capita income, access to medical insurance, and public support of mental health services. Although such studies may suggest hypothesis to be tested by more sophisticated measures, they cannot prove a direct, casual relationship between antidepressant treatment and reduced risk of suicide at the level of individuals.

Barring a few studies, the ecological studies in general, suggest the possible benefits of ADs exposure in the needy population. It is also important to emphasize that all ecological studies suffer from a fundamental inability to relate antidepressant exposure to suicidal behavior, at the level of the individual.

Case Control and Cohort Studies / Observational Studies

Observational evidence is present from large cohorts of depressed patients from general practice or the health maintenance organizations' data source and from the relatively large case control comparisons of subgroups, varying in exposure to antidepressants. Olfson et al., 2006,[ 19] in a matched case-control study, estimated the relative risk of suicide attempts and suicidal deaths in severely depressed children and adults treated with ADs versus those not treated with AD drugs. In these high-risk patients, AD drug treatment did not seem to be related to suicide attempts and deaths in adults, but it might be related in children and adolescents. Juurlink et al., 2006,[ 14] studied population-based coroner's records and found that during the first month of therapy, SSRI use was associated with a nearly five-fold higher risk of completed suicide than other ADs. However, the absolute risk was low in comparison to untreated patients. This suggests that an idiosyncratic response to SSRIs may provoke suicide in a vulnerable subgroup of patients.

Simon et al., 2006,[ 24] assessed the suicide risk during antidepressant treatment by computerized health plan records and identified around 65,000 individuals with 82,000 episodes of AD treatment. The study did not suggest significant increased risk of suicide or serious suicide attempts after starting treatment with newer AD drugs.

Martinez et al., 2005,[ 18] conducted a nested case-control study based on information extracted from the General Practice Research Database, and analyzed the risk of non-fatal self-harm and suicide in patients with a new diagnosis of depression, who were prescribed SSRIs or tricyclics. The cohort included 146,095 patients. Patients taking SSRIs were not at an increased risk of suicide or non-fatal self-harm. However, in patients aged 18 years or less, weak evidence indicated a higher risk of non-fatal self-harm.

Isacsson et al., 2005,[ 13] adopting a different approach, analyzed detection of different ADs in the forensic toxicological screening of 14,857 suicides compared to 26,422 cases of death by natural or accidental causes in Sweden from 1992 to 2000. This analysis did not support the increased risk of suicidality following AD treatment in Sweden over a period of nine years.

Interpretation of finding from these studies is significantly compromised by the risk of 'confounding by morbidity or by indication.' That is, medical treatment in general is more likely to be sought and given to more severely ill patients at a higher risk of suicide, and lesser toxic drugs are likely to be selected for patients at an increased risk for suicide. The non-randomized, clinically selected treatment in such studies can severely distort the observed associations between a greater suicide risk and use of particular treatments. Although many studies statistically adjusted for this possible confounder, the possibility that other known and unknown variables might have acted in unpredictable ways, cannot be ruled out. However, these studies do not provide information about any risk of suicidality with ADs in adults with depression. The need for more supervision in children and adolescents regarding suicidality subsequent to exposure of ADs is advised.

Randomized Controlled Trials

Randomized Controlled Trials (RCTs) should be the best source of data on the effects of antidepressant treatment on suicidal risks, and hundreds of RCTs support the licensing and clinical utility of ADs in a variety of psychiatric disorders. Several systemic reviews and pooled analysis of RCTs have evaluated this issue.

Fergusson et al., 2005,[ 7] reviewed all published 702 RCTs, which included 87,650 patients, comparing SSRIs with placebo or other antidepressants. Almost a two-fold increase in the odds of suicidal attempts, but not in completed suicides, in SSRI users, was found compared to placebo or other therapeutic interventions. However, no difference was observed when a comparison between SSRIs and TCAs was made. Some serious limitations to this review were present, most important being lack of any information on adverse events for 58% of the patients eligible for analysis. Many other meta-analyses had also found an overall greater risk with antidepressants (Tollefson et al., 1994[ 29], Khan et al., 2000[ 16], 2003[ 15]; Storosum et al., 2001[ 27]).

In contrast, Gunnell et al., 2005[ 8], reviewed both published and unpublished randomized trials submitted by pharmaceutical companies to the safety review of the Medicine and Healthcare products Regulatory Agency (MHRA), pn depression and other clinical conditions. The outcome measures were completed suicide, non-fatal self-harm, and suicidal thoughts. This study reported no evidence of an increased risk of completed suicide, weak evidence of increased risk of self-harm, and inconclusive evidence of an increased risk of suicidal thoughts, with estimates compatible with modest protective or adverse effects.

The largest of these analyses was recently organized by the US Food and Drug Administration (FDA) to review all available data from 386 controlled trials of modern antidepressants involving 112,875 patient-subjects with major depressive or other disorders (Laughren, 2006[ 17]). This found no overall difference in the risk of 'Suicidality' (mainly suicidal ideation). However, on performing a secondary analysis by age-stratified measures, they suggested a differential risk of antidepressant-induced suicidality across the age spectrum, with a greater risk at the younger end of the spectrum, and a declining risk with aging, and perhaps even a protective effect in the elderly.

Concerns over safety of the use of SSRIs in children and adolescents have become paramount following the extensive review by British and American regulatory agencies. Hammad et al., 2006[ 10], in a review of both published and unpublished clinical trials using SSRIs in children and adolescents with depression and other indications (N > 4,400 subjects, across 26 controlled trials, 16 of them for depression), revealed an increased risk of new onset suicidal ideation between SSRI- and placebo-treated individuals (occurring at the respective rates of 4 and 2%, for a risk ratio of 1.95). However, all reported events refer to suicidal ideation rather than suicidal acts or completed suicide.

Trials of ADs in adults have found a substantially larger reduction in the average rating of suicidal ideations with AD than placebo (Pedersen, 2005[ 20]; Acharya et al.,2006[ 1]). However, these findings were based on post hoc analysis of individual items on standard depression symptom rating scales (HAM-D, MADRS), which could shift coincidently with overall clinical improvement. Studies with ADs that explicitly considered suicidal ideation and behavior as outcome measures remain to be carried out.

Randomized Controlled Trials have limitations that can lead to uncertainties and artefacts. These include potentially unreliable, incidental, passive reporting of suicidal thoughts or behaviors in most RCTs, based on conditions not designated explicitly to detect suicidal events. The short-term bases of most clinical trials for acute depression also do not provide an adequate basis of evaluating the effect of ADs on rare suicidal behavior. Much of the reported events involve suicidal ideation of highly uncertain clinical significance and quantitatively very limited relationship to actual life-threatening behavior. In the placebo arm, the dropout rates are significantly higher owing to perceived lack of treatment efficacy, which can limit observable suicidal risk in the placebo arm, leading to an interpretation that active treatment is 'riskier' than placebo. Although procedure of pooling data from a large number of trials increases the overall sample, the absolute number of patients attempting or committing suicide remained low. This leaves a possibility that even reporting or not reporting a few cases could have completely changed the overall outcome (Cipriani et al.,2005[ 5]). Reduction in risk might not be observed as readily over short time periods, or in studies in which suicidality was used as an exclusion criterion.

The preceding findings have been widely debated and have created a huge attention of the lay media and public to this issue. Responding to this, the US FDA recommended revision of drug manufacturers' information bulletins to include a highlighted 'Black Box' warning of the risk for possible emergence of suicidality.

Therefore, data pooled from relatively brief, randomized controlled trials in acute major depression in the young and elderly adults fail to suggest the risk of suicidality. In children and adolescents, few vulnerable cases may experience increase in suicidal ideations at the start of treatment. Hence, a clinician should routinely assess the risk and benefit ratio of an individual case, before prescribing ADs for them.

Discussion

Possible reasons why ADs might increase the risk of suicide are discussed herewith.

Antidepressant therapy typically involves a substantial delay before clinically obvious improvements occur. During initial, partial recovery, it is possible that suicidal impulses as well as the energy to act on them may increase. Patients should be forewarned of this likely delay in treatment effects, should be given encouragement and monitored especially closely in the initial days and weeks of treatment. If full response to treatment is not observed, adjustments in medication dosage, or a change to a different antidepressant, may be necessary.

Heterogeneity in the psychopharmacological effects of SSRIs suggests that some patients might experience a worsening of mood with SSRI treatment. Undiagnosed bipolar disorder, especially Type II, may be present in patients presenting with depression. Recent studies suggest that antidepressants might worsen the mood in patients with undiagnosed bipolar disorder (Baldessarini et al., 2006[ 2]) and may cause agitation and impulsivity, and exacerbate psychosis, resulting in an increased risk of suicide. If such symptoms emerge during the course of treatment of depression, the ADs should be stopped and appropriate treatment for Bipolar Disorder started.

Pharmacotherapy of mild depression is under greater scrutiny and should be decided on a case-to-case basis. Higher risk in children and adolescents should encourage clinicians to be more cautious in their management: they should resort to pharmacotherapy only after considering the risk / benefit ratio in each patient. Guidelines from the US FDA and American Academy of Child and Adolescent Psychiatry (AACAP) call for intensive monitoring during the early phase of treatment: as often as weekly for the first four weeks, fortnightly for the next month, and monthly thereafter (FDA, 2007[ 6]; Rey and Martin, 2006[ 22]). However, concerns have been raised that such guidelines may deter some clinicians from using ADs if they are unable to provide such monitoring, especially in underserved areas, and thus deserving patients may be denied the right treatment (Scahill et al., 2007[ 23]).

Conclusions [See also Figure 1 : Flowchart of Paper]

Understanding the effects of SSRI antidepressants on suicide is important for government regulators as well as for doctors, patients, and the family and friends of those suffering from illnesses requiring AD treatment. Taking into account available evidence, and limitations of the evidence available, following insights for clinical practice can be highlighted:

Available evidence is in favor of effectiveness of these agents in many clinical conditions; so clinicians should prescribe effective dosage of medications to those in need.

The current evidence fails to conclusively establish a relationship between increased suicidal ideation and behavior after use of AD medications. At best it suggests some increased risk for children and adolescents.

Clinicians should be aware of the fact that both TCAs and SSRIs may induce or cause worsening of suicidal ideations; hence, there is a need for early follow-up and encouraging support and supervision of patients, especially in the early phase of treatment.

However, this adverse effect can usually be anticipated and identified clinically, and treatment can be appropriately modified in time, such as, offering greater psychological support, removing ADs, adding anxiolytics, antipsychotics or mood-stabilizing agents, as may be deemed necessary.

Take home message

1. Caution is advisable during prescription of antidepressants to patients, especially in children and adolescents, as it may precipitate suicidal ideation in some vulnerable patients.

2. However, this can be readily identified and managed clinically, and it should not deter clinicians from providing effective pharmacological treatment to those in need.

Questions that this Paper Raises

1. What are the reasons for the age-wise distribution of change in suicidality subsequent to exposure to antidepressants, in patients with depression?

2. Is there a deferential risk of antidepressants for increased suicidality in children and adolescents? What is their relative risk?

3. What are the determinants of increased suicidal risk in these patients?

4. Do ADs reduce suicidal ideation, attempts, or completed suicides in patients?

About the Author

Dr. Anil Nischal currently holds the position of Associate Professor of Psychiatry at the CSM Medical University (Erstwhile King George's Medical College), Lucknow, UP, India. He completed his MD in psychiatry in 2000, from KGMC and has worked at various institutions, including Institute of Human Behavioral and Allied Sciences, New Delhi; Lady Harding Medical College, New Delhi; Dr. RML Hospital, New Delhi, and the Himalayan Institute of Medical Sciences, Dehradun. He has also worked with the Royal College of Psychiatry, UK, and has been involved with the preparation of the Hindi adaptation for various patient information leaflets of that College. He has about 15 national and international publications and two book chapters to his credit. His main areas of interest are Anxiety Disorder, Stress Management, and burden of care of Psychiatric Disorders.

About the Author

Dr Adarsh Tripathi is MD in Psychiatry and currently working as an Assistant Professor in Psychiatry at the C.S.M. Medical University, Lucknow, India. He has more than 25 national and international publications and four book chapters to his credit and has worked in six international and national researches of repute. His areas of interest include Addictions, Bipolar Disorder, Cognition, Adult ADHD, and Psychopharmacology..

About the Author

Dr Anuradha Nischal is currently working as an Associate Professor in Pharmacology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, India. She has been associated with institutions like the Lady Harding Medical College, New Delhi; Institute of Human Behavior and Allied Sciences, New Delhi; Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India. With the learning and experiences at these places, she has written a book Viva questions in pharmacology for the benefit of students (published 2011). She has eight national and international publications to her credit. She has supervised and co-supervised various MD and PhD theses. Her chief area of interest is Neuro-Psychopharmacology.

About the Author

Dr. Jitendra Kumar Trivedi is a Professor in the Department of Psychiatry, Chhatrapati Shahuji Maharaj Medical University, U.P., (formerly King George Medical University, Lucknow) India. He has been a member of The Royal College of Psychiatrists, U.K. since 2005. He has been the Fellow member of the American Psychiatric Association since 2007, and nominated Honorary Member of the World Psychiatric Association in 2008, and Fellow of the National Academy of Medical Sciences. He has been a principal investigator for more than 25 multinational clinical trials as well as ICMR and WHO sponsored projects. He has around 240 publications in national and international Journals as well as chapters in books. He has been an Editor, in the Indian Journal of Psychiatry, President of the Indian Psychiatric Society, and a Zonal Representative for Southern Asia - Zone-XVI of the World Psychiatric Association. He is Vice President, Indian Association for Social Psychiatry; Chairperson, Ethics Committee, IPS, and has been a member of the International Advisory Committee for the 2011 ISSPD Congress. He has also been Advisor, SAARC Psychiatric Federation, and Editor, Journal of SAARC Psychiatric Federation (2007 - 2008).

Footnotes

Conflict of interest: None declared
Declaration
This is our original unpublished work, not under consideration for publication elsewhere.

CITATION: Nischal A, Tripathi A, Nischal A, Trivedi JK. Suicide and Antidepressants: What Current Evidence Indicates. Mens Sana Monogr 2012; 10: 33-44.

References

3. Baldessarini RJ, Tondo L. Psychopharmacology of suicide prevention. In: Tatarelli R, Pompili M, Girardi P, editors. Suicide in Psychiatric disorder. New York: Nova Science Publications; 2007. pp. 193-213. [ Google Scholar]

4. Barbui C, Cipriani A, Tansella M. Beneficial and adverse effects of antidepressants on suicide mortality in individuals with major depression. In: Tatarelli R, Pompili M, Girardi P, editors. Suicide in Psychiatric disorder. New York: Nova Science Publications; 2007. pp. 19-35. [ Google Scholar]

11. Healy D. Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression. New York: University Press; 2004. [ Google Scholar]

23. Scahill L, Oesterheld JR, Martin A. General principles, specific drug treatment and clinical practice. In: Martin A, Volkmar FR, editors. Lewis's Child and Adolescent Psychiatry. 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2007. pp. 754-89. [ Google Scholar]

Articles from Mens Sana Monographs are provided here courtesy of Wolters Kluwer -- Medknow Publications

# data[].attributes.attachment_link.title
Suicide and Antidepressants: What Current Evidence Indicates

# data[].attributes.attachment_link.description
The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, ...

# data[].attributes.attachment_link.title
How do antidepressants work? - Neil R. Jeyasingam

# data[].attributes.headline
Natural supplements as powerful as drugs

# data[].attributes.subject
Natural supplements as powerful as drugs

# data[].attributes.attachment_link.readable_text
Most supplements haven't been proven to be effective, and some may not benefit you at all.

Still, there are exceptions. In fact, some supplements are comparable to pharmaceutical drugs.

Here are 4 natural, health-boosting supplements that are as powerful as drugs.

Berberine is a bioactive substance extracted from certain plants.

It isn't well known but may be one of the most powerful supplements on Earth.

It provides various health benefits but is particularly effective at lowering blood sugar levels ( 1).

These effects are thought to be due to numerous mechanisms. In particular, berberine is believed to reduce glucose production in your liver and improve insulin sensitivity (, ).

Studies show that taking berberine can lower blood sugar levels to a similar extent as the popular diabetes drug metformin ().

In a study in 116 people with type 2 diabetes, the substance reduced fasting blood sugar levels by 20% and HbA1c (a marker for long-term blood sugar levels) by 12% ().

Berberine is also very effective at improving other health markers.

It lowers triglyceride and blood pressure levels, as well as total and LDL (bad) cholesterol, which may reduce your risk of heart disease ( 1, , , ).

Berberine has also been shown to have antibacterial effects and may protect against heart failure (, , ).

If you want to give berberine a try, you can find it in health stores and online.

However, keep in mind that this substance is very powerful and has a range of biological effects.

Use it with caution and consult your healthcare provider - especially if you're currently taking any other medications.

Summary
Berberine is a powerful supplement. For example, it may help lower blood sugar levels and improve most major risk factors for heart disease.

Turmeric is a popular spice known for giving curry its yellow color.

It has been used as a medicinal herb in India for thousands of years.

Turmeric contains curcumin, a powerful substance that has been studied thoroughly in recent years ().

Curcumin fights inflammation at the molecular level by blocking an inflammatory signalling molecule called NF-kB ( 13, ).

It's so effective that it has been compared to anti-inflammatory drugs in some studies - without any major side effects (, ).

For example, in a study in 45 people with rheumatoid arthritis, 500 mg of curcumin per day was more effective than the anti-inflammatory drug diclofenac ().

Curcumin also has numerous other health benefits. It's a powerful antioxidant, can improve heart health, and may help prevent cancer (, , ).

According to one study, curcumin may also help fight depression. In fact, the results of this study found that curcumin performed as well as the antidepressant drug prozac ().

Nevertheless, curcumin is poorly absorbed, so it's best to get a supplement that also contains piperine/bioperine, which has been shown to enhance its absorption by 2,000% ().

These supplements are widely available in health stores and online.

Summary
Curcumin is the biologically active agent in turmeric. It's a very powerful anti-inflammatory substance that may help fight numerous diseases.

Statin drugs are among the most widely prescribed drugs in the world.

They inhibit the production of cholesterol in your liver, leading to significantly reduced blood cholesterol levels.

Interestingly, an extract of a type of fermented rice called red yeast rice may have similar effects.

It contains small amounts of monacolin K, which is the active ingredient in the statin drug Lovastatin ().

According to a review of 93 studies, red yeast rice lowered total cholesterol by 34 mg/dL on average, LDL (bad) cholesterol by 28 mg/dL, and triglycerides by 35 mg/dL. Plus, it increased HDL (good) cholesterol by 6 mg/dL ().

What's more, in a study in 5,000 people in China who had experienced heart attacks, red yeast rice reduced the risk of subsequent heart attacks by 45% and the risk of dying during the study period by 33% ().

Still, the amount of the active ingredient in supplements can vary up to 100-fold depending on the brand ().

Due to the potency of monacolin K, the Food and Drug Administration (FDA) has ruled that red yeast rice products containing this substance should be considered a drug rather than a supplement ().

Some manufacturers try to evade these regulations by selling red yeast rice supplements that only contain trace amounts of monacolin K.

Therefore, these products may not offer the same benefits as true red yeast rice.

For this reason - and due to potential side effects - you should ask your healthcare provider to help you find a high-quality supplement from a reputable manufacturer.

Summary
Red yeast rice contains a substance that's the active ingredient in the statin drug Lovastatin. It can reduce cholesterol levels and the risk of heart attacks and death in people who already have heart disease.

Garlic is a popular ingredient in cuisines worldwide, but it has also been used as a medicinal plant for thousands of years, including by the Greeks and Romans ().

The main effects of garlic are due to one of its active compounds, allicin, which is highly beneficial for heart health ().

Studies show that garlic can lower total and LDL (bad) cholesterol by 10-15%, on average (, , ).

Even more importantly, aged garlic extract can significantly lower blood pressure, which is a major risk factor for heart attacks, strokes, kidney disease, and early death (, ).

In people with elevated levels, garlic can lower systolic blood pressure (the top number in a reading) by 8.4 mm Hg and diastolic blood pressure (the lower number) by 7.3 mm Hg, on average ().

In one study in 210 people with high blood pressure, garlic tablets were even more effective than the blood-pressure-lowering drug atenolol ().

Garlic also appears to boost immune function and fight the common cold.

In one study, it reduced the number of colds by 63% and the duration of cold symptoms by 70% - from 5 to 1.5 days, on average ().

You can buy garlic supplements in stores and online. Supplements containing aged garlic extract are available as well.

Summary
Garlic has a wide range of biological effects. It can lower blood pressure, improve cholesterol levels, and help fight the common cold.

Supplements, no matter how effective, can never replace a healthy lifestyle with real food, exercise, and good sleep.

That said, the above supplements may aid people who want a natural health boost.

Keep in mind that these supplements are incredibly powerful and should be consumed carefully.

If you have a medical condition or take any medications, consult with your healthcare provider before trying these substances.

# data[].attributes.attachment_link.title
4 Natural Supplements That Are as Powerful as Drugs

# data[].attributes.attachment_link.description
Some supplements can have powerful effects. Here is a list of 4 natural supplements that are just as effective as pharmaceutical drugs.

# data[].attributes.attachment_link.title
Tablets for depression - Do antidepressants help? | DW Documentary

# data[].attributes.headline
How antidepressants affect your sexuality?

# data[].attributes.subject
How antidepressants affect your sexuality?

# data[].attributes.body
What is anxiety?

Anxiety is a constant, uncontrolled feeling of worry that doesn’t stop. When these feelings become strong enough and frequent enough to severely interfere with day to day activities, it’s an anxiety disorder.

Traditional treatments and therapies include psychotherapy—like cognitive behavioral therapy—and medication, such as antidepressants.

Supplements for anxiety:

Ashwagandha - An Ayurvedic herb that works well for anxiety and insomnia, it has been shown to improve sleep and stress resilience. More research on the right amount and length of time ashwagandha must be reviewed.

L-Theanine - A plant-based compound most commonly found in tea leaves. It has some positive studies for its effect on sleep initiation, and conflicting studies on anxiety.

Magnesium - clinical studies suggest that when combined with other vitamins like vitamin B6 or zinc, it may be a promising treatment for easing anxiety in a range of populations, including stressed adults and people with type 2 diabetes.

Vitamin D/B6 - There are a small amount of studies.

CBD - A plant-based bioactive compound found in the cannabis plant. One of the top reasons people say they use CBD is to help treat self-reported anxiety. Evidence of CBD’s effects on anxiety is still very limited.

# data[].attributes.attachment_link.readable_text
Read on for the latest research and expert advice on supplements for anxiety, who may benefit, who may not and a few specific types of supplements that may provide relief for some people.

FEATURED PARTNER OFFER

What Is Anxiety?

According to the American Psychological Association, anxiety is a constant, uncontrolled feeling of worry that doesn't stop. The Centers for Disease Control and Prevention (CDC) estimates approximately 12% of the U.S. adult population has regular feelings of worry, nervousness or anxiety.

Traditional treatments and therapies for anxiety include psychotherapy-like cognitive behavioral therapy-and medication, such as antidepressants. These therapies are well-researched and scientifically proven to be effective for treating anxiety.

Can Supplements Help Anxiety?

Approximately 40% of people with moderate mental distress, which often includes anxiety, say they turn to complementary and alternative medicine approaches, like supplements, for therapeutic relief.

So, can supplements help ease anxiety? The short answer is maybe-and it's dependent on both the cause and severity of the anxiety. However, it's always advisable to consult with your doctor before adding any type of supplement to your diet, or exploring alternative treatments.

Supplements for Anxiety: The Importance of a Personalized Approach

"Anxiety can present very differently in two people with the same diagnosis," explains Ripal Shah, M.D., clinical assistant professor at the Stanford University School of Medicine. "One may have primarily physical symptoms (palpitations) when stressed or anxious, and another may feel physically calm but internally restless (racing thoughts)."

Trying a supplement that affects the part of the nervous system that controls our "fight or flight" stress response may help a person with physical symptoms ease their anxiety. But, this same supplement might not be effective for someone with emotional symptoms.

So, it's very important to take a personalized approach when navigating anxiety supplements.

What also remains very clear about the role supplements may play as a therapy for anxiety is they're not a standalone, "cure-all" solution-and they're typically only one part of additional lifestyle approaches aimed at anxiety management

"If we are looking for a supplement to alter our brain activity but haven't worked on our exercise pattern, developed a daily mind-body practice, found a workable whole foods dietary approach, etc., supplements are going to have a less-than-hoped-for impact," says Brent Bauer, M.D., director of the Mayo Clinic Complementary and Integrative Medicine Program.

"I always tell my patients, 'supplements are supplementary.' If there is a [vitamin] deficiency, we may consider supplements, but there can be risks to taking unnecessary and/or multiple supplements," adds Michelle Loy, M.D., an integrative medicine physician with the Integrative Health and Wellbeing Center at Weill Cornell Medicine.

With all that being said, dietary supplements for anxiety may be beneficial for some people, especially for individuals who:

Have a known nutrient deficiency

Have mild and only occasional symptoms

Are resistant to taking medication

Haven't responded to other traditional therapy

FEATURED PARTNER OFFER

Who Should Avoid Supplements for Anxiety?

Experts stress the importance of always reviewing and discussing any new supplement aimed at easing anxiety with a licensed and knowledgeable medical practitioner before starting them.

"Anything powerful enough to have a beneficial effect must also have the power to have a negative effect as well," explains Dr. Bauer.

There are potential side effects and even dangers to taking supplements for anxiety for the following people:

People taking certain medications that might interfere or interact with certain supplements.

People with other mental health conditions or medical conditions, where supplementation may make existing stress and anxiety-induced symptoms worse or cause new symptoms.

People with severe anxiety who need access to immediate treatment.

People who are pregnant or breastfeeding (unless they talk to a doctor first).

"In my personal practice, I encourage my patients to work with a variety of mind-body practices (in addition to nutrition, exercise, etc.) for at least three months before we consider supplements," notes Dr. Bauer.

Top Supplements That May Help Ease Anxiety

There are many supplements that claim to help with anxiety. The process of finding the right one may be a bit of trial and error, but should always be done with a doctor's help.

"If my patient is considering a supplement, we review the known risks and benefits and then use a database to scan for any known interactions with their current medications," says Dr. Bauer.

A few common supplements that may help ease anxiety include the following.

Ashwagandha

An Ayurvedic herb that may work especially well for those with anxiety and insomnia, ashwagandha has been shown to improve sleep and stress resilience. It's also an herb Dr. Loy recommends.

Recent reviews on the safety and efficacy of ashwagandha for anxiety suggest that while effects are generally positive, study sizes are small. More research on the right amount and length of time ashwagandha must be taken as a replacement for or adjunct to traditional therapies are needed.

L-Theanine

L-theanine is a plant-based compound most commonly found in tea leaves. "L-theanine has some positive studies for its effect on sleep initiation, and conflicting studies on anxiety," says Dr. Shah.

A 2022 review of studies in Pharmacological Research found that compared to groups not receiving L-theanine, the groups taking L-theanine did not see a significant benefit in terms of treatment for anxiety. However, a 2015 study in Journal of the American College of Nutrition does point to L-theanine's effectiveness in helping to improve sleep quality-so individuals dealing with sleep issues may find this supplement helpful.

Magnesium

Recent clinical studies suggest that magnesium supplementation, when combined with other vitamins like vitamin B6 or zinc, may be a promising treatment for easing anxiety in a range of populations, including stressed adults and people with type 2 diabetes and heart disease. Additionally, most Americans are deficient in this mineral and often don't get enough from their diet.

When it comes to concrete recommendations for magnesium for anxiety across the board, however, more studies need to be done. "Currently, there is limited and inconclusive evidence on magnesium and its role in anxiety," explains Monique Richard, an integrative dietitian and national media spokesperson for the Academy of Nutrition and Dietetics.

FEATURED PARTNER OFFER

Vitamin D

"While there are small studies that hint at the possible benefit of vitamin D in anxiety or depression, the research is still unclear as to whether vitamin D supplementation can relieve symptoms," says Dr. Loy.

For instance, researchers still need to explore how vitamin D supplementation impacts people of different ages and types of anxiety. Scientists are also evaluating if taking vitamin D with other nutrients, such as vitamin B6 or omega-3 fatty acids, has any efficacy.

Vitamin B6

A 2022 randomized controlled trial in Human Psychopharmacology randomly assigned 478 young adults who were predominantly female to take lactose tablets, vitamin B6 tablets or vitamin B12 tablets for one month. The group supplementing with a high dose vitamin B6 self-reported a reduced level of anxiety.

CBD

Cannabidiol (CBD) is a plant-based bioactive compound found in the cannabis plant. One of the top reasons people say they use CBD is to help treat self-reported anxiety.

However, scientific evidence regarding CBD's effects on anxiety is still very limited.

Interestingly, a small 2021 study in Psychopharmacology looked at what might be responsible for the self-reported reputation CBD seems to have when it comes to improving anxiety despite such limited and conflicting scientific support.

Researchers randomly assigned 43 otherwise healthy adults to take CBD-free hemp seed oil in two possible sessions. In the first, they were told it contained CBD (expectancy condition) and the second they were told it did not.

As with many of the other supplements involved in this article, these two conflicting studies show the need for more clinical trials around CBD and anxiety.

Unlock Serenity And Relaxation

Other Supplements for Anxiety

There are many other supplements marketed towards easing anxiety, including:

Chamomile

Lavender

Lemon balm

Kava kava

Passionflower

Omega 3 fatty acids

That said, "simply seeing it advertised or available on a store shelf does not mean it may be an appropriate option for your individual needs," says Richard.

To navigate all of the conflicting and confusing messaging around which supplements are safe and effective for anxiety, it's a good idea to work with a medical provider who has expertise in determining which supplements may be right for you, such as an integrative or functional medicine physician or registered dietitian nutritionist (RDN).

What to Look for When Choosing a Supplement for Anxiety

Third-Party Testing

"Supplements are not regulated by the FDA, [so] it is in the consumer's best interest to do their due diligence about any item they are ingesting," cautions Richard.

Making sure there has been third-party verification or testing of the supplement (i.e., not from the supplement manufacturer), is one way to gather information on the accuracy of the ingredients list and potency of the contents, adds Dr. Shah.

Look for one of the following third-party seals or verifications on the bottle or within materials accompanying a supplement:

NSF International

US Pharmacopeia (USP)

Consumer Labs

Another factor is how transparent the supplement brand is. "I recommend choosing brands that are transparent about the Certificates of Analysis (CoA) for supplement purity and those that show where their herbs are sourced (QR codes in some cases)," says Dr. Loy. It's also a good idea to look for transparency around the dosing of the active ingredient and to see if the brand prioritizes clinically validated ingredients overall.

There are many supplements that claim to help with anxiety, all with varying levels of scientific support for their safety and efficacy. As research continues, it may soon become more clear which supplements are actually worth your time, but for now, it's always a good idea to speak with your doctor first before starting any new supplementation routine.

Additionally, supplements are only one tool in the toolbox for easing anxiety. Lifestyle changes, along with traditional treatments, are still widely recommended by physicians and experts. And supplements cannot-and should not-replace the role of anxiety medication for some individuals.

Lastly, if you're interested in trying supplements to ease anxiety, always keep in mind that most supplements are unregulated and can have occasional side effects.

# data[].attributes.attachment_link.title
Top Natural Supplements For Anxiety: Do They Work?

# data[].attributes.attachment_link.description
Top Natural Supplements For Anxiety: Do They Work?

# data[].attributes.attachment_link.description
Learn about all the different kinds of diabetes and the basics of this condition.

# data[].attributes.attachment_link.description
WHO fact sheet on HIV and AIDS with key facts and information on signs and symptoms, transmission, risk factors, testing and counselling, prevention, treatment and WHO response.

# data[].attributes.attachment_link.readable_text
Air pollution is the single largest environmental health risk in Europe and a major cause of premature death and disease. Latest estimates by the European Environment Agency (EEA) show that fine particulate matter (PM 2.5) continues to cause the most substantial health impacts.

Most Europeans live in areas, especially cities, where air pollution can reach high levels. Both short- and long-term exposure to air pollution can lead to a wide range of diseases, including stroke, chronic obstructive pulmonary disease, trachea, bronchus and lung cancers, aggravated asthma and lower respiratory infections. The World Health Organization (WHO) provides evidence of links between exposure to air pollution and type 2 diabetes, obesity, systemic inflammation, Alzheimer's disease and dementia. The International Agency for Research on Cancer has classified air pollution, in particular PM 2.5, as a leading cause of cancer. A recent global review found that chronic exposure can affect every organ in the body, complicating and exacerbating existing health conditions.

Children and adolescents are particularly vulnerable because their bodies, organs and immune systems are still developing. Air pollution damages health during childhood and increases the risk of diseases later in life, yet children can do little to protect themselves or influence air quality policies.
Note: Particulate matter with a diameter of 2.5 µm or less (PM2.5), particulate matter with a diameter of 10 µm or less (PM₁₀), ozone (O₃), nitrogen dioxide (NO₂), benzo[a]pyrene (BaP) and sulphur dioxide (SO₂).
Fine particulate matter (PM2.5) is the air pollutant driving the most significant health problems and premature mortality. In 2021, 97% of the urban population was exposed to concentrations of fine particulate matter above the health-based guideline level set by the World Health Organization.

The EEA estimates that, in 2020, approximately 238,000 premature deaths were attributable to PM 2.5 in the 27 EU Member States. In 2020, premature deaths attributed to exposure to fine particulate matter fell by 45% in the EU-27, compared to 2005.

Residential, commercial and institutional energy consumption was the principal source of particulate matter in 2020. The manufacturing and extractive industry was also a significant source, while agriculture was an equally important source of PM ₁₀. Between 2005 and 2020, emissions of particulate matter, PM ₁₀ and PM 2.5, fell by 30% and 32%, respectively.

In 2021, the World Health Organization (WHO) published new air quality guidelines following a systematic review of the latest scientific evidence demonstrating how air pollution damages human health. The European Union (EU) has also set standards for key air pollutants in the ambient air quality directives. In the European Green Deal, the European Commission committed to further improving air quality and to aligning EU air quality standards more closely with the WHO recommendations. This commitment was echoed in the zero pollution action plan, which set a vision for 2050 to reduce air, water and soil pollution to levels no longer considered harmful to health and natural ecosystems. In addition, the zero pollution action plan introduced targets for 2030, two of which focus on air and aim to:

reduce the health impacts of air pollution (premature deaths) by more than 55%, compared to 2005;

reduce the share of EU ecosystems where air pollution threatens biodiversity by 25%, compared to 2005.

Stricter air quality standards would also contribute to the objectives of Europe's Beating Cancer Plan. Air pollution is a known cause of cancer in Europe; in particular, lung cancer ( EEA, 2022).

In terms of the past trend, from 2005 to 2020, premature deaths attributed to PM 2.5 exposure in the EU-27 fell by 33% to reach 238,000. Should air quality continue to improve, and the number of premature deaths per year continue to fall at a comparable rate in the future, then the zero pollution target would be achieved by 2032, as shown in the figure below.

In October 2022, the European Commission published a proposal for a revision of the Ambient Air Quality Directive. Key measures are listed below.

Stricter thresholds for pollution, more closely aligned with new limits set by the World Health Organization.

Enhancing the right to clean air, improved access to justice.

Current law does not include provisions for citizens to claim compensation for health damage due to air pollution. The new rules will bring more effective penalties and compensation possibilities for violating air quality rules.

Strengthened rules for air quality monitoring to support preventive action and targeted measures.

Requirements to improve air quality modelling, especially if and where air quality is poor.

Better public information.

The above measures are aligned with other legislative proposals, such as the revision of the Industrial Emissions Directive and recent proposals on the Euro 7 emission standards for road vehicles, which will support the achievement of stricter air quality standards.

Air pollution affects people in different ways. Older people, children and those with pre-existing health conditions are more sensitive to the health impacts of air pollution. In addition, the most deprived people in society often have poorer health and less access to high-quality medical care, increasing their vulnerability.

There is strong evidence linking lower socio-economic status to increased exposure to air pollution. In large parts of Europe, poorer people are more likely to live next to busy roads or industrial areas and thus, face higher levels of exposure to air pollution. At the same time, exposure patterns vary across European cities. In some cities, wealthier people live in central, polluted areas, while in other European cities central areas are inhabited by poorer communities.

In Europe, regions characterised by lower GDP per capita are found to have higher levels of PM 2.5 and tend to occur in Eastern and South-eastern Europe. This pattern is largely driven by the combustion of low-quality solid fuels (e.g. coal and wood) in low-efficiency ovens for domestic heating in those areas. The higher population exposure to PM 2.5 in particular regions, translates into higher numbers of premature deaths attributed to air pollution.

Mapping mortality attributed to PM2.5 against regional wealth in Europe

Besides premature death, air pollution also causes morbidity. People live with diseases related to exposure to air pollution; this is a burden in terms of personal suffering as well as significant costs on the healthcare sector. In 2019, exposure to PM 2.5 led to 175,702 years lived with disability (YLDs) due to chronic obstructive pulmonary disease in 30 European countries. At the same time, exposure to NO2 led to 175,070 YLDs due to diabetes mellitus (also known as Type 2 diabetes) in 31 European countries. That same year, 12,253 people across 23 European countries were admitted to the hospital with lower respiratory infections resulting from acute exposure to ozone.

The interactive map viewer shows the spatial distribution of population-weighted concentrations of PM 2.5 (as an indication of population exposure) across Europe and the associated mortality. The viewer also allows to display data against GDP per capita as a proxy for the average socio-economic characteristics of the population in each region. The data is presented for NUTS3 regions (between 150,000 and 800,000 inhabitants).
Interactive map: Associations between exposure to PM2.5, mortality and GDP per capita GDP per capita - Eurostat; Premature deaths, years of life lost and population-weighted concentrations are based on an EEA analysis of interpolated annual statistics of reported monitoring data from 2018 (see Map 9.1 in EEA, 2020) and the Geostat 2011 population grid data set.

# data[].attributes.attachment_link.description
Air pollution is the single largest environmental health risk in Europe and a major cause of premature death and disease. Latest estimates by the European Environment Agency (EEA) show that fine particulate matter (PM 2.5 ) continues to cause the most substantial health impacts.

# data[].attributes.attachment_link.readable_text
Research Center for Economy of Upper Reaches of the Yangtse River/School of Economics, Chongqing Technology and Business University, Chongqing, China

School of Economics and Management, Huzhou University, Huzhou, China

Background: More than 80% of sewage generated by human activities is discharged into rivers and oceans without any treatment, which results in environmental pollution and more than 50 diseases. 80% of diseases and 50% of child deaths worldwide are related to poor water quality.

Methods: This paper selected 85 relevant papers finally based on the keywords of water pollution, water quality, health, cancer, and so on.

Results: The impact of water pollution on human health is significant, although there may be regional, age, gender, and other differences in degree. The most common disease caused by water pollution is diarrhea, which is mainly transmitted by enteroviruses in the aquatic environment.

Discussion: Governments should strengthen water intervention management and carry out intervention measures to improve water quality and reduce water pollution's impact on human health.

Introduction

Water is an essential resource for human survival. According to the 2021 World Water Development Report released by UNESCO, the global use of freshwater has increased six-fold in the past 100 years and has been growing by about 1% per year since the 1980s. With the increase of water consumption, water quality is facing severe challenges. Industrialization, agricultural production, and urban life have resulted in the degradation and pollution of the environment, adversely affecting the water bodies (rivers and oceans) necessary for life, ultimately affecting human health and sustainable social development ( Xu et al., 2022a). Globally, an estimated 80% of industrial and municipal wastewater is discharged into the environment without any prior treatment, with adverse effects on human health and ecosystems. This proportion is higher in the least developed countries, where sanitation and wastewater treatment facilities are severely lacking.

Sources of Water Pollution

Water pollution are mainly concentrated in industrialization, agricultural activities, natural factors, and insufficient water supply and sewage treatment facilities. First, industry is the main cause of water pollution, these industries include distillery industry, tannery industry, pulp and paper industry, textile industry, food industry, iron and steel industry, nuclear industry and so on. Various toxic chemicals, organic and inorganic substances, toxic solvents and volatile organic chemicals may be released in industrial production. If these wastes are released into aquatic ecosystems without adequate treatment, they will cause water pollution ( Chowdhary et al., 2020). Arsenic, cadmium, and chromium are vital pollutants discharged in wastewater, and the industrial sector is a significant contributor to harmful pollutants ( Chen et al., 2019). With the acceleration of urbanization, wastewater from industrial production has gradually increased. ( Wu et al., 2020). In addition, water pollution caused by industrialization is also greatly affected by foreign direct investment. Industrial water pollution in less developed countries is positively correlated with foreign direct investment ( Jorgenson, 2009). Second, water pollution is closely related to agriculture. Pesticides, nitrogen fertilizers and organic farm wastes from agriculture are significant causes of water pollution (RCEP, 1979). Agricultural activities will contaminate the water with nitrates, phosphorus, pesticides, soil sediments, salts and pathogens ( Parris, 2011). Furthermore, agriculture has severely damaged all freshwater systems in their pristine state ( Moss, 2008). Untreated or partially treated wastewater is widely used for irrigation in water-scarce regions of developing countries, including China and India, and the presence of pollutants in sewage poses risks to the environment and health. Taking China as an example, the imbalance in the quantity and quality of surface water resources has led to the long-term use of wastewater irrigation in some areas in developing countries to meet the water demand of agricultural production, resulting in serious agricultural land and food pollution, pesticide residues and heavy metal pollution threatening food safety and Human Health ( Lu et al., 2015). Pesticides have an adverse impact on health through drinking water. Comparing pesticide use with health life Expectancy Longitudinal Survey data, it was found that a 10% increase in pesticide use resulted in a 1% increase in the medical disability index over 65 years of age ( Lai, 2017). The case of the Musi River in India shows a higher incidence of morbidity in wastewater-irrigated villages than normal-water households. Third, water pollution is related to natural factors. Taking Child Loess Plateau as an example, the concentration of trace elements in water quality is higher than the average world level, and trace elements come from natural weathering and manufacture causes. Poor river water quality is associated with high sodium and salinity hazards ( Xiao et al., 2019). The most typical water pollution in the middle part of the loess Plateau is hexavalent chromium pollution, which is caused by the natural environment and human activities. Loess and mudstone are the main sources, and groundwater with high concentrations of hexavalent chromium is also an important factor in surface water pollution (He et al., 2020). Finally, water supply and sewage treatment facilities are also important factors affecting drinking water quality, especially in developing countries. In parallel with China rapid economic growth, industrialization and urbanization, underinvestment in basic water supply and treatment facilities has led to water pollution, increased incidence of infectious and parasitic diseases, and increased exposure to industrial chemicals, heavy metals and algal toxins ( Wu et al., 1999). An econometric model predicts the impact of water purification equipment on water quality and therefore human health. When the proportion of household water treated with water purification equipment is reduced from 100% to 90%, the expected health benefits are reduced by up to 96%.. When the risk of pretreatment water quality is high, the decline is even more significant ( Brown and Clasen, 2012).

To sum up, water pollution results from both human and natural factors. Various human activities will directly affect water quality, including urbanization, population growth, industrial production, climate change, and other factors ( Halder and Islam, 2015) and religious activities ( Dwivedi et al., 2018). Improper disposal of solid waste, sand, and gravel is also one reason for decreasing water quality ( Ustaoğlua et al., 2020).

Impact of Water Pollution on Human Health

Unsafe water has severe implications for human health. According to UNESCO 2021 World Water Development Report, about 829,000 people die each year from diarrhea caused by unsafe drinking water, sanitation, and hand hygiene, including nearly 300,000 children under the age of five, representing 5.3 percent of all deaths in this age group. Data from Palestine suggest that people who drink municipal water directly are more likely to suffer from diseases such as diarrhea than those who use desalinated and household-filtered drinking water ( Yassin et al., 2006). In a comparative study of tap water, purified water, and bottled water, tap water was an essential source of gastrointestinal disease ( Payment et al., 1997). Lack of water and sanitation services also increases the incidence of diseases such as cholera, trachoma, schistosomiasis, and helminthiasis. Data from studies in developing countries show a clear relationship between cholera and contaminated water, and household water treatment and storage can reduce cholera ( Gundry et al., 2004). In addition to disease, unsafe drinking water, and poor environmental hygiene can lead to gastrointestinal illness, inhibiting nutrient absorption and malnutrition. These effects are especially pronounced for children.

Purpose of This Paper

More than two million people worldwide die each year from diarrhoeal diseases, with poor sanitation and unsafe drinking water being the leading cause of nearly 90% of deaths and affecting children the most (United Nations, 2016). More than 50 kinds of diseases are caused by poor drinking water quality, and 80% of diseases and 50% of child deaths are related to poor drinking water quality in the world. However, water pollution causes diarrhea, skin diseases, malnutrition, and even cancer and other diseases related to water pollution. Therefore, it is necessary to study the impact of water pollution on human health, especially disease heterogeneity, and clarify the importance of clean drinking water, which has important theoretical and practical significance for realizing sustainable development goals. Unfortunately, although many kinds of literature focus on water pollution and a particular disease, there is still a lack of research results that systematically analyze the impact of water pollution on human health and the heterogeneity of diseases. Based on the above background and discussion, this paper focuses on the effect of water pollution on human health and its disease heterogeneity.

Materials and Methods

Search Process

This article uses keywords such as "water," "water pollution," "water quality," "health," "diarrhea," "skin disease," "cancer" and "children" to search Web of Science and Google Scholar include SCI and SSCI indexed papers, research reports, and works from 1990 to 2021.

Inclusion-Exclusion Criteria and Data Extraction Process

The existing literature shows that water pollution and human health are important research topics in health economics, and scholars have conducted in-depth research. As of 30 December 2021, 104 related literatures were searched, including research papers, reviews and conference papers. Then, according to the content relevancy, 19 papers were eliminated, and 85 papers remained. The purpose of this review is to summarize the impact of water pollution on human health and its disease heterogeneity and to explore how to improve human health by improving water pollution control measures.

Information extracted from all included papers included: author, publication date, sample country, study methodology, study purpose, and key findings. All analysis results will be analyzed according to the process in Figure 1.

FIGURE 1. Data extraction process (PRISMA).

The relevant information of the paper is exported to the Excel database through Endnote, and the duplicates are deleted. The results were initially extracted by one researcher and then cross-checked by another researcher to ensure that all data had been filtered and reviewed. If two researchers have different opinions, the two researchers will review together until a final agreement is reached.

Quality Assessment of the Literature

The JBI Critical Appraisal Checklist was used to evaluate the quality of each paper. The JBI (Joanna Briggs Institute) key assessment tool was developed by the JBI Scientific Committee after extensive peer review and is designed for system review. All features of the study that meet the following eight criteria are included in the final summary:1) clear purpose; 2) Complete information of sample variables; 3) Data basis; 4) the validity of data sorting; 5) ethical norms; (6); 7) Effective results; 8) Apply appropriate quantitative methods and state the results clearly. Method quality is evaluated by the Yes/No questions listed in the JBI Key Assessment List. Each analysis paper received 6 out of 8.

Results

The quality of drinking water is an essential factor affecting human health. Poor drinking water quality has led to the occurrence of water-borne diseases. According to the World Health Organization (WHO) survey, 80% of the world's diseases and 50% of the world's child deaths are related to poor drinking water quality, and there are more than 50 diseases caused by poor drinking water quality. The quality of drinking water in developing countries is worrying. The negative health effects of water pollution remain the leading cause of morbidity and mortality in developing countries. Different from the existing literature review, this paper mainly studies the impact of water pollution on human health according to the heterogeneity of diseases. We focuses on diarrhea, skin diseases, cancer, child health, etc., and sorts out the main effects of water pollution on human health ( Table 1).

TABLE 1. Major studies on the relationship between water pollution and health.

Water Pollution and Diarrhea

Diarrhea is a common symptom of gastrointestinal diseases and the most common disease caused by water pollution. Diarrhea is a leading cause of illness and death in young children in low-income countries. Diarrhoeal diseases account for 21% of annual deaths among children under 5 years of age in developing countries ( Waddington et al., 2009). Many infectious agents associated with diarrhea are directly related to contaminated water ( Ahmed and Ismail, 2018). Parasitic worms present in non-purifying drinking water when is consumed by human beings causes diseases ( Ansari and Akhmatov., 2020) . It was found that treated water from water treatment facilities was associated with a lower risk of diarrhea than untreated water for all ages ( Clasen et al., 2015). For example, in the southern region of Brazil, a study found that factors significantly associated with an increased risk of mortality from diarrhoea included lack of plumbed water, lack of flush toilets, poor housing conditions, and overcrowded households. Households without access to piped water had a 4.8 times higher risk of infant death from diarrhea than households with access to piped water ( Victora et al., 1988)

Enteroviruses exist in the aquatic environment. More than 100 pathogenic viruses are excreted in human and animal excreta and spread in the environment through groundwater, estuarine water, seawater, rivers, sewage treatment plants, insufficiently treated water, drinking water, and private wells ( Fong and Lipp., 2005). A study in Pakistan showed that coliform contamination was found in some water sources. Improper disposal of sewage and solid waste, excessive use of pesticides and fertilizers, and deteriorating pipeline networks are the main causes of drinking water pollution. The main source of water-borne diseases such as gastroenteritis, dysentery, diarrhea, and viral hepatitis in this area is the water pollution of coliform bacteria ( Khan et al., 2013). Therefore, the most important role of water and sanitation health interventions is to hinder the transmission of diarrheal pathogens from the environment to humans ( Waddington et al., 2009).

Meta-analyses are the most commonly used method for water quality and diarrhea studies. It was found that improving water supply and sanitation reduced the overall incidence of diarrhea by 26%. Among Malaysian infants, having clean water and sanitation was associated with an 82% reduction in infant mortality, especially among infants who were not breastfed ( Esrey et al., 1991). All water quality and sanitation interventions significantly reduced the risk of diarrhoeal disease, and water quality interventions were found to be more effective than previously thought. Multiple interventions (including water, sanitation, and sanitation measures) were not more effective than single-focus interventions ( Fewtrell and Colford., 2005). Water quality interventions reduced the risk of diarrhoea in children and reduced the risk of E. coli contamination of stored water ( Arnold and Colford., 2007). Interventions to improve water quality are generally effective in preventing diarrhoea in children of all ages and under 5. However, some trials showed significant heterogeneity, which may be due to the research methods and their conditions ( Clasen et al., 2007).

Water Pollution and Skin Diseases

Contrary to common sense that swimming is good for health, studies as early as the 1950s found that the overall disease incidence in the swimming group was significantly higher than that in the non-swimming group. The survey shows that the incidence of the disease in people under the age of 10 is about 100% higher than that of people over 10 years old. Skin diseases account for a certain proportion ( Stevenson, 1953). A prospective epidemiological study of beach water pollution was conducted in Hong Kong in the summer of 1986-1987. The study found that swimmers on Hong Kong's coastal beaches were more likely than non-swimmers to complain of systemic ailments such as skin and eyes. And swimming in more polluted beach waters has a much higher risk of contracting skin diseases and other diseases. Swimming-related disease symptom rates correlated with beach cleanliness ( Cheung et al., 1990).

A study of arsenic-affected villages in the southern Sindh province of Pakistan emphasized that skin diseases were caused by excessive water quality. By studying the relationship between excessive arsenic in drinking water caused by water pollution and skin diseases (mainly melanosis and keratosis), it was found that compared with people who consumed urban low-arsenic drinking water, the hair of people who consumed high-arsenic drinking water arsenic concentration increased significantly. The level of arsenic in drinking water directly affects the health of local residents, and skin disease is the most common clinical complication of arsenic poisoning. There is a correlation between arsenic concentrations in biological samples (hair and blood) from patients with skin diseases and intake of arsenic-contaminated drinking water ( Kazi et al., 2009). Another Bangladesh study showed that many people suffer from scabies due to river pollution ( Hanif et al., 2020). Not only that, but water pollution from industry can also cause skin cancer ( Arif et al., 2020).

Studies using meta-analysis have shown that exposure to polluted Marine recreational waters can have adverse consequences, including frequent skin discomfort (such as rash or itching). Skin diseases in swimmers may be caused by a variety of pathogenic microorganisms ( Yau et al., 2009). People (swimmers and non-swimmers) exposed to waters above threshold levels of bacteria had a higher relative risk of developing skin disease, and levels of bacteria in seawater were highly correlated with skin symptoms.

Studies have also suggested that swimmers are 3.5 times more likely to report skin diseases than non-swimmers. This difference may be a "risk perception bias" at work on swimmers, who are generally aware that such exposure may lead to health effects and are more likely to detect and report skin disorders. It is also possible that swimmers exaggerated their symptoms, reporting conditions that others would not classify as true skin disorders ( Fleisher and Kay. 2006).

Water Pollution and Cancer

According to WHO statistics, the number of cancer patients diagnosed in 2020 reached 19.3 million, while the number of deaths from cancer increased to 10 million. Currently, one-fifth of all global fevers will develop cancer during their lifetime. The types and amounts of carcinogens present in drinking water will vary depending on where they enter: contamination of the water source, water treatment processes, or when the water is delivered to users ( Morris, 1995).

From the perspective of water sources, arsenic, nitrate, chromium, etc. are highly associated with cancer. Ingestion of arsenic from drinking water can cause skin cancer and kidney and bladder cancer ( Marmot et al., 2007). The risk of cancer in the population from arsenic in the United States water supply may be comparable to the risk from tobacco smoke and radon in the home environment. However, individual susceptibility to the carcinogenic effects of arsenic varies ( Smith et al., 1992). A high association of arsenic in drinking water with lung cancer was demonstrated in a northern Chilean controlled study involving patients diagnosed with lung cancer and a frequency-matched hospital between 1994 and 1996. Studies have also shown a synergistic effect of smoking and arsenic intake in drinking water in causing lung cancer ( Ferreccio et al., 2000). Exposure to high arsenic levels in drinking water was also associated with the development of liver cancer, but this effect was not significant at exposure levels below 0.64 mg/L ( Lin et al., 2013).

Nitrates are a broader contaminant that is more closely associated with human cancers, especially colorectal cancer. A study in East Azerbaijan confirmed a significant association between colorectal cancer and nitrate in men, but not in women (Maleki et al., 2021). The carcinogenic risk of nitrates is concentration-dependent. The risk increases significantly when drinking water levels exceed 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Drinking water with nitrate concentrations lower than current drinking water standards also increases the risk of colorectal cancer ( Schullehner et al., 2018).

Drinking water with high chromium content will bring high carcinogenicity caused by hexavalent chromium to residents. Drinking water intake of hexavalent chromium experiments showed that hexavalent chromium has the potential to cause human respiratory cancer. ( Zhitkovich, 2011). A case from Changhua County, Taiwan also showed that high levels of chromium pollution were associated with gastric cancer incidence ( Tseng et al., 2018).

There is a correlation between trihalomethane (THM) levels in drinking water and cancer mortality. Bladder and brain cancers in both men and women and non-Hodgkin's lymphoma and kidney cancer in men were positively correlated with THM levels, and bladder cancer mortality had the strongest and most consistent association with THM exposure index ( Cantor et al., 1978).

From the perspective of water treatment process, carcinogens may be introduced during chlorine treatment, and drinking water is associated with all cancers, urinary cancers and gastrointestinal cancers ( Page et al., 1976). Chlorinated byproducts from the use of chlorine in water treatment are associated with an increased risk of bladder and rectal cancer, with perhaps 5,000 cases of bladder and 8,000 cases of rectal cancer occurring each year in the United States (Morris, 1995).

The impact of drinking water pollutants on cancer is complex. Epidemiological studies have shown that drinking water contaminants, such as chlorinated by-products, nitrates, arsenic, and radionuclides, are associated with cancer in humans ( Cantor, 1997). Pb, U, F- and no3- are the main groundwater pollutants and one of the potential causes of cancer ( Kaur et al., 2021). In addition, many other water pollutants are also considered carcinogenic, including herbicides and pesticides, and fertilizers that contain and release nitrates ( Marmot et al., 2007). A case from Hebei, China showed that the contamination of nitrogen compounds in well water was closely related to the use of nitrogen fertilizers in agriculture, and the levels of three nitrogen compounds in well water were significantly positively correlated with esophageal cancer mortality ( Zhang et al., 2003).

In addition, due to the time-lag effect, the impact of watershed water pollution on cancer is spatially heterogeneous. The mortality rate of esophageal cancer caused by water pollution is significantly higher downstream than in other regions due to the impact of historical water pollution ( Xu et al., 2019). A study based on changes in water quality in the watershed showed that a grade 6 deterioration in water quality resulted in a 9.3% increase in deaths from digestive cancer. ( Ebenstein, 2012).

Water Pollution and Child Health

Diarrhea is a common disease in children. Diarrhoeal diseases (including cholera) kill 1.8 million people each year, 90 per cent of them children under the age of five, mostly in developing countries. 88% of diarrhoeal diseases are caused by inadequate water supply, sanitation and hygiene (Team, 2004). A large proportion of these are caused by exposure to microbially infected water and food, and diarrhea in infants and young children can lead to malnutrition and reduced immune resistance, thereby increasing the likelihood of prolonged and recurrent diarrhea ( Marino, 2007). Pollution exposure experienced by children during critical periods of development is associated with height loss in adulthood ( Zaveri et al., 2020). Diseases directly related to water and sanitation, combined with malnutrition, also lead to other causes of death, such as measles and pneumonia. Child malnutrition and stunting due to inadequate water and sanitation will continue to affect more than one-third of children in the world ( Bartlett, 2003). A study from rural India showed that children living in households with tap water had significantly lower disease prevalence and duration ( Jalan and Ravallion, 2003).

In conclusion, water pollution is a significant cause of childhood diseases. Air, water, and soil pollution together killed 940,000 children worldwide in 2016, two-thirds of whom were under the age of 5, and the vast majority occurred in low- and middle-income countries ( Landrigan et al., 2018). The intensity of industrial organic water pollution is positively correlated with infant mortality and child mortality in less developed countries, and industrial water pollution is an important cause of infant and child mortality in less developed countries ( Jorgenson, 2009). In addition, arsenic in drinking water is a potential carcinogenic risk in children (García-Rico et al., 2018). Nitrate contamination in drinking water may cause goiter in children ( Vladeva et al.., 2000).

Discussions

This paper reviews the environmental science, health, and medical literature, with a particular focus on epidemiological studies linking water quality, water pollution, and human disease, as well as studies on water-related disease morbidity and mortality. At the same time, special attention is paid to publications from the United Nations and the World Health Organization on water and sanitation health research. The purpose of this paper is to clarify the relationship between water pollution and human health, including: The relationship between water pollution and diarrhea, the mechanism of action, and the research situation of meta-analysis; The relationship between water pollution and skin diseases, pathogenic factors, and meta-analysis research; The relationship between water pollution and cancer, carcinogenic factors, and types of cancer; The relationship between water pollution and Child health, and the major childhood diseases caused.

A study of more than 100 literatures found that although factors such as country, region, age, and gender may have different influences, in general, water pollution has a huge impact on human health. Water pollution is the cause of many human diseases, mainly diarrhoea, skin diseases, cancer and various childhood diseases. The impact of water pollution on different diseases is mainly reflected in the following aspects. Firstly, diarrhea is the most easily caused disease by water pollution, mainly transmitted by enterovirus existing in the aquatic environment. The transmission environment of enterovirus depends on includes groundwater, river, seawater, sewage, drinking water, etc. Therefore, it is necessary to prevent the transmission of enterovirus from the environment to people through drinking water intervention. Secondly, exposure to or use of heavily polluted water is associated with a risk of skin diseases. Excessive bacteria in seawater and heavy metals in drinking water are the main pathogenic factors of skin diseases. Thirdly, water pollution can pose health risks to humans through any of the three links: the source of water, the treatment of water, and the delivery of water. Arsenic, nitrate, chromium, and trihalomethane are major carcinogens in water sources. Carcinogens may be introduced during chlorine treatment from water treatment. The effects of drinking water pollution on cancer are complex, including chlorinated by-products, heavy metals, radionuclides, herbicides and pesticides left in water, etc., Finally, water pollution is an important cause of children's diseases. Contact with microbiologically infected water can cause diarrhoeal disease in children. Malnutrition and weakened immunity from diarrhoeal diseases can lead to other diseases.

This study systematically analyzed the impact of water pollution on human health and the heterogeneity of diseases from the perspective of different diseases, focusing on a detailed review of the relationship, mechanism and influencing factors of water pollution and diseases. From the point of view of limitations, this paper mainly focuses on the research of environmental science and environmental management, and the research on pathology is less involved. Based on this, future research can strengthen research at medical and pathological levels.

In response to the above research conclusions, countries, especially developing countries, need to adopt corresponding water management policies to reduce the harm caused by water pollution to human health. Firstly, there is a focus on water quality at the point of use, with interventions to improve water quality, including chlorination and safe storage ( Gundry et al., 2004), and provision of treated and clean water ( Khan et al., 2013). Secondly, in order to reduce the impact of water pollution on skin diseases, countries should conduct epidemiological studies on their own in order to formulate health-friendly bathing water quality standards suitable for their specific conditions ( Cheung et al., 1990). Thirdly, in order to reduce the cancer caused by water pollution, the whole-process supervision of water quality should be strengthened, that is, the purity of water sources, the scientific nature of water treatment and the effectiveness of drinking water monitoring. Fourthly, each society should prevent and control source pollution from production, consumption, and transportation ( Landrigan et al., 2018). Fifthly, health education is widely carried out. Introduce environmental education, educate residents on sanitary water through newspapers, magazines, television, Internet and other media, and enhance public health awareness. Train farmers to avoid overuse of agricultural chemicals that contaminate drinking water.

Author Contributions

Conceptualization, XX|; methodology, LL; data curation, HY; writing and editing, LL; project administration, XX|.

Funding

This article is a phased achievement of The National Social Science Fund of China: Research on the blocking mechanism of the critical poor households returning to poverty due to illness, No: 20BJY057.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Kumar, S., Meena, H. M., and Verma, K. (2017). Water Pollution in India: its Impact on the Human Health: Causes and Remedies. Int. J. Appl. Environ. Sci. 12 (2), 275
Google Scholar
Marmot, M., Atinmo, T., Byers, T., Chen, J., and Zeisel, S. H. (2007). Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Nutr. Bull.
Google Scholar
Rabbani, M., Chowdhury, M., and Khan, N. A. (2010). Impacts of Industrial Pollution on Human Health: Empirical Evidences from an Industrial Hotspot (Kaliakoir) in Bangladesh. Asian J. Water, Environ. Pollut. 7 (1), 27
Google Scholar

# data[].attributes.attachment_link.title
Effects of Water Pollution on Human Health and Disease Heterogeneity: A Review

# data[].attributes.attachment_link.description
Background: More than 80% of sewage generated by human activities is discharged into rivers and oceans without any treatment, which results in environmental pollution and more than 50 diseases.

# data[].attributes.attachment_link.readable_text
Lysergic acid diethylamide, commonly known as LSD, is an illegal drug that alters the senses and cause hallucinations.

It was first synthesized in 1938 by a Swiss chemist, Albert Hofman, to treat respiratory depression. In 1943, Hofman accidentally discovered its hallucinogenic properties when he absorbed some through his skin.

Over the next 15 years, LSD was used as an anesthetic and to support psychoanalysis. The counterculture of the 1960s led to it being used for recreational purposes.

As tales of psychedelic "trips," psychotic behavior, and random acts of violence gained media attention, production was stopped, and in 1967, LSD was banned and classified as a Schedule 1 drug with no acceptable medical use. Its popularity has decreased since the 1970s.

It remains illegal in the United States (U.S.) and elsewhere.

Street names include acid, purple haze, dots, and blotter.

Share on Pinterest
LSD is purchased in caps, and only a small amount is required for the effects to take root.

LSD is an illegal, semi-synthetic drug that combines natural and man-made substances. It is derived from ergot, a fungus that grows on certain grains, and a non-organic chemical called diethylamide.

It stimulates serotonin production in the cortex and deep structures of the brain, by activating serotonin receptors.

These receptors help visualize and interpret the real world. The additional serotonin allows more stimuli to be processed that usual. Normally, the brain filters out irrelevant stimuli, but with LSD this is not the case.

This overstimulation causes changes in thought, attention, perceptions, and emotions.

These alterations appear as hallucinations. Sensations seem real, but they are created by the mind.

The perceptions can involve one or more of the five senses. It can also cause blending of the senses, known as synesthesia. People report "hearing" colors and "seeing" sounds.

Users of LSD talk about good or bad "trips," or experiences.

LSD can trigger a range of perceptual changes, often relating to vision, touch, emotions and thinking.

Visual effects include brightened, vivid colors, blurred vision, distorted shapes and colors of objects and faces, and halos of light.

Changes related to touch include shaking, pressure, and lightheadedness.

Mood changes can lead to a sense of euphoria, bliss, peacefulness, dreaminess, and heightened awareness, or despair, anxiety, and confusion. There may be rapid mood swings.

Impact on thinking can lead to a distorted perception of time, either fast or slow, accelerated thoughts, unusual insight or terrifying thoughts, and a sense of transcendence.

LSD is colorless and odorless. A very small amount, equivalent to two grains of salt, is sufficient to produce the drug's effects.

It is taken orally as capsules, pills, sugar cubes, chewing gum, or liquid drops transferred to colorful blotter paper. Recreational dosage averages between 25 to 80 micrograms (mcg).

The onset of hallucinations occurs within 60 minutes, and it can last from 6 to 12 hours.

Physical stimulation resulting from LSD use causes the pupils to dilate, and blood pressure, heart rate, and temperature to rise.

Other short-term effects include:

dizziness and sleeplessness

reduced appetite, dry mouth, and sweating

numbness, weakness, and tremors

However, it primarily affects the mind with visual distortions and sensory hallucinations and illusions.

The danger lies in the unpredictability of the "trip." The potency of the drug is unreliable, and individuals react differently to it.

The user's mindset, surroundings, stress level, expectations, thoughts, and mood at the time the drug is taken, strongly influence the effects of the drug.

Effects can include feelings of well-being, a perception of being outside one's body, an enhanced insight towards creativity, problem-solving, discovering a purpose, and mystical experiences.
A "bad trip," on the other hand, is like a living nightmare. It is similar to psychosis, and the person cannot escape from it. There may be extreme fear, paranoia, a separation from self, and the person may believe that they are dying or in hell.
It can also trigger panic attacks, psychotic episodes, disturbing anxiety, paranoia, pain, and a feeling of dying or going insane.

Severe or life-threatening physical effects are only likely to occur at doses above 400 mcg, but the psychological effects can lead to unusual and risky behavior, potentially resulting in significant injury and death.

As users have no control over the purity of the drug, it is difficult to predict the effect on the body and the mind.

LSD use can lead to long-term mental health problems such as schizophrenia or a psychotic state.

Tolerance, or a need to increase the dose to achieve the desired response, happens quickly. If a specific dose is taken every day for 3 consecutive days, by the third day no reaction will occur.

LSD is not physically addictive, so physical withdrawal symptoms do not occur after stopping use, but psychological addiction can develop.

One of the dangers is that LSD can trigger a long-term psychotic state or induce schizophrenia in susceptible individuals.

Flashbacks, also known as hallucinogen persisting perception disorder (HPPD), and severe disorientation can happen after only one dose.

The reasons for this are unknown.

The production and sale of LSD are illegal in many countries, but some people have called for it to be reclassified.They argue it could be useful for research purposes and for developing clinical applications.

In 2016, researchers proposed using single doses of the naturally occurring hallucinogen, psilocybin, alongside psychotherapy to reduce symptoms of anxiety and depression in patients with life-threatening cancer.

The 29 patients who took the dose experienced lower rates of depression and anxiety for up to 7 weeks, compared with a control group.

No serious cardiac or other adverse effects were observed in these patients, and none of the participants experienced prolonged psychosis or hallucinogen persisting perpetual disorder (HPPD).

# data[].attributes.attachment_link.description
LSD, made from lysergic acid, is a potent, mood-changing chemical. The primary effect of LSD is to alter the senses and cause hallucinations. However, there has been a debate as to whether LSD should be reclassified. This MNT Knowledge Center article looks at the long- and short-term safety of LSD.

# data[].attributes.attachment_link.title
The Effects of Hormonal Birth Control on Your Body

# data[].attributes.attachment_link.description
Birth control isn’t just to prevent pregnancy. The hormones released can also help with cramps, acne, and more. Learn how your body is affected by birth control.

# data[].attributes.body
'The question of taking antidepressants is a weighty one for most creative people.' Many ask, “Will it sap inspiration and cause emotional numbness? Will it turn me into a zombie?”

'There’s also a misconception that taking medication for mental health means a person is weak', But the truth is, medication can often help artists better access their creativity and express their emotions more readily.'

“There’s a misunderstanding that psychiatric medication is in some way going to fundamentally change your personality,” says Madison McCullough, a therapist based in New York City

“I’ve seen how medication can actually allow people to harness some of what they’re going through in their creative process, in a way that can be hard to do if you’re wrapped up in some intense symptoms around whatever you’re coping with.”

# data[].attributes.attachment_link.readable_text
"There's a misunderstanding that psychiatric medication is in some way going to fundamentally change your personality," says Madison McCullough, a therapist based in New York City. "I've seen how medication can actually allow people to harness some of what they're going through in their creative process, in a way that can be hard to do if you're wrapped up in some intense symptoms around whatever you're coping with."

When I was in the depths of depression and bulimia, and my ADHD was undiagnosed, it was nearly impossible for me to get out of bed. If I did experience a jolt of energy, it was incredibly difficult for me to focus. If I was lucky, I'd be able to jot down the main themes of what I wanted to write about, but I would never get far enough to weave them together into something coherent. Medication (I'm currently taking Effexor for depression, Topamax for bulimia, and Adderall for ADHD) hasn't altered my personality; it's made the edges of my depression and anxiety a bit less sharp, so I can more comfortably sort out what I'm feeling.

The truth is, medication can often help artists better access their creativity and express their emotions more readily.

Hayley Cranberry Small, a ceramicist, started taking antidepressants when she wasn't able to make anything at all. "I was at such a low point in my depression. It felt like the only thing to do," she says. "When I'm depressed I don't even want to walk down the street. So I can't imagine creating without being on antidepressants at this point." Small found that taking Effexor, an SNRI (serotonin and norepinephrine reuptake inhibitor), has alleviated some motivational problems and feelings of dread, but she says the matter of dosage is an ongoing conversation with her psychiatrist, as it takes time to figure out what is working.

The issue of taking medication is further complicated by the fact that people can react differently to them. Add to that a laundry list of potential side effects - fatigue (which most associate with that zombie feeling), lowered libido, changes in weight - and it's easy to see why reaching out for help is fraught. Finding the right therapy and the right dosage of antidepressant is crucial. "Artists need to feel feelings in order to be creative. That's how artists express themselves," says Zorica Filipovic-Jewell, a psychiatrist based in New York City. "Some patients experience side effects with medication. That means it's not the right medication for you. When depression is treated well, all the creative parts of your personality return and function at the optimal level."

# data[].attributes.attachment_link.title
How Medication Helps, Rather Than Hinders, My Creativity

# data[].attributes.attachment_link.description
Creative people thrive on emotion, but for those with mental health issues, there's often a fear that treatment with medication (including antidepressants) could dull their most precious resources - including their imagination and creativity.

# data[].attributes.body
Matthieu Bourel - (Artist found in article about creativity)

He does handmade, digital and animated collages.

They are based on the power of images and the diversions resulting from various visual combinations.

'He defines his work as ‘data-ism’, and when mixing elements, he often seeks to evoke a story that, although absent from the known reality, is powerfully present before the viewer and inspires ‘nostalgia for a period in time that never truly existed’.'

The artist intervenes in the mind and memory of the mesmerized audience, distorting realities, enriching or irreversibly eliminating worlds that we find ourselves comfortable living inside them.

A theme that seems to interest Matthieu Bourel is identity, marked by its lack (the absence of the head, for example) or multiplicity.

MY ANALYSIS:

Bourel's work is both surreal and mesmerising as the daunting images portray a certain mindset or thought process - I feel like, for me, this create the exact visuals I imagine when thinking about mental health and anxiety.

# data[].attributes.attachment_link.readable_text
The handmade, digital and animated collages of French artist Matthieu Bourel, currently living and working in Berlin, are based on the power of images and the diversions resulting from various visual combinations. He defines his work as 'data-ism', and when mixing elements, he often seeks to evoke a story that, although absent from the known reality, is powerfully present before the viewer and inspires 'nostalgia for a period in time that never truly existed'.

The artist intervenes in the mind and memory of the mesmerized audience, distorting realities, enriching or irreversibly eliminating worlds that we find ourselves comfortable living inside them. Thus, an ordinary portrait of a woman can easily refresh its meaning when duplicated. The apparently infinite repetition of certain elements is sometimes a commentary on social systems and structures, regarding human behavior and beliefs, revealing hidden intentions and unfolding mask after mask until there is nothing left but a possible truth or at least a more sincere approach to reality, usually filled with irony and tension. Another theme that seems to interest Matthieu Bourel is identity, marked by its lack (the absence of the head, for example) or multiplicity.

'A piece often becomes about the search and desire to combine those emergent narrative symbols that seem charged with a familiar yet distant emotion'. Indeed, we tend to decode the images according to our personal connections, as if the story suddenly speaks about what we fear and the avoidance to confront and understand ourselves, the ego, the other, time and space, now and then.

'Duplicity' (2014)

'Feminism' (2014)

Illustration for the New York Times, Sunday book review.

'Hit the Reset Button in Your Brain' by Daniel J. Levitin.

'Marie Antoinette / Royalty' (2014)

'Politics' (2013)

'Syndicate' (2013)

n.

1. An association of people or firms formed to engage in an enterprise or promote a common interest.

'Generational' (2013)

'Mickey Panzer' (2012)

'Blank' (2012)

adj. blank·er, blank·est

* *

All images © Matthieu Bourel

# data[].attributes.attachment_link.title
Matthieu Bourel: Collage and the power of images - The re:art

# data[].attributes.attachment_link.description
The handmade, digital and animated collages of French artist Matthieu Bourel , currently living and working in Berlin, are based on the power of images and the diversions resulting from various visual combinations.

# data[].attributes.body
Deandra Lee’s self-portrait photography features scenes with birds, rain, flowers, and other natural elements.

Her photos show a surreal interpretation of each emotion. Often incorporating symbolic birds associated with freedom and clouds representing moods.

She brings feelings of curiosity and helps people experience what these emotions feel like.

# data[].attributes.attachment_link.title
Artist inspiration: How Deandra Lee creates collages with feeling

# data[].attributes.attachment_link.description
‍Hi Deandra! Tell us all a bit about yourself and your art background.I’m 21 now and started my art journey when I was 13. I’m an introvert and learned on my own - I never had any photography and I didn’t know much about the art world and what it had to offer. Around that time I had a love for dolls…

# data[].attributes.body
Metz’s colorful digital creations feature medicine, sweet treats, retro signs, and objects.

He focuses on pills, their colorful artwork is full of commentary on medicating in society.

Labeling each capsule with a different prescription, they emphasize on the narrative of people buying a way to get happy, looking for a way to get better sleep, or taking something to feel love.

# data[].attributes.attachment_link.readable_text
If you are looking for an easy way to start an art collection, fine art prints are a great place to begin, here are a few reasons why. First, it is a low dollar investment that allows you to test the waters of what it is like to own an art collection. Don't get me wrong, collecting original art is much more enjoyable, but it is not always the most practical way to start an art collection. Fine art prints allow you to try out what your collecting taste and style are. You can easily create a small gallery wall with multiple artworks and determine where to go from there. You can always look for artists like myself, who use their creativity in several styles that tie together to give a broad and unified start to your collection.

# data[].attributes.attachment_link.description
Fine Art Prints at an affordable price with free shipping. Jaymie Metz offers vibrant, colorful, high quality works of art to help you start collecting fine art. Come take a look at my wide variety of fine art.

# data[].attributes.body
'Various symptoms are described in van Gogh's letters and other documents such as the asylum register at Saint-Rémy. The symptoms include: poor digestion and a bad stomach, hallucinations, nightmares, manic episodes, depressive episodes, stupor, absent-mindedness, impotence, insomnia, and anxiety.'

# data[].attributes.attachment_link.readable_text
After his admission to the institution in Saint-Rémy, Vincent often mentions death in his letters. His ambition and faith in his own health gradually also starts to wane. Vincent is petrified that the attacks he suffered will return.

Conversely, his brother is bursting with ambition. Theo was married, had recently become a father and was planning on starting his own art dealership. Vincent was still completely financially dependent on Theo, and perhaps felt like a millstone around his brother's neck. Or perhaps he was worried that Theo would not be able to continue to send him sufficient funding in the future.

We'll probably never know the exact reason for sure.

# data[].attributes.attachment_link.title
Why Did Vincent van Gogh Commit Suicide?

# data[].attributes.attachment_link.description
Discover the answers to the frequently asked questions about Vincent van Gogh.

# data[].attributes.body
Vincent Van Gogh's mental health can be displayed through his use of images, colours and portrait expressions.

# data[].attributes.attachment_link.readable_text
About Van Gogh's psychiatric disorder

Use the up and down keys to compare the two images.

Difference of Opinion

The difference of opinion between the two friends is clearly visible in these two works. You could see them as portraits of the artists.

In Vincent's painting Gauguin's Chair, the lamp, candlestick, and the book refer to the nocturnal dream world, and therefore to the imagination. In Van Gogh's Chair, the onions represent nature, i.e. painting from reality.

Ear

The situation came to a head on 23 December, 1888. After a heated argument, Vincent, in utter confusion, cut off his left ear.

He wrapped his ear in paper and took it to a prostitute in the village. The girl fainted and the entire brothel was in commotion. They called the police, who found the artist at his home the following morning. Vincent was hospitalised, and Gauguin returned to . The dream was shattered.

There was an article in the local newspaper about the incident.

In addition to two self-portraits of him with his bandaged ear, Vincent created this still life with onions.

He included mostly personal objects, such as his pipe and tobacco. Placed beside these are the envelope of a letter by his brother Theo, an empty bottle of absinthe, and a popular handbook that he consulted for self-medication.

'Now the shock had been such that it disgusted me even to move, and nothing would have been so agreeable to me as never to wake up again. At present this horror of life is already less pronounced, and the melancholy less acute. But I still have absolutely no will...'

He also wrote about other people in the hospital. At first, Vincent was afraid of them. They could sometimes be heard shouting in the corridors. But in the end, the sight of and contact with these fellow patients offered him comfort and reassurance.

'I observe in others that, like me, they too have heard sounds and strange voices during their crises, that things also appeared to change before their eyes. And that softens the horror that I retained at first of the crisis I had... Had I not seen other mad people at close hand I wouldn't have been able to rid myself of thinking about it all the time.'

Use the up and down keys to compare the two images.

Time to Leave

Vincent began to feel increasingly trapped at the psychiatric hospital and wanted to leave as soon as possible.

After a year, in May 1890, he left for Auvers in northern France. There, he was closer to Theo, who lived in Paris. Dr Gachet from Auvers was asked to take care of him.

# data[].attributes.attachment_link.title
Vincent's Illness and the Healing Power of Art

# data[].attributes.attachment_link.description
Vincent van Gogh was 35 years old when he cut off his left ear just before Christmas, 1888. How did he deal with the uncertainties of his mental condition during this difficult time?

# data[].attributes.body
In 1988 the pharmaceutical firm Eli Lilly and Company introduced Fluxotine.

Fluxotine was a new type of antidepressant that was safer and more effective than those of previous eras.

The development of this groundbreaking drug was undertaken by three Eli Lilly researchers: Ray Fuller, David Wong, and Bryan Molloy.

During the 1950s a class of antidepressants known as tricyclics was developed. Although effective, these drugs also cause a variety of undesirable side effects, including dizziness, blurred vision, and constipation.

The next generation of antidepressants was known as monoamine oxidase inhibitors, or MAOIs. Unfortunately, MAOIs can be highly toxic.

Further research was needed to develop an effective antidepressant with low toxicity and a low incidence of side effects. A significant breakthrough occurred in 1974, when Eli Lilly scientists reported on their studies of fluoxetine, the first in a class of antidepressants known as selective serotonin-reuptake inhibitors, or SSRIs.

Most antidepressants increase the amount of neurotransmitters in the brain. Neurotransmitters are the chemicals released by nerve cells to stimulate neurons, thereby passing impulses through the nervous system.

It is believed that depression is especially affected by levels of the neurotransmitters serotonin and norepinephrine.

Antidepressants differ in respect to which neurotransmitters they increase and how they do it.

MAOIs inhibit the enzyme monoamine oxidase from destroying the neurotransmitters norepinephrine, serotonin, and dopamine - increasing the levels of all three.

Tricyclics reabsorb, for reuse, of norepinephrine and serotonin already released in the brain. This means that greater amounts of these neurotransmitters are left in the brain, increasing their effects. They affect the neurotransmitter acetylcholine, which causes a variety of side effects.

SSRIs are like tricyclics, except that they are more selective; by affecting only serotonin, they generally cause fewer side effects. SSRIs are rarely lethal in overdoses.

Prozac hit the market in 1988, to much fanfare among doctors and patients alike. It was as effective as other antidepressants on the market but did not induce as many side effects. Since then Prozac has also been shown to be effective in treating other conditions, including obsessive-compulsive disorder and bulimia nervosa.

# data[].attributes.attachment_link.readable_text
In 1988 the pharmaceutical firm Eli Lilly and Company introduced Prozac (fluoxetine), a new type of antidepressant that was safer and more effective than those of previous eras. The development of this groundbreaking drug was undertaken by three Eli Lilly researchers: Ray Fuller, David Wong, and Bryan Molloy.

Prozac and similar drugs have proven effective for many of the estimated 15 million people in the United States suffering from depression. Although questions were raised early on about certain side effects and its true level of efficacy, Prozac quickly became one of the most prescribed antidepressants, with Eli Lilly's worldwide annual sales reaching the $2 billion to $3 billion range until the expiration of its patent in 2001 and the rise of competition from other pharmaceutical companies, ultimately including manufacturers of generic drugs.

Antidepressants and How They Work

During the 1950s a class of antidepressants known as tricyclics was developed. Although effective, these drugs also cause a variety of undesirable side effects, including dizziness, blurred vision, and constipation. The next generation of antidepressants was known as monoamine oxidase inhibitors, or MAOIs. Unfortunately, MAOIs can be highly toxic. Further research was needed to develop an effective antidepressant with low toxicity and a low incidence of side effects. A significant breakthrough occurred in 1974, when Eli Lilly scientists reported on their studies of fluoxetine, the first in a class of antidepressants known as selective serotonin-reuptake inhibitors, or SSRIs.

Most antidepressants work in the same manner: they increase the amount of neurotransmitters in the brain. Neurotransmitters are the chemicals released by nerve cells to stimulate neurons, thereby passing impulses through the nervous system. It is believed that depression is especially affected by levels of the neurotransmitters serotonin and norepinephrine.

Antidepressants differ in respect to which neurotransmitters they increase and how they do it. MAOIs inhibit the enzyme monoamine oxidase from destroying the neurotransmitters norepinephrine, serotonin, and dopamine, thereby increasing the levels of all three. Tricyclics inhibit the reuptake (reabsorption), for reuse, of norepinephrine and serotonin already released in the brain. This means that greater amounts of these neurotransmitters are left in the brain, increasing their effects. Tricyclics also often affect the neurotransmitter acetylcholine, which causes a variety of side effects. SSRIs work much like tricyclics, except that they are more selective; by affecting only serotonin, they generally cause fewer side effects. Furthermore, SSRIs are rarely lethal in overdoses.

Fuller Focuses on Serotonin

© Copyright Eli Lilly and Company. All rights reserved. Used with permission.

The story of Prozac begins in the 1960s, when Ray W. Fuller (1935-1996) came to work at Eli Lilly. Fuller was born and raised in Illinois. He earned a bachelor's degree in chemistry in 1957 and a master's degree in microbiology in 1958, both from Southern Illinois University. Fuller worked his way through college as an employee at a state mental hospital; there he developed his interest in the brain and therapies for treating mental disorders.

In 1961 he earned his doctorate in biochemistry from Purdue University. Shortly thereafter he accepted a post as director of the biochemistry research laboratory at the now defunct Fort Wayne State Hospital for developmentally disabled children. In 1963 he joined Eli Lilly as a pharmacologist and was set to work testing potential new antidepressants.

In his research Fuller had used rats treated with chloroamphetamine, which inhibited the production of serotonin, to measure the effects of other drugs on serotonin levels. Fuller believed that this method would forward research on brain chemistry and sought to entice Bryan Molloy, another Eli Lilly scientist, to this line of research.

Molloy Chooses Mind over Heart

Bryan B. Molloy (1939-2004) was born in Broughty Ferry, Scotland. He received his bachelor's degree in chemistry in 1960 from the University of St. Andrews, and three years later earned his doctorate in chemistry from the same institution. In 1963 he came to the United States to conduct postdoctoral research at Columbia and Stanford Universities, and three years later joined Eli Lilly as a senior organic chemist. Molloy's research interests centered on the neurotransmitter acetylcholine and its effect on the heart. Fuller suggested that he abandon his cardiac work and take up a related line of research: looking for an antidepressant that did not affect acetylcholine. A new medication with that trait would not have many of the side effects that tricyclics had.

After accepting this proposal Molloy began to research possible compounds for his project. Knowing that antihistamine research had led to some of the first antidepressants, including chlorpromazine, Molloy developed compounds whose chemical structures closely resembled those of antihistamines.

Wong Joins the Team

David T. Wong (b. 1935), another Eli Lilly researcher with an interest in neurochemistry, joined the antidepressant project in 1971. Born in Hong Kong in 1935, Wong was the son of a machinist. As a youth he was encouraged by his family to find a career helping people. He began his higher education at National Taiwan University, majoring in chemistry, and in 1957 he traveled to the United States to study at Seattle Pacific College, where he earned his bachelor's degree in chemistry in 1960. In 1964 Wong earned a master's in biochemistry from Oregon State University. Two years later he received his doctorate in biochemistry from the University of Oregon. He joined Eli Lilly as a research biochemist in 1968.

Fluoxetine Discovered

In 1971 both Molloy and Wong attended a lecture at Eli Lilly on neurotransmission given by Solomon Snyder, a researcher from Johns Hopkins University. Snyder had developed a technique that would prove immensely useful to the Lilly team. He had ground up rat brains, separated out the nerve endings, and created an extract of nerve endings that worked in the same way as living nerve cells.

Wong used this technique to test the effects of Molloy's compounds, one of which was found to block the reuptake of serotonin while affecting virtually nothing else. The compound was further tested in Fuller's chloroamphetamine-treated rat and was again found to block the reuptake of serotonin. This compound was fluoxetine.

Prozac hit the market in 1988, to much fanfare among doctors and patients alike. It was as effective as other antidepressants on the market but did not induce as many side effects. Since then Prozac has also been shown to be effective in treating other conditions, including obsessive-compulsive disorder and bulimia nervosa.

# data[].attributes.attachment_link.title
Ray W. Fuller, David T. Wong, and Bryan B. Molloy

# data[].attributes.attachment_link.description
Three pharmaceutical researchers working at Eli Lilly in the 1980s changed the treatment of depression with their invention of Prozac.

# data[].attributes.attachment_link.title
Bristol based portrait, landscape and mural artist — GEORGE J HARDING

# data[].attributes.attachment_link.description
As an artist, I see my work as an integral part of my mental health recovery, celebrating and transcending these difficulties and differences through creativity.

# data[].attributes.body
90% of the serotonin our body makes is in the gut, so maybe we should be looking at healing that?

# data[].attributes.attachment_link.embed_code
@itsdrwes
#drwes #mentalhealth #depression #antidepressants
♬ original sound - Dr Wes Tensel

# data[].attributes.body
Depression is labelled as low serotonin levels.

90% of serotonin is made in the gut so a good balanced diet will help!

SSRI's don't increase serotonin.

# data[].attributes.attachment_link.title
Why SSRIS don’t work #garybrecka #mentalhealth #depression #seratonin #dopamine 

# data[].attributes.attachment_link.embed_code
@brecka.clip
Why SSRIS don’t work #garybrecka #mentalhealth #depression #seratonin #dopamine
♬ original sound - Brecka

# data[].attributes.attachment_link.title
Gary Brecka explains the truth behind depression and antidepressants #garybrecka #mentalhealth #depression #mindset #health #fitness 

# data[].attributes.attachment_link.embed_code
@garybrecka.shorts
Gary Brecka explains the truth behind depression and antidepressants #garybrecka #mentalhealth #depression #mindset #health #fitness
♬ apathy - Øneheart