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ตัวแปรที่สนใจ

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ตัวแปรที่สนใจ

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ประสบการณ์เชิงลบในวัยเด็ก (Adverse childhood experiences) ที่มีความสัมพันธ์ต่อโรคไบโพล่าร์ในวัยรุ่น

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เปิดเพลงเพื่อสร้างบรรยากาศผ่อนคลาย

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เปิดเพลงเพื่อสร้างบรรยากาศผ่อนคลาย

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4K Cozy Coffee Shop with Smooth Piano Jazz Music for Relaxing, Studying and Working

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บรรยากาศหอมกลิ่นกาแฟ

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บรรยากาศหอมกลิ่นกาแฟ

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เติมของหวานเล็กน้อย

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เติมของหวานเล็กน้อย

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ประสบการณ์สะเทือนใจและโรคไบโพลาร์ในกลุ่มชาติพันธุ์ต่าง ๆ

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ประสบการณ์สะเทือนใจและโรคไบโพลาร์ในกลุ่มชาติพันธุ์ต่าง ๆ

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. Author manuscript; available in PMC: 2024 Aug 1.

Abstract

We examined the presence of adverse events in both childhood and adulthood and the prevalence of PTSD in individuals with Bipolar Disorder (BD). There were 191 adults diagnosed with BD Type I and 924 controls, of predominantly African Ancestry (AA). All were administered the GPC-Screening Tool and the BD group the DIPAD. In addition Childhood adversities were measured using the ACE (from 0-10), about traumatic events before age 18 and lifetime adversities were measured with 15 questions adapted from the Study of Addiction: Genetics and Environment (A-SAGE (from 0 to 15) for all cases and controls. Probable PTSD (pPTSD) was measured with 4 questions on the GPC screener. Sum scores were calculated for the ACE and A-SAGE by tallying positive responses. Odd Ratios (OR) were used to measure the association between BD and Controls exposure to adversity. BD was associated with a significantly higher mean ACE score and A-SAGE score compared to controls. There was a significantly higher prevalence of pPTSD in the BD (54.5%) versus Controls (6.6%) as well. Greater OR's were seen in the BD compared to Controls for each ACE question (p<0.05). Results were similar for A-SAGE. Limitations include possible recall bias, and missing data.

Keywords: Bipolar Disorder, adverse events, trauma, PTSD, parental psychopathology, abuse and neglect, African Ancestry (AA)

1. Introduction

Literature over the last few decades has suggested that the susceptibility of Bipolar Disorder (BD) is most likely due to a complex interaction between genetic and environmental risk factors ( Etain et al., 2008; McGuffin et al., 2003). Previous research has demonstrated a strong correlation between life stressors and the risk of developing and sustaining episodes in BD ( Gershon et al., 2013). A meta-analysis of forty-two studies informed that individuals with BD report having more stressful life events than healthy individuals and to physically ill individuals ( Lex et al., 2017). Moreover, the severity of the negative events have been found to predict worse illness course, slower recovery and higher rate of relapse ( Etain et al., 2008; Gershon et al., 2013).

Among all different types of adversities, childhood adverse events are significantly more common among these patients than in the general population, with emotional abuse most strongly correlated ( Palmier-Claus et al., 2016). Estimates of childhood adverse events have varied from 25-75% of BD individuals, and over one third have experienced more than one form of adversity ( Dualibe and Osório, 2017; Garno et al., 2005; Leverich et al., 2002). These early stressors, either individually or in combination, have also led to greater disease-related morbidity and mortality, most notably earlier onset and longer duration of illnesses, greater number of inpatient hospitalizations, more lifetime suicidal ideation, suicide, and co-morbid substance use disorders ( Brown et al., 2007; Carballo et al., 2008; Garno et al., 2005; Leverich et al., 2002; Marchand et al., 2005; McIntyre et al., 2008; Park et al., 2020; Quidé et al., 2020; Romero et al., 2009; Rowe et al., 2023; Young and Juruena, 2021).

Considering the correlation between adverse events and BD, not surprisingly, evidence has also suggested that BD and Post-traumatic Stress Disorder (PTSD) often co-occur, thus worsening the disease course and complicating the treatment. While PTSD was found in 8% of the general population, up to 40% BD patients were found to have PTSD ( Cerimele et al., 2017; Hernandez et al., 2013; Otto et al., 2004; Rowe et al., 2023). While there is ample literature on early life stressors and BD, the impact of adverse events over the lifetime of individuals with BD is less studied. Research to date has looked more broadly at negative life events and chronic stressors, as opposed to specific types of traumas from both childhood and adulthood. Moreover, research on patients with BD has an overall theme of co-occurring anxiety disorders and only recently has there been a specific focus on co-occurring PTSD and BD.

Current studies on childhood trauma in bipolar disorder primarily focus on individuals of European Ancestry (EA) ( Etain et al., 2017; Van Bergen et al., 2019) or do not stratify findings by race/ethnicity ( Upthegrove et al., 2015). AA with BD also tend to have a greater number of inpatient hospitalizations and more suicide attempts than EA ( Kupfer et al., 2005). The role of childhood trauma in this population could provide valuable information that could aid clinicians in improving functional outcomes.

This study examines the number of adverse events, from both childhood and adulthood, and prevalence of PTSD in a sample of individuals with BD, as compared to controls matched by age, and sex. The majority of our sample population consists of AA, and we plan to compare our data to what has been reported in cases and controls of EA in the literature.

2. Methods

2.1. Participants

Participants are a part of the larger ongoing Genomic Psychiatry Cohort (GPC) research study ( Pato et al., 2013). The participants of GPC research consist of individuals diagnosed with schizophrenia (SZ), schizoaffective (SA) and bipolar disorder (BD), and control participants with no personal or family psychiatric history, in first- or second-degree relatives, of BD or SZ. This analysis included 191 cases, diagnosed with BD I and 924 controls all over age 18 y/o. All participants received the ACE and the A-SAGE in addition to the GPC screening tool, a self-report measure that is validated by the interviewer. The screener consisted of 32 questions and asks general yes/no questions about psychiatric history for psychosis, mania, depression, panic disorder, PTSD, OCD and substance use history. DIPAD, a semi-structured clinical interview, was also conducted for participants with BD to assess their clinical symptoms. Participants were recruited in hospital waiting rooms, outpatient clinics, health fairs, community outreach activities and online advertising. All the procedures were reviewed and approved by the relevant IRB and all participants signed informed consent.

2.2. Measures

Childhood adverse events were evaluated using ACE questionnaire, a 10-item, well-validated self-report survey ( Dube et al., 2004; Felitti et al., 1998). It asked negative experiences prior to the age of 18, including physical and emotional abuse, physical and emotional neglect, and family dysfunctions. What distinguishes the ACE questionnaire from other measures is that all participants were asked to only recall their pre-adult (age <18) exposure to select adverse events, which contrasts with other tools that look at these events throughout respondents' lifetime. By consolidating all respondent ages as a pre-adult group, ACE removes age as a confounding factor since all participants in this study are over age 18 so all have lived thru the ACE period. However in the A-SAGE, the likelihood of adverse events occurring is logically higher as people live more years, so this can be present a bias for the A-SAGE. In addition, the test-retest reliability of the ACE also indicates that there is consistency of participants' responses despite time lapse between the childhood events and the research survey ( Dube et al., 2004).

Lifetime adverse events were evaluated with 15 questions adapted from Study of Addiction: Genetics and Environment (SAGE). For consistency with the ACE questionnaire and limited exposure in this sample to military trauma, these questions were removed from this analysis. Even with these changes, the modified Adversity SAGE (A-SAGE) includes some different types of adverse events from the ACE. Only questions 4 and 5 in A-SAGE are related to sexual trauma, which were included in the ACE. The A-SAGE also asks at what age the adverse events first happened and the total number of times the event happened up to the day of the interview. Thus, it can provide a quantitative measure of lifetime severity, though it does add some bias related to the varied age of adult subjects at the time of interview. For these complementing strengths both instruments were used.

Probable PTSD:

The GPC screening tool consisted of 32 items and 4 of them are used in this study since they are related to the symptoms and diagnosis with PTSD. Subjects were identified as "probable PTSD" if they answered "yes" to all four questions. The 4 questions are:

32.Have you ever experienced a traumatic event in which you felt that your life might be in danger? (Examples: serious car or other accident, natural disaster [like earthquakes or hurricanes], being physically attacked or threatened with a knife or gun, being sexually assaulted or raped, experienced combat or been in a war zone, or observed sudden violent death [homicide or suicide].)"

32a.Sometimes images or strong memories of traumatic events keep coming back in flashbacks, thoughts that you can't get rid of, or repeated nightmares. Has that Ever happened to you?

32b.Did you make a special effort to avoid thinking or talking about what happened or deliberately stayed away from things or people that reminded you of the terrible experience?

32c.After this experience did you have trouble sleeping, have difficulty concentrating, were unusually irritable, have outbursts of anger, felt overly watchful or on guard, or been very jumpy or easily startled?

2.3. Data Analysis

The data were analyzed with SPSS for Windows (version 24, SPSS Inc., Chicago, IL, USA) and are provided as percentages, means, medians, and standard deviation (SD). Sum scores were created for the ACE and A-SAGE questionnaires by totaling the number of positive responses to each question type. ACE scoring ranges from 0-10 and A-SAGE scoring ranges from 0-15. Odd Ratios (OR) were used to measure the association between the exposure on the ACE and the presence of BD.

3. Results

3.1. The prevalence and impact of adverse life events (Table 1)

Table 1.

BD
N=191

Controls
N=924

Significance

The total sample size was 1,115 individuals. Approximately 17% were BD cases and 83% were control subjects. The study took place in an underserved neighborhood in Brooklyn, New York, and participants consisted of 71% African ancestry (AA), 8.6% European ancestry (EA) and all other races or mixed races totaling 20%.

The ACE (Adverse Childhood Experiences) average sum score (from 0 to 10) was compared among the two groups. The average sum score for the BD group was significantly higher (M=4.15) than the Control group (M=1.11). This indicates that participants in BD group have experienced more types of traumatic events growing up compared to control group. The A-SAGE average sum score, over one's lifetime, (from 0 to 15) was also compared among the two groups. The average score for the BD group was also significantly higher (M= 3.97) than the Control group (M=1.75).

It should also be noted that there is a notably high percentage of BD group with probable PTSD (54.5%) compared to control group (6.6%). This shows that probable PTSD diagnosis is associated with BD diagnosis, as well as higher ACE score and A-SAGE score.

3.2. The childhood adverse experience profile of BD and control group with the ACE (Figure 1 and Table 2)

Figure 1.

ACE Questionnaire Responses by Diagnosis

Table 2.

BD N= 191 (%)

Control N=924 (%)

Odds Ratio (95% CI)

ACE Q1 - Did a parent or other adult in the household often or very often...
Swear at you, insult you, put you down, or humiliate you? Or Act in a way that made you afraid that you might be physically hurt? YES

104 (54.5%)

114 (12.3%)

8.49 (6.01, 12.00)*

ACE Q6 - Were your parents ever separated or divorced?
Yes

114 (59.7%)

310 (33.5%)

2.93 (2.13, 4.04)*

ACE Q7 - Was your mother or stepmother:
Often or very often pushed, grabbed, slapped, or had something thrown at her?
Or Sometimes, often, or very often kicked, bitten, hit with a fist, or hit with something hard? or Ever repeatedly hit over at least a few minutes or threatened with a gun or knife? Yes

53 (27.7%)

48 (5.2%)

7.01 (4.56, 10.77)*

ACE Q8 - Did you live with anyone who was a problem drinker or alcoholic, or who used street drugs? Yes

88 (46.1%)

118 (12.8%)

5.84 (4.14, 8.23)*

ACE Q10 - Did a household member go to prison? Yes

57 (29.8%)

100 0.8%)

3.51 (2.41, 5.09)*

For each item on the ACE, a greater OR was seen in the BD group compared to the control group, indicating that there is a higher ratio of BD participants experiencing childhood trauma for every single traumatic event listed under ACE ( Table 2).

The difference between BD and control group is quite noteworthy, since it can be seen that the percentage of ACE events in BD group range from 23.6% to 59.7% while all of the ACE items in control groups are each around 10%, with parental separation being the only exception ( Figure 1).

Parental separation is the most common childhood adversity reported in both BD (57.9%) and control group (33.5%). For participants with BD, emotional and physical abuse and neglect are also common and are indicated by a high prevalence in BD: swear/insult/put down/humiliate (54.4%), push/grab/slap/throw (50.8%) and not feeling loved or important (48.2%), living with anyone who uses substance (46.1%) ( Figure 1).

All OR were elevated in the BD subjects. For instance, those with BD compared to controls were 15 times more likely to have a household member mentally ill or depressed than control subjects. BD cases were also 9 times more likely to experience physical abuse and 8 times more likely to experience emotional abuse, emotional neglect, and physical neglect. ( Table 2)

3.3. The lifetime traumatic experience profile of BD and control group with the A-SAGE (Table 3)

Table 3.

BD (N= 191) % (N)

Control (N=924) % (N)

Odds Ratio (95% CI)*

As with the ACE questionnaire, responses to the A-SAGE in the BD group were compared to those in the control group. There was a higher odds of each traumatic event in the BD group compared to controls, except for question 11, which asked about radiation exposure and was very rare in both groups equally ( Table 3).

Patients with BD were 9 times more likely to have been held captive, tortured, or kidnapped than controls ( Table 3). However, it is important to note that positive responses to A-SAGE Q9 was only 2% (N=18) for control and 16% (N=30) for BD. BD patients were also 7 times more likely to have been sexually assaulted by an individual who was not related to them as compared to Controls ( Table 3).

The most common traumatic events experienced were unexpected death of close friend/relative (BD = 66%, control = 44%) and mugged, threatened with weapon, robbery (BD = 49%, control = 21%).

4. Discussion

In concordance with current literature, our research found that individuals with BD bipolar were significantly more likely than controls to have both childhood and adulthood adverse events ( Bergink et al., 2016; Daruy-Filho et al., 2011; Gershon et al., 2013; Palmier-Claus et al., 2016). Compared to the control group, BD group was observed to have experienced not just more types of adverse events but to have a higher probability of PTSD diagnosis. Greater OR was seen in BD group compared to control group for each ACE question and each A-SAGE question, with the exception of radiation exposure.

When looking at ACE, our study found that parental psychopathology has the highest odds ratio ( Table 2). The increased risk of BD in offspring of parents with mental illness could be multifaceted. Parents' psychopathology (ACE Q9) could impair their ability to provide ample emotional and physical support to their offspring ( Bergink et al., 2016; Singh et al., 2007). Families with parents with mental illnesses, especially mood disorders, can have less cohesion, less organization and more conflict when compared to control families ( Chang et al., 2001). Alternatively, the strong correlation between parental psychopathology and BD can also supports the genetic component of BD. Bergink et al. (2016) conducted a large cohort study that included over 980,000 people from Denmark on the impact of childhood adverse life events, especially parental psychopathology, in BD. They found that parental psychopathology has a strong independent effect on developing BD later in life, even when all other adversities were absent. Even though our research cannot fully quantify the influence of genetics vs environmental factors in the progression of BD, recognizing and acknowledging parental psychopathology as one of the most influential adversities from childhood that can impact the progression of BD can give directions to future research.

Apart from parental mental health, it can be noted in ACE that physical abuse, emotional abuse, physical neglect, and emotional neglect are adverse events from childhood that have relatively high OR ( Table 2 and figure 1). In comparison, adversities or traumatic experience related to dysfunctional household, including parental divorce or separation, living with substance user, household member going to prison, though still have OR more than 1, but not as great. Moreover, Carbone et al. (2019) conducted a two-step cluster analysis with participants with BD and SZ. Similar to ACE, the Childhood Experience of Care and Abuse scale (CECA), which also looks at physical abuse and neglect, emotional abuse and neglect, sexual abuse and familial dysfunction, was administered to evaluate adverse childhood experiences. Carbone et al. (2019) found that childhood traumatic experiences of abuse and neglect are correlated with higher presence and severity of clinical symptoms, such as more psychotic features and longer duration of illness. A meta-analysis also concluded that the effect of emotional abuse has a particularly high association with BD (OR=4.04 CI 3.12-5.22) among all types of childhood adversity measured ( Palmier-Claus et al., 2016). In this way, certain childhood traumatic experience can help us identify individuals with higher risk of developing BD and more complex and severe clinical features.

Perhaps most striking amongst the results of the A-SAGE are the largest OR for item A09, rape and sexual assault by not related person (OR=7.21), and item A13, being held captive, tortured or kidnapped (OR=9.38) ( Table 3). While these questions may have been interpreted variably by the study subjects, they are different from other questions in the A-SAGE and the ACE in that they likely refer to circumstances that are both dangerous and unfamiliar. One possible explanation for the high OR for these questions may be the frequently replicated finding of trait impulsivity in patients with BD in both euthymic and manic states compared to controls ( Peluso et al., 2007; Rote et al., 2018; Strakowski et al., 2010; Swann et al., 2003). Moeller et al. (2001) pointed out that the embodiments of impulsivity in psychiatric disorders include a lack of consideration for consequences of behaviors and reactions to stimuli before fully processing of information. Individuals with BD may therefore have a higher likelihood than those without BD of findings themselves in more dangerous and unfamiliar situations where they might be attacked or otherwise traumatized by a stranger. However, it should be noted that different measures of impulsivity have been used in the literature and have yielded inconsistent outcomes ( Moeller et al., 2001). Reddy (2014) measured self-reported impulsiveness with the Barratt Impulsiveness Scale (BIS) and compared it to the results from the Balloon Analogue Risk Task (BART), a computerized game with predicative validity of real-world risk-taking behaviors. Reddy pointed out that individuals with BD may perform similarly to controls on BART, a more objective measure, even though they may score significantly higher on BIS, a self-reported measure ( Reddy et al., 2014). As a result, future research may consider the joint use of self-reported and objective measures to explore the multiple facets of impulsivity in BD.

When comparing the OR of sexual abuse, physical neglect, emotional neglect, parental loss, or physical abuse in BD groups versus controls in both ACE and A-SAGE, our cases had a greater OR of experiencing these events than what has been reported in other studies and meta-analyses ( Palmier-Claus et al., 2016; Upthegrove et al., 2015). After examining 19 papers, Palmier-Claus reported that childhood emotional abuse was found to have a strong effect in BD with an OR of 4.04, (OR=4.04, 95% CI 3.12-5.22) ( Palmier-Claus et al., 2016). Our data show that the responses to question 4 in ACE, the question related to emotional abuse, has a much higher OR (8.11, 95% CI 5.69-11.56). Similarly, when maltreatment - including physical abuse, sexual abuse, or rape - was examined in BD population in a group of participants consisting of 3% AA and 74% EA, it was found that BD population has an OR=2.53 (95%1.68-3.82) ( Grandin et al., 2007). In our ACE, question 2, corresponding to physical abuse, has an OR of 9.11; question 3, corresponding to sexual abuse, has an OR of 6.70 and Question A08 and A09 in A-SAGE, corresponding to rape, have OR of 5.06 and 7.21, respectively. This is likely because the majority of our participants were recruited from an underserved neighborhood in Brooklyn and the majority of our participants are of African Ancestry (AA). Studies have consistently shown that AA experience more violent crime in their lives than other racial or ethnic groups ( Ullman, 2021). AA have an exceedingly high rate of trauma exposure (≥65%) compared to EA, including physical assault, sexual assault, and various forms of intimate partner violence ( Alim et al., 2006). In fact, AA adults overall report around twice as many adverse childhood experiences as white adults as per the ACE questionnaire ( Sheats et al., 2018). However, the gap between the experiences of AA and EAadults aged 18-34 is widest for outcomes with the greatest immediate risk to physical health, such as aggravated assault and physical fights leading to injuries ( Sheats et al., 2018). These data may together explain the divergence in OR when it comes to the more violent crimes. However, since the majority of both our cases and controls in this study were of AA, we cannot compare our results from the ACE and A-SAGE with an EA population in this same community but only make reference from the existing literature. This emphasizes the importance of this work in characterizing the AA experience since previous work is largely focuses on European ancestry and this work highlights the difference in a Bipolar versus control sample who are predominantly of AA.

5. Limitations

There are several limitations in the current study. First, as mentioned, our sample was collected as part of an ongoing African Ancestry collection in Brooklyn, NY. The ACE and A-SAGE collection was one of convenience so, generalizability is limited. As a result, even though we have a majority (57.6% BD of 191) and 74.2% controls of 924) of participants being AA, the conclusion about the impact of AA descent on developing PTSD as well as ACE and A-SAGE scores cannot be conclusive because of sample size between cases and controls. However,this is an important first step in addressing the dearth of data on African Ancestry in case and control samples.

Second, it should be noted that there was a large amount of missing data reported from the A-SAGE, related to first age and frequencies of adverse events, this limits our conclusions from the A-SAGE. Because of the amount of missing data, the results on age and frequencies may be skewed and thus are not analyzed. This missing data could be a consequence of participants' inability or unwillingness, to recall or answer. Even though research has shown that adversity reported by patients with mental illnesses are surprisingly reliable ( Brown et al., 2007; Carbone et al., 2019), retrospective study have yielded recall bias due to memory deficiencies ( Gorin and Stone, 2001). Self-reported questionnaires may also be related to participants' subjective interpretation and result in either overestimation or underestimation of the adverse events that occurred ( Koenders et al., 2014; Powers et al., 2016). As a result, compared to A-SAGE, ACE appears to be a more powerful tool, since it has a simple Yes/No answer, without further details except for a clear age cutoff, before 18yo. Future studies utilizing A-SAGE will need more diligence in completion of missing self-reported items for a more robust and informative data set.

Despite limitations, our research has shown an increased prevalence of lifetime adverse events and PTSD in populations diagnosed with BD. We identified adverse events with higher OR for individuals with BD, which suggests certain adverse events are more impactful on progression of BD. Clinicians working with BD patients should be aware of the high prevalence of lifetime adversity of patients and comorbidity of PTSD. The exploration of past traumatic experience can allow clinicians to gain a better clinical picture of the patients' conditions, and even help them to decide whether a trauma-informed treatment module could be beneficial.

Highlights:

Individuals with BD reported having experienced more childhood and lifetime adverse events.

Individuals with BD had a higher prevalence of pPTSD

Among all the ACE questions, parental psychopathology has the highest OR.

Physical abuse, emotional abuse and emotional neglect also had relatively high OR.

Acknowledgements:

We would like to acknowledge all the GPC collection sites for their efforts with data collection.

Funding:

This work was supported by the National Institute of Mental Health [R01MH104964, 2015]

Role of the Funding Source:

National Institute of Mental Health - participant enrollment and data analysis

Footnotes

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Conflict of Interest Statement

The authors have no conflicts of interest to declare.

References

1. Gorin A, Stone A, 2001. Recall biases and cognitive errors in retrospective self reports: A call for momentary assessments

2. Grandin LD, Alloy LB, Abramson LY, 2007. Childhood Stressful Life Events and Bipolar Spectrum Disorders. J. Soc. Clin. Psychol 26, 460-478. 10.1521/jscp.2007.26.4.460 [DOI] [Google Scholar]

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# data[].attributes.attachment_link.title
Traumatic events in Childhood and Adulthood in a Diverse-Ancestry sample and their role in Bipolar Disorder

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We examined the presence of adverse events in both childhood and adulthood and the prevalence of PTSD in individuals with Bipolar Disorder (BD). There were 191 adults diagnosed with BD Type I and 924 controls, of predominantly African Ancestry (AA). ...

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ประสบการณ์เชิงลบในวัยเด็กต่อสุขภาพจิตผู้หญิงโรคจิตเภทและไบโพลาร์

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ประสบการณ์เชิงลบในวัยเด็กต่อสุขภาพจิตผู้หญิงโรคจิตเภทและไบโพลาร์

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Background

Schizophrenia and bipolar disorder are severe mental disorders resulting in a high burden and immense costs for the society.Reference Kahn, Sommer, Murray, Meyer-Lindenberg, Weinberger and Cannon1 These disorders represent multifactorial complex lifelong challenges for the patients and their families, and may result in multiple severe episodes and additional comorbid symptoms throughout life, such as depression, anxiety and sleeping problems.Reference Kahn, Sommer, Murray, Meyer-Lindenberg, Weinberger and Cannon1 Adverse childhood experiences (ACEs) are well-established environmental risk factors for these disordersReference Stanton, Denietolis, Goodwin and Dvir2-Reference McKay, Cannon, Chambers, Conroy, Coughlan and Dodd7 with a recent meta-umbrella systematic review on modifiable risk factors showing that the largest global population attributable fraction (PAF) of schizophrenia spectrum disorders was linked to childhood adversities (PAF 38%),Reference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6 indicating a large preventive capacity. As detailed knowledge on specific ACEs represents important information to guide preventive efforts, it was of particular interest that childhood sexual abuse showed a 13% PAF for the development of depression.Reference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6 However, less is known about the extent to which specific ACEs are associated with schizophrenia and bipolar disorder. A recent study emphasised that specific ACEs may differentially predict specific mental disorders,Reference Salokangas, Schultze-Lutter, Schmidt, Pesonen, Luutonen and Patterson8 but most previous studies were often limited by information on only a few specific ACEs,Reference Varese, Smeets, Drukker, Lieverse, Lataster and Viechtbauer9 small heterogeneous cohorts or no representative reference group.Reference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6,Reference McKay, Cannon, Chambers, Conroy, Coughlan and Dodd7 This emphasises the need for large trans-diagnostic studies investigating the effect of a broad range of ACEs compared with a representative reference group.

Furthermore, among individuals with schizophrenia or bipolar disorder, ACEs correlate with a worse clinical course and greater severity of psychotic symptoms and suicidal ideation.Reference Prokopez, Vallejos, Farinola, Alberio, Caporusso and Cozzarin3,Reference Carbone, Pugliese, Bruni, Aloi, Calabrò and Jaén-Moreno4,Reference Leverich, McElroy, Suppes, Keck, Denicoff and Nolen10 Psychotic and manic symptoms represent the diagnostic criteria for schizophrenia and bipolar disorder, respectively, but symptoms of depression and anxiety including sleep disturbances have a large impact on everyday functioning. Resilience represents an important parameter to cope with symptoms of severe mental disorders as well as the challenges of everyday life. Yet, whether ACEs are associated with a negative impact on these features of general psychological functioning among individuals living with a schizophrenia or bipolar disorder diagnosis has not been sufficiently studied.

Aims

Using a large nationwide representative Icelandic sample of women from the general population, we therefore aimed to study the following research questions.

1. (a) Are specific types of ACEs differentially associated with schizophrenia or bipolar disorder than other ACEs?

2. (b) Among women with schizophrenia or bipolar disorder, is exposure to multiple ACEs associated with suboptimal psychological functioning, indicated by a higher symptom burden of depression, anxiety, sleep disturbances and lower coping ability?

Stress-And-Gene-Analysis cohort about Icelandic women

The Stress-And-Gene-Analysis (SAGA) cohort is a study of women aged 18-69 years residing in Iceland in 2018.Reference Valdimarsdóttir and Hauksdóttir11-Reference Yang, Þórðardóttir, Hauksdóttir, Aspelund, Jakobsdóttir and Halldorsdottir13 All Icelandic-speaking women with an address or telephone number (approximate n 104 197) were invited to participate in the study between March 2018 and July 2019. The participants of the SAGA cohort answered an extensive web-based questionnaire including questions on for example, demographic factors, psychological trauma history (in childhood and adulthood), psychological health and history of various diseases. As shown in a previous study about the SAGA cohort, the participants represent the general population of Icelandic women in terms of age, education, geographic location of residence and monthly wages.Reference Daníelsdóttir, Aspelund, Thordardottir, Fall, Fang and Tómasson12 A total of 29 367 women (mean age 44 years) with sufficient information on ACEs and childhood deprivation were included in the present study ( Fig. 1). All participants signed an informed consent. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving patients were approved by the National Bioethics Committee of Iceland (reference number: 17-238) and the Icelandic Data Protection Authority.

Information on schizophrenia and bipolar disorder diagnoses

Women reported whether they had ever been diagnosed by a healthcare professional (e.g. a psychologist or medical doctor) with either schizophrenia or bipolar disorder. A total of 108 women (0.4%) reported a diagnosis of schizophrenia and 479 (1.6%) of bipolar disorder, with 53 of these women reporting being diagnosed with both disorders, resulting in 534 women with schizophrenia or bipolar disorder. We had no information on the date of the diagnosis nor specific diagnostic details. Self-report information on severe mental disorders has been shown to represent valid information relevant for research purposes.Reference Supina and Patten14 For the overall analyses, we grouped women with schizophrenia or bipolar disorder together as having severe mental disorders. Women who did not report a schizophrenia or bipolar disorder diagnosis are referred to as the reference group.

Measurement of ACEs and childhood deprivation

ACEs were measured with a modified version of the ACE International Questionnaire (ACE-IQ) developed by the World Health Organization. The ACE-IQ consists of 39 items assessing the frequency of exposure to 13 types of ACEs before the age of 18 years: emotional neglect, physical neglect, emotional abuse, physical abuse (the latter four items were referring specifically to abuse/neglect by parents or a guardian), sexual abuse, domestic violence, living with a household member who misuses drugs and/or alcohol, living with a household member who is mentally ill or suicidal, incarceration of a household member, parental death or separation/divorce, being bullied, witnessing community violence and exposure to war/collective violence. Response options varied between items and could either be answered on a five-point scale (ranging from 0 (never) to 4 (always)), on a four-point scale (from 0 (never) to 3 (many times)) or answered dichotomously 0 (no) and 1 (yes). In the main analysis, the response option 'cannot/will not answer' was treated as no childhood adversity for that respective question. In the present study, we followed the recommended frequency scoring system, which takes into account the level of exposure for each ACE. We then generated three types of exposure variables:

1. (a) a continuous ACE-IQ total score ranging from 0 to 13, reflecting the number of ACEs the participants were exposed to;

2. (b) the total score categorised based on the distribution of the sample (0-2, 3-4 and ≥5 ACEs); and

3. (c) binary variables for each individual ACE type, coded as 0 (unexposed) and 1 (exposed).

Childhood deprivation was assessed with the question: 'Was your family's economic situation ever so bad that you suffered any deprivation as a consequence? For example, this could apply to deprivation of nutritious food and/or deprivation of warm clothes and appropriate footwear during the winter months', with response options ranging from 0 (never) to 3 (often). For analytical purposes, we grouped childhood deprivation into 'no' (never and rarely occurring) and 'yes' (sometimes and often), as has been done previously.Reference Daníelsdóttir, Aspelund, Thordardottir, Fall, Fang and Tómasson12

Measurements of psychological functioning

Questions on psychological functioning covered present-state mental symptoms and coping ability. Women reported their symptoms via the following measures, with higher scores indicating greater symptom severity: depressive symptoms were assessed with the nine-item Patient Health Questionnaire (PHQ-9) with a score ≥10 representing a well-established validated cut-off for a probable diagnosis of depression.Reference Kroenke, Spitzer and Williams16 Symptoms of anxiety were assessed with the Generalized Anxiety Disorder 7-item scale (GAD-7) with a score ≥10 representing a well-established validated cut-off for clinically relevant anxiety symptoms.Reference Spitzer, Kroenke, Williams and Löwe17 Sleep disturbances were assessed with the Pittsburgh Sleep Quality Index (PSQI), with 19 individual items generating seven component scores and with a PSQI ≥6 indicating clinically significant sleep disturbances.Reference Buysse, Reynolds, Monk, Berman and Kupfer18

We imputed data for women who responded to more than 75% of items on the PHQ-9, GAD-7 and PSQI. Mean scores were used to replace missing values in both PHQ-9 and GAD-7 questionnaires. For the PSQI questionnaire, we replaced missing values with single imputation using predictive mean matching (PMM, with default d = 5 and 20 iterations).

Perceived coping ability was assessed with the 10-item version of the Connor-Davidson Resilience scale (CD-RISC-10),Reference Campbell-Sills and Stein20 measuring individuals' perceptions of their ability to cope effectively with stress and adversity. The CD-RISC-10 scale has demonstrated good reliability and validity.Reference Campbell-Sills and Stein20 Items were summed to create a total score ranging from 0 to 40 with a higher score indicating higher levels of perceived coping ability.

Covariates

We included the following covariates: age at responding; civil status (divided into married or in a relationship and single or widowed); educational level categorised as primary education, secondary education (high school or vocational education), tertiary education A (BSc or equivalent) and tertiary education B (MSc or above); current personal monthly income (categorised into low (≤US$2527/month), moderate (US$2528 to US$5897/month), high (>US$5898); conversion rates according to Central Bank of Iceland, 17 October 2018); body mass index (BMI); and smoking status (never, previous and current).

Statistical analysis

We compared the study population's characteristics between women with and without severe mental disorders using the t-test for age (as continuous variables) and the chi ²-test for other variables and determined correlations between specific types of ACEs via rank-order correlations.

For the primary analyses, we grouped women with schizophrenia or bipolar disorder as one group, i.e. women with a severe mental disorder. We estimated prevalence ratios (PRs) including 95% CI of a continuous ACE-IQ total score via Poisson log-binomial regression models with the sandwich variance estimators.Reference Chen, Qian, Shi and Franklin21 We also compared women who endorsed different numbers of ACEs (3-4 and ≥5 ACEs) with women with 0-2 ACEs and women with childhood deprivation to women without childhood deprivation. We used the group of women with 0-2 ACEs as the comparison group because the majority of women (79.7% among women without a severe mental disorder v. 95.7% among women with a severe mental disorders) reported at least one ACE. We conducted a model adjusted for age and a model additionally adjusted for all other covariates.

Next, we estimated the associations of type-specific ACEs and severe mental disorders. To determine the independent associations of type-specific ACEs and severe mental disorders, we first ran type-specific analyses separately adjusted for all covariates, then re-ran the analysis additionally adjusted for other types of ACEs.Reference Yang, Thornorethardottir, Hauksdottir, Aspelund, Jakobsdottir and Halldorsdottir22

Finally, we performed analyses specifically among women with a severe mental disorder studying the association of ACEs (0-2, 3-4 and ≥5 ACEs) and childhood deprivation with psychological functioning (i.e. the severity of symptoms of depression, anxiety, sleep disturbances and resilience). We used both linear regression and Poisson log-binomial regression models to calculate the beta coefficient and PR adjusted for all covariates, respectively.

We performed several sensitivity and subgroup analyses. First, we re-ran all analysis separately for women with schizophrenia or bipolar disorder, respectively. Second, to assess the effect of missingness on our results, we re-ran our analysis restricted to participants without the 'cannot/will not answer' option on the ACE-IQ. Third, we replaced 'cannot/will not answer' with single imputation using PMM (with default d = 5 and 20 iterations). Fourth, as divorce is frequently occurring in Nordic societies and might not necessarily represent a severe ACE, we performed all analyses excluding this variable as an ACE. Fifth, as women with schizophrenia or bipolar disorder were younger and since recall bias might increase with age, we performed the analyses stratified by age.

Characteristics of the study population

Compared with the reference group, women reporting a diagnosis of severe mental disorder were younger, more often single/widowed, less educated, more often smokers and had lower income, higher BMI, greater severity of depressive, anxiety and sleeping symptoms, and had lower coping ability ( Table 1). Similar findings were noted for schizophrenia and bipolar disorder separately (Supplementary Table 1 available at https://doi.org/10.1192/bjp.2023.128).

Associations of ACEs and childhood deprivation with severe mental disorders

Compared with the reference group, women with a history of severe mental disorders had higher ACE scores (mean 4.57, s.d. = 2.82, v. mean 2.51, s.d. = 2.34), reported ACEs more frequently (48% reported ≥5 ACEs v. 19%) and experienced more childhood deprivation (27% v. 13%). ACEs and childhood deprivation were associated with higher PRs for having a severe mental disorder (Supplementary Table 2). Higher number of ACEs was associated with increasing PRs for having a severe mental disorder (fully adjusted PR = 1.23 per ACE; 95% CI 1.20-1.27) showing a dose-response association. Specifically, women who experienced 3-4 ACEs and ≥5 ACEs had a PR of 1.81 (95% CI 1.44-2.27) and 3.54 (95% CI 2.92-4.28), respectively (Supplementary Table 2). The result pattern was largely similar for schizophrenia or bipolar disorder separately (Supplementary Table 2), when stratifying for median age (Supplementary Table 3), when excluding parental divorce as an ACE (Supplementary Table 4), and when restricting this to 'complete cases' (Supplementary Table 5), although the 95% CIs were wide in the latter analyses, potentially owing to the small sample size. PMM analyses to assess the impact of missing data showed similar results (Supplementary Table 6).

The 13 specific types of ACEs were weakly to moderately correlated with each other (ranging from 0.05 to 0.51) with emotional abuse having the strongest correlation with other ACEs (Supplementary Fig. 1). Regarding the specific ACEs, all ACEs correlated with higher PRs for history of severe mental disorders when not including mutual adjustment for other ACEs, with the PRs differing between the specific ACEs ( Fig. 2). When including mutual adjustment for all other ACEs, the following ACEs were associated with higher PRs for having a severe mental disorder: emotional abuse (PR = 1.51, 95% CI = 1.21-1.88), sexual abuse (PR = 1.67, 95% CI = 1.38-2.03), mental illness of a household member (PR = 1.90, 95% CI = 1.56-2.31), emotional neglect (PR = 1.32, 95% CI = 1.07-1.64), bullying (PR = 1.43, 95% CI = 1.20-1.71) and collective violence (PR = 1.62, 95% CI = 1.11-2.36). Similar findings were noted for schizophrenia and bipolar disorder separately, whereas the association with emotional and sexual abuse was more pronounced in schizophrenia than in bipolar disorder (Supplementary Table 7).

Association between ACEs and current symptomatology

When specifically studying women with a severe mental disorder, we found that ACEs were associated with a greater current symptom burden of depression and anxiety including poorer sleeping quality, whereas childhood deprivation was associated with greater symptom burden of depression and anxiety ( Table 2). We observed similar patterns for specific types of ACEs (Supplementary Table 8). The severity of depression, anxiety and sleep disturbances increased (indicated by higher β-values) and coping ability decreased (indicated by a lower β-value) among women with a severe mental disorder and higher number of ACEs. Compared with women with 0-2 ACEs, women who reported ≥5 ACEs were more likely to have symptoms of anxiety (PR = 1.29, 95% CI 1.08-1.55), depression (PR = 1.27, 95% CI 1.18-1.36) and sleep disturbances (PR = 1.10, 95% CI 1.00-1.21, Supplementary Table 9).

Main findings

Based on the large and nationwide representative sample of Icelandic women, the present study comprehensively demonstrates a dose-response association between ACEs and severe mental disorders. Of 13 studied ACEs, we found seven to be associated with schizophrenia or bipolar disorder, the strongest associations were with mental illness of a household member and emotional and sexual abuse, but also emotional neglect, bullying and collective violence. Finally, and with important implications for clinical management, we found that among women with schizophrenia or bipolar disorder, the presence of ACEs was strongly associated with worse psychological functioning.

Comparison with findings from previous studies

Previous research on ACEs has primarily focused on ACEs as a risk factor for developing mental disorders and hence representing a potential target for prevention.Reference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6 The detailed assessment of specific ACEs in the present study indicates a pattern of some specific ACEs being more strongly associated with severe mental disorders than others, as well as potentially different roles of some specific ACEs for different mental disorders. In line with our findings, a recent umbrella reviewReference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6 found that childhood sexual abuse was particularly strongly correlated with risk of developing depression, although such a fine-grained evaluation on the potential role of other ACEs was not possible because of missing data on specific ACEs in individual mental disorders.Reference Prokopez, Vallejos, Farinola, Alberio, Caporusso and Cozzarin3,Reference Dragioti, Radua, Solmi, Arango, Oliver and Cortese6,Reference McKay, Cannon, Chambers, Conroy, Coughlan and Dodd7 Another recent study suggested potential differences between specific ACEs and the risk for specific mental disorders.Reference Salokangas, Schultze-Lutter, Schmidt, Pesonen, Luutonen and Patterson8 The present findings suggest that sexual but also emotional abuse is associated with a higher prevalence of both schizophrenia and bipolar disorder. Severe physical abuse has also been linked to subsequent risk of a mental disorder.Reference Fisher, Jones, Fearon, Craig, Dazzan and Morgan23 Although we cannot draw firm conclusions because of low statistical power in the analyses of specific types of ACEs, it seems that there exist important differences between specific ACEs and their associations with severe mental disorders that need to be considered in the context of prevention of these disorders. Furthermore, bullying and collective violence represent ACEs that can be targeted preventively, with bullying particularly representing a frequently occurring traumatic experience that seems highly relevant to target by preventive approaches. In addition, mental illness of a family member was considerably more frequent among women with schizophrenia but also bipolar disorder compared with the reference group. Although genetic factors may play a role, the negative impact of growing up with family members with severe mental disorders is well describedReference Gregersen, Søndergaard, Brandt, Ellersgaard, Rohd and Hjorthøj24 and the present results further emphasise the importance of supporting children of individuals with severe mental disorders with the aim of preventing the development of mental disorders.Reference Gregersen, Søndergaard, Brandt, Ellersgaard, Rohd and Hjorthøj24,Reference Uher, Cumby, MacKenzie, Morash-Conway, Glover and Aylott25

Importantly, our study adds new knowledge on the role of ACEs for general psychological functioning among individuals with severe mental disorders. Our findings indicate a strong negative impact on a large variety of mental health symptoms affecting the everyday functioning of these individuals, thus extending previous studies indicating that ACEs are associated with a worse clinical course.Reference Prokopez, Vallejos, Farinola, Alberio, Caporusso and Cozzarin3,Reference Carbone, Pugliese, Bruni, Aloi, Calabrò and Jaén-Moreno4,Reference Leverich, McElroy, Suppes, Keck, Denicoff and Nolen10 Hence, ACEs should represent an important treatment focus among individuals with schizophrenia or bipolar disorder, for example, via trauma-focused psychological interventions such as trauma-based psychotherapy, because of their detrimental effect on psychological functioning.

Potential explanations for the observed associations include psychological and biological models with these potentially being intercorrelated. The psychological stress of ACEs can persist into adulthood, thereby affecting adult mental health.Reference Heim, Newport, Heit, Graham, Wilcox and Bonsall26 Studies have shown that childhood adversities invoke stress-induced neurodevelopmental changes,Reference Heim, Newport, Heit, Graham, Wilcox and Bonsall26 such as hypothalamic-pituitary axis dysregulation and chronically elevated stress hormone levels causing structural brain changes, which can increase the risk for psychopathology. Furthermore, ACEs lead to aberrant DNA methylation and thus important epigenetic modifications, with these environmental imprints on the human epigenome persisting into adulthood.Reference Houtepen, Hardy, Maddock, Kuh, Anderson and Relton27 It is plausible that these mechanisms affect the individual during the entire life course and hence have a negative impact on psychological symptoms beyond representing a risk factor for developing a mental disorder.

Strengths and limitations

The strengths of the present study include the detailed assessment of a wide range of ACEs and childhood deprivation with detailed information on several important covariates, and the large and representative study population that was specifically designed to study the association between life course trauma and subsequent mental health in women.

Our study has to be interpreted in the light of potential limitations. First, our study is cross-sectional, thus it is not possible to draw any conclusions on the directionality of the observed associations. Second, women reported on lifetime diagnoses of schizophrenia or bipolar disorder and were not interviewed with a clinical diagnostic interview for participation in the present study. In addition, we had no information on the onset of symptoms or the date of the diagnoses. Nevertheless, schizophrenia and bipolar disorder represent severe mental disorders with good validity of self-reported diagnosesReference Supina and Patten14 and with these disorders having a lifelong impact on affected individuals. Third, we had no information on the diagnostic symptoms for schizophrenia and bipolar disorder (i.e. psychotic or manic) nor on the severity of the disorder or psychopharmacological treatment. Fourth, all variables represent self-reported measures, and although this is a well-established approach for assessing ACEs, we cannot exclude the possibility that diagnoses of severe mental disorders or current mental health symptoms affect retrospective reports of ACEs. Fifth, the present study only included women. Sixth, the relatively higher rate of bipolar disorder (1.6%) than schizophrenia (0.4%) may be because individuals with schizophrenia often experience a chronic course, which may have resulted in some women with schizophrenia not participating in this study.

Implications

The findings of the present study strengthen and extend previous findings on the detrimental impact of ACEs in women diagnosed with schizophrenia or bipolar disorder. Specific ACEs, including mental illness of a household member and sexual and psychological abuse, are strongly associated with these severe disorders, indicating the importance of considering specific ACEs in preventive approaches. Furthermore, ACEs and childhood deprivation were associated with worse psychological functioning among women with severe mental disorders. Our findings therefore strongly suggest that identifying a history of ACEs is important in the assessment and subsequent treatment of women with schizophrenia and bipolar disorder.

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Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study | The British Journal of Psychiatry | Cambridge Core

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Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study - Volume 224 Issue 1

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อัตราและปัจจัยเสี่ยงการทำร้ายตนเองในผู้ป่วยซึมเศร้า/ไบโพลาร์ในจีน

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อัตราและปัจจัยเสี่ยงการทำร้ายตนเองในผู้ป่วยซึมเศร้า/ไบโพลาร์ในจีน

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Prevalence and risk factors for non-suicidal self-injury among patients with depression or bipolar disorder in China - BMC Psychiatry

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Backgrounds Non-suicidal self-injury is a serious health problem among patients with depression or bipolar disorder. However, few studies within the Chinese context have investigated the prevalence of NSSI and its risk factors in above populations. The purpose of this study was to investigate the prevalence of non-suicidal self-injury and its risk factors in patients with depression or bipolar disorder in China. Methods The final sample comprised of 394 inpatients(Mage = 29.71; SDage = 11.95) with depression or bipolar disorder from two psychiatric hospitals in Beijing, China. A General Demographic Data Form, the Non-suicidal Self-injury Questionnaire(NSSI-Q), Impulsivity Item and the Adverse Childhood Experiences-International Questionnaire(ACE-IQ) were completed by all patients. Results Of the 394 patients examined, 245(62.2%) of this sample reported NSSI in past year. Of the 245 patients with NSSI, 135(55.1%) were diagnosed with depression and 110(44.9%) were diagnosed with bipolar disorder. The most common methods of NSSI for female was “pinching”(23.1%) and “scratching”(22.8%), while for male it was “hiting hard objects”(12.7%). By multivariate regression analysis, young age, unemployment, a higher monthly family income, single, impulsivity, long duration of illness and ACEs were risk factors for NSSI in patients with depression and bipolar disorder(P<0.05). Conclusions Our study points to the fact that there was an unfortunate message about the prevalence of NSSI among patients with depression or bipolar disorder in China. It is necessary not only to raise the awareness of NSSI in families and society, but also to formulate targeted assessment and intervention. Moreover, future research should not only focus on individuals being hospitalized, but should be representative of individuals treated at home or in the community because there are no national statistics on NSSI among such patients in China.

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ความเสี่ยงทางพันธุกรรมทำนายความเชื่อมโยงระหว่างประสบการณ์เชิงลบในวัยเด็กกับไบโพลาร์

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ความเสี่ยงทางพันธุกรรมทำนายความเชื่อมโยงระหว่างประสบการณ์เชิงลบในวัยเด็กกับไบโพลาร์

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Neurocognition กับประสบการณ์เชิงลบในวัยเด็กและประวัติครอบครัวที่มีความเจ็บป่วยทางจิตใจ

# data[].attributes.subject
Neurocognition กับประสบการณ์เชิงลบในวัยเด็กและประวัติครอบครัวที่มีความเจ็บป่วยทางจิตใจ