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Initially, this research project aimed to examine differences in mental health diagnoses in different socioeconomic areas. This was due to a small amount of research that suggested cases of Complex post-traumatic stress disorder (C-PTSD) could be misdiagnosed as Borderline personality disorder (BPD) (C-PTSD) (Pagura et al.,2010). The existing research suggested that people in lower socio-economic areas were more likely to be diagnosed with BPD (O’Donoghue et al., 2023).

This initial idea was discounted due to the limited relevant and up-to-date research available. The risk of unintentional bias is high due to personal lived experience. Lived experience can prove invaluable in qualitative studies, but only if there is no bias or triggers for the researcher or the participants, as this can become unethical (Sanjari et al.,2014).

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The second and decided research area became prevalent whilst reading about specific mental health issues. Synaptic pruning was becoming a theme in papers about the origins of mental illnesses and being suggested as a probable cause for autism (Weir, 2012;Silva,2018). Another theme that kept coming up was the immune system's role in synaptic pruning as an infant's brain develops (Bolton et al., 2022). The researcher then wanted to find out if stress in early life can lead to the immune system disrupting the synaptic processes and if this could lead to autistic-like behaviours in childhood and adolescence.

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Autism spectrum disorder is not categorised as a traditional medical disorder; instead, it is something a child is either born with or can develop in infancy. Although it is not classed as an illness as such, children with autism often need support to navigate their daily lives (NHS,2022).

Characteristics of autism include but are not limited to;

1.  Challenges with verbal and non-verbal communication.

2.  Difficulties reading social cues and challenges understanding or empathizing with others' thoughts and feelings.

3.  Becoming overwhelmed by bright lights, busy situations, and loud noises.

4.  Repetitive behaviours.

5. Anxiety about unfamiliar situations or people (NHS, 2022).

Autism is different for every child. Some children may struggle with repetitive behaviours, while others may struggle with communication difficulties (Da Conceicao, 2017). These varying aspects are why autism is considered a spectrum disorder, as it manifests in many different severities and symptoms (NHS Inform, 2024). There are no specific medications for autism, but some children take medicines that help with anxiety and hyperactivity. These include antipsychotic medication such as Risperidone or Clozapine. A study in 2012 showed that 56% of children with autism take these medicines (Arky, 2024). Whilst these can lessen the mentioned symptoms, they can come with unpleasant side effects such as fatigue, stomach upset, nausea and constipation. For a child already overwhelmed, these effects could add to their distress (NHS, 2021). A 2012 drug trial on mice showed promising results for Rapamycin. This medication reversed disrupted synaptic patterns and resolved most of the traits of autism. Still, this drug has only been proven to work when the symptoms have become problematic (Sato, 2012). This research aims to intervene before symptoms become problematic by providing early psychosocial interventions for children who have faced trauma or stress in infancy. (Kotajima-Murakai et al., 2019;Autism Speaks, 2023). Linking disrupted synaptic pruning with autistic traits would provide scope for further research into different medicines.

Currently, children with autism can face severe challenges in school. This can be attributed to schools' strict academic targets, insufficient funding, and inadequate training (Mahajan, 2022). This can lead to children facing barriers to education as they are expected to perform alongside neurotypical children. This can lead to a child becoming overwhelmed and exhibiting undesired behaviours such as shouting, becoming destructive, screaming, crying or even violent outbursts if sensory overload continues (Aheidel, 2023). Children can then face punishment, bullying from peers and stigma. If teachers had adequate autism training, this could be avoided (National Autistic Society, 2024). If more research and education were available on triggers and reactions, policies could be implemented to serve children with Special Educational Needs (SEN) better. Again, if a link between stress and disrupted synaptic patterns could be proven, early interventions could help a child before these undesired behaviours are exhibited.

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The question that arose before further reading was: Can abnormal synaptic pruning lead to autism in children and adolescents?

See Appendix 1 for a definition of Synaptic Pruning.

Many papers cite disrupted synaptic patterns as abnormal. However, the word abnormal was taken out of the question as it suggests something wrong with a person’s brain. This could be distressing for an affected person to read and could lead to the researcher inadvertently writing with an unintentional bias (Machi & McEvoy, 2016).

After further research, the question became, Can stress in infancy affect synaptic pruning and lead to autism in children and adolescents?

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Researchers must address ethical considerations when preparing an ethnographical study. These include social responsibility, informed consent, confidentiality and transparency (Iphofen & Tolich, 2018:Schuster, 1996).

Ethics in Research are guidelines a researcher must follow to prevent harm to anyone participating in the study or the researcher (Halej, 2017). For instance, participants must have all the information about the study, including any risks to them and their well-being. The researchers must obtain informed consent from all participants before proceeding (University of Oxford, 2021). Taking this into account, even though a biological theme is present in the study, it would be unethical to conduct an MRI scan on a child or an infant presenting with autistic traits as they cannot give informed consent (Mezinska et al., 2021).

Transparency is essential as informed consent cannot be obtained if a participant is unaware of certain parts of the study, for instance, if the person is being recorded without their consent or knowledge. Not only does this damage the relationship between the researcher and the participant, but it will make any evidence unreliable. Trust is crucial for both parties to enable honest responses to questions (Malicki et al., 2023). Confidentiality is crucial to protecting participants' data (Kaiser, 2009).

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Synaptic pruning is a biological process that occurs as a baby progresses to childhood, continues through to late adolescence, and stops when a person reaches their mid-twenties. Litchman (2020) describes the phenomenon as if a baby's brain can learn anything. As a child grows, their synapses begin to be selectively discarded. For instance, when an infant is learning to talk, the synapses for language begin to produce more, strengthening the connection and allowing the child to learn language quickly. However, the synapses not in use, for instance, synapses that may allow an infant to learn a foreign language, begin to be marked for destruction and are consequently eliminated (Sakai, 2020).

Many papers cite that the disruption of the synaptic pruning process is abnormal (Bolton et al.,2022;Sakai, 2020;University of Cambridge, 2023;Weir 2012).

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Bowlby Attachment Theory

John Bowlby (1907-1990) proposed a theory in 1958 that maternal deprivation can affect how a child attaches themselves to those around them. Bowlby (1958) proposed that an infant needs a maternal figure through the ages of 6-30 months. Failure to establish this bond with a mother or the disruption of an existing attachment could result in severe and irreversible damage to a child's emotional, social and cognitive development. A child with an insecure attachment type can exhibit traits consistent with autism, such as social difficulties, avoiding contact with people and challenges controlling their emotions (Tizard, 2009). Bowlby's theory emphasises the significance of a secure and loving environment and its effect on a child's development. However, this theory overlooks the role of other caregivers and environmental factors. Bowlby (1958) places the blame for developmental difficulties entirely on the mother, discounting any reasons for maternal absence or neglect (Cardwell & Flanagan, 2015).

This theory intersects with disrupted synaptic pruning as it identifies the same critical development period; synaptic pruning is most prevalent between 18 months and 2 years. There is also a similarity in that both concepts state that stressful events can affect development, whether that is maternal deprivation or trauma at birth. Synaptic pruning focuses on the biological development of the brain with the added stresses of adequate caregiving, maternal infections or stresses (Sakai, 2020).

Analyzing Bowlby's theory of maternal deprivation and synaptic pruning provides valuable insights into the effects of social experiences and neurobiological processes on child development. While his theory has deepened the understanding of attachments, caregiving, and their impact on growth, new and ongoing research is needed to address the interconnected social and biological processes of early childhood experiences and their implications for health and well-being (Barnes et al., 2018).

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Quantitative Research

This type of research is used to examine amounts; for instance, a method here would be a survey sent out to a whole community. The results would then be analysed in potentially large generalised quantities (St. Petersburg College, 2022).

Quantitative research could be potentially helpful in this research project as a small sample is needed, but this could be achieved by sending out surveys or questionnaires to narrow down people diagnosed with autism in certain areas. This numerical data could then be used to run focus groups with a small sample size (Watson, 2015).

This methodology, whilst sometimes helpful, could also prove difficult as it relies on people being honest. It also can discount diversity, ethical issues, and bias. Some of the questions that need to be answered could be triggering or too intrusive for some people, and with quantitative research, these ethical issues may be missed (Watson, 2015).

Qualitative Research

Unlike quantitative research, qualitative research is used on a larger sample. This aims to grasp a deep and rich understanding of participants' experiences within their everyday contexts (Denscombe, 2017). Qualitative researchers can gather data by immersing themselves in the lived experiences of individuals. They achieve this by observing participants as they go about their everyday lives. By doing this, they gain invaluable insights, which could not be achieved with quantitative research as people can act differently if they feel pressured or fill out a questionnaire in a rush. This could make the data inaccurate (UK Research and Innovation, 2024). In this project, an Ethnographic study would be most beneficial. Ethnographical studies are a type of qualitative research. This methodology uses unstructured interviews, focus groups, observations, and journal-keeping. By doing this type of study, researchers can also observe participants' mental well-being and tailor questions not to upset or trigger a person, they can also respond quickly and effectively to any ethical issues that may arise (Office for Health Improvement and Disparities, 2020;Fomby & Sastray, 2019). A consent letter must be filled out to ensure participants know this study may be triggering and upsetting. This letter will include numbers of organisations to call if they need any help, and also, they will have the right to pull out at any time in the study.

Mixed Methods

This consists of a researcher using qualitative and quantitative methods to gather and analyse data. This methodology could answer questions that qualitative and quantitative methods could not answer solely. For example, for a question that asks for an extensive study of children with autism, quantitative research could be used here as an initial questionnaire. Then, qualitative research could be used to conduct focus groups. The process of mixing two different methods could prove too complex and too time-consuming. It can, however, help narrow down large samples to a more focused group ( Shorten & Smith, 2017).

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Sample consent letter/form

Dear Participant,

I am writing to invite you to participate in a research study on synaptic pruning and autism. This study aims to ascertain if there are any links between premature or late synaptic pruning and autism.

If you choose to go ahead with this project, please be aware that some of the data collection, such as interviews and questionnaires, may be sensitive. If at any time you feel distressed, please let the person carrying out the interview know, and the interview will be stopped, and appropriate support will be arranged for you. Please see the end of this letter for agencies that can help with mental well-being.

The study will run for approximately 12 months. Participation in this study is entirely voluntary, and you can withdraw your consent at any time during the study. If you choose to withdraw from this study, any information collected from you will be destroyed.

Any information acquired from you will be kept strictly confidential, and any personal information, such as names, will be replaced with pseudonyms to ensure absolute confidentiality.

If you have any concerns about this study, please do not hesitate to contact Dr Fiona George at 07689942002 or Fiona.George@gmail.com. Mental health support is available at Hull & East Yorkshire MIND at 01482 489766. If you do not feel comfortable reaching out yourself, please let the researcher know, and support will be put in place for you.

By signing this letter, you confirm that you understand the information outlined in this letter and consent to participate in this study voluntarily.

Signature:

Printed Name:

Date:

(Fraizer, 2023;Curran et al., 2018).

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(Denscombe, 2017;Iphofhen, n.d.;Calman et al., 2013).

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This research investigates the relationship between early life stress, synaptic pruning processes and the development of autistic traits in childhood. There will be three main objectives these are as follows;

1.  To explore the relationship between early life stresses and altered patterns of synaptic pruning. These stresses can include but are not limited to maternal infections in pregnancy, outside influences such as adverse childhood events (ACEs) and factors such as the broader determinants of health, for example, low socioeconomic status or health problems in infancy and altered patterns of synaptic pruning (Hoover & Kaufman, 2018).

2.  To ascertain if early life stresses can disrupt the immune system and, if so, can the immune system alter the synapse patterns (Krystal et al., 2017).

3.  To find out if it is possible to predict autistic traits and the severity in children who have been exposed to trauma in early life and if this can be proved, find a way to help those children by working on strengthening synaptic pathways that have been disrupted (Halperin & Healey, 2011).

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By conducting a 12-month study, the researcher can observe participants throughout the weekly sessions. These observations will be written up in a journal. Numbers will be used in place of names to identify participants in these reports to protect their confidentiality. The people will be informed that observations and subsequent journalling will be carried out throughout the study. There will always be an option to withdraw from the research, which will be communicated to the participants multiple times (Calman et al., 2013).

Semi-structured interviews will collect data by inviting people to share their experiences. The questions will be open-ended so the person can choose how much information they want to give. This can help build rapport and trust with the researchers. Again, the questionnaires used in these interviews will be numbered instead of named. This data will be password-protected in an electronic spreadsheet to ensure confidentiality (Office for Health Improvement and Disparities, 2020:Kaiser, 2009). Focus groups will also be used. These groups will take place weekly, and teachers, children, and caregivers will be invited to these sessions to comprehensively understand each individual's different challenges (O.Nyumba et al., 2018). These group sessions will be voluntary, and a moderator will attend to guide the conversations to minimise the risks of distress or heated discussion (Pickering & Watts, 2016).

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Once all the data is collected, researchers have numerous software programs they can use to help them clean and narrow down their data, allowing them to find correlations and patterns relevant to their area of research. One such software is Statistical Package for the Social Sciences (SPSS) (University of York, 2024). This software is used in quantitative studies. SPSS allows users to input data, and the software will clean up any errors, such as duplicated entries, or any anomalies, such as incomplete entries. This software will also create statistics and patterns from large numbers, allowing the researcher to read their findings easily (Garth, 2008). However, this software can be challenging to navigate for new users, and training may be needed, adding extra costs. SPSS is inappropriate for the study here as it requires and works with large amounts of numerical data, and the ethnographical research is much smaller. It also does not allow for visual or recorded data (Masuadi, 2021).

A helpful software package for Qualitative data is NVivo. This software allows the input of different data formats, such as video files, interviews, audio files, and spreadsheets (University of Cambridge, 2024). This is useful as qualitative studies use several different tools to collect data. Once the data is put into this software, it can be used to identify themes by coding. This means highlighting words that appear throughout the data set. This helps the researcher identify patterns and themes for thematic analysis (University of Surrey, 2023). This software is also helpful for mixed methods as it allows several different data formats, such as questionnaires and interviews, to be put in and analysed alongside data tools such as focus groups (Dhakal, 2022). Although this could be useful here, Nvivo is a very complex software, and a user needs a good level of familiarity with it to use it effectively. This can be highly time-consuming. It is also costly, with an annual licence costing £986.56 (Capterra, 2024).

Manual thematic analysis is the preferred method for this study, given the costs and training needed to use NVivo. It also allows the researcher to adapt their approach to the unique characteristics of each set of data (Naeem et al., 2023). To analyse evidence of a link between disrupted synaptic pruning and autistic traits, themes must be identified and analysed to identify patterns and correlations with adverse life events (Braun & Clarke, 2014). Once all the data is collected, the researcher must familiarise themselves with it by reading, listening, and using visual aids numerous times. This can assist with spotting errors, duplications, or incomplete data. This familiarity can also help the user notice certain consistently used words. For instance, words such as stress, ACEs, Autism, age, and immune system are themes that will be looked for (Coates et al., 2021). Once this initial analysis has been conducted, it would be helpful to make a data matrix to assist in noticing patterns, similarities, and themes. Once all the data has been coded and reviewed, the themes will be applied back to the research question (Nowell et al., 2017). Finally, the findings will be written up. For instance, a narrative of each theme will be written and linked back to the data. These findings will be added to existing literature, highlighting gaps and the need for further research (Damyanov, 2023).

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Three primary research methodologies are used in social science research: Quantitative, Qualitative, and Mixed Methods (See Appendix 4 for detailed descriptions).

For this project, an ethnographic study, a type of qualitative research, will be conducted. Ethnographical studies allow researchers to immerse themselves in participants' everyday lives (Allen, 2017). This approach aims to gain a comprehensive understanding of the daily functioning of parents and children with autistic traits, including the discrimination and stigma they may face (Turnock et al., 2022).

While quantitative research could provide valuable insights, a smaller sample will be studied here. In quantitative studies, the impersonal and structured questions may inhibit honesty among the participants; this could affect the credibility of a quantitative approach (Weller et al., 2018) By conducting face-to-face interviews, the researcher can ask semi-structured questions, which allows for a person to respond with as much or as little information as they are comfortable with. This could help build trust and rapport with the interviewer.

Participants will be selected by gathering data from primary schools in the North Yorkshire region (See Appendix 6 for an initial timeline of this study). Families identified with children who have a diagnosis or are awaiting an assessment for autism will receive a letter explaining the research and inviting them to take part. The school will distribute the letters to protect the addresses and confidentiality of the potential participants.

The researchers ' contact details will be provided on the invites for people to enquire. This initial phase will be carried out over 2 months to give people ample time to determine whether or not they wish to participate (UK Research and Innovation, 2021). After this, the participants who want to participate will be contacted by providing their contact details or through the school, and they will be invited to an initial focus group (See Appendix 5 for a sample letter). Provisions for childcare will made available for children with autistic traits. Understanding that routine is often essential, appointments will be conducted consistently to minimize distress (NHS, 2022).

The initial focus groups aim to recognise any links between ACEs, trauma, or problems in pregnancy with autistic traits in the children. Given the sensitivity of these discussions, questions will be worded emphatically, and counselling will be available for any participants who may become distressed (Iphofen, n.d.).

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Can stress in infancy affect synaptic pruning and lead to Autistic traits in childhood and adolescence?

This literature review delves into potential associations between early life stress, disrupted synaptic pruning, and the emergence of autistic traits during childhood and adolescence. Initial findings suggest correlations between delayed or ineffective synaptic pruning and autistic traits prevalent throughout childhood and adolescence (Sakai, 2020; Tang et al.,2014; Fluery & Kemper, 2022). Moreover, this review aims to highlight gaps in existing literature, providing opportunities for further research and changes in current policies and procedures. Updating outdated policies and procedures could empower children and their caregivers while informing teachers and care practitioners on the best ways to approach and help children with SEN (Fluery & Kemper, 2022).

Several scholarly articles will be scrutinised using a data matrix (See Appendix 2) to evaluate research methodologies, derive themes, and identify existing research gaps. This evaluation will include four quantitative studies, three qualitative studies, and two mixed methods studies, ensuring a balanced analysis of these studies (Snyder, 2019).

This review explores potential causes of disrupted synaptic pruning, indicating that emerging research points to early life stress, maternal infections, and trauma at birth or infancy as potential causes (Weir, 2012;Silva, 2018;Bolton et al., 2022). This points towards biological and environmental factors in the development of autism (Bolton et al., 2022).

Historically, and even presently, children with undiagnosed or diagnosed autism are often labelled as naughty, attention-seeking and uncontrollable. This labelling is more prevalent in lower socioeconomic areas with limited access to diagnostic resources (Adams, 2023;Roman-Urrestarazu et al., 2021). These disparities highlight an urgent need to address health inequalities and enhance diagnostic measures in these areas to combat misdiagnosis and stigma. Back In the 1960s, children with these types of behaviours, such as trouble with social difficulties and problems with communication, were attributed to the child having an insecure attachment type (Bowlby, 1969). This theory places unwarranted blame on the mother (See Appendix 3 for detailed analysis). If the proposed links can be proven, this theory could be proven to be outdated. Unfortunately, this way of thinking is still prevalent today, with many people blaming the parents, especially mothers, for their children's autistic behaviours (Hollingsworth et al., 2023).

Approximately 70% of children with SEN attend mainstream schools, which can add even more adversity (Autism Education Trust, 2023). Children with autism can suffer from problems with communication, lack of social skills, and repetitive behaviours, with some relying on strict routines to avoid becoming overwhelmed (Center for Disease Control and Prevention, 2023;NHS, 2023). When a child does become overwhelmed, they can exhibit unwanted behaviours such as screaming, shouting, and crying. They may suffer violent outbursts, leading to punishments by untrained staff members, bullying from peers and further social withdrawal. Other parents can also stigmatise the child’s family if they are perceived as unable to control their child (Selman et al., 2017;Health Research Authority, 2023).

In the United Kingdom (UK), schools are expected to provide the first £6,000 out of their budget per child with SEN (York Sendiass, 2023). With 166,041 autistic children in schools around the UK, this amounts to just under £1 million schools must find annually (Autism Education Trust, 2023;Selman et al., 2017;Health Research Authority, 2023). Establishing a potential link between disrupted synaptic pruning and autism development provides an opportunity to optimize early psychosocial interventions. This could lead to an opportunity to explore pharmaceutical treatments that work on the synapses to help alleviate a child's symptoms (WHO, 2023;Autism Speaks, 2023). There has been evidence that the medicine Rapamycin reverses ineffective synaptic pruning and eliminates the social difficulties of autism in adult mice; the repetitive behaviours, however, persisted (Autism Speaks, 2023). Although mice share 92% of DNA with humans and share some identical genes, their genes and cells function in different ways which is why 90% of drugs tested and proven in animals do not make it to human trials (Zimmerman & Zucker, 2020;Magee, 2023).

In 2014, a study was published that aimed to prove that children with an autism diagnosis had far more synapses than a neurotypical child (Tang et al., 2014:Columbia University, 2014). This was a relatively small study given the limited number of specimens, but due to the way results were derived using numbers, measurements, and formulas, this was carried out using a quantitative methodology. No wider determinants were considered, such as early life adversity, socioeconomic status, and experiences (Denscombe, 2017). The study also took place on post-mortem brains. Whilst studies on post-mortem brains can be beneficial in recognising factors such as synaptic patterns, it is crucial to recognise that post-mortem tissue is not the same as living tissues, and these samples have often been subject to treatments with chemicals to freeze and preserve them, which could affect the validity (Stan et al., 2006).

Other papers use a qualitative approach through observational methods. Unlike quantitative studies, these methods examine socioeconomic status, genetics, immune system issues and life experiences. They seek to gain a deep understanding of factors that can lead to excess synapses. They do this by carrying out ethnographical studies, which involve a researcher immersing themselves into a person's life to seek out a well-rounded and comprehensive understanding of specific themes that arise within these studies. These include the immune system, early life adversity, and genetic predispositions (Aylward et al., 2021:Autism Speaks, 2023:Weir, 2012). Qualitative research does have a few drawbacks as it requires the researcher to be involved directly in a person's life. This may cause the researcher to develop a bias toward the people in the study. Because this methodology works by developing trust and rapport with people, ethical guidelines must be strictly adhered to avoid psychological harm to people in the study (Khankeh et al., 2015).

In conclusion, by examining different perspectives and evidence, this review aims to advance the understanding of the relationship between the themes mentioned (age, trauma, immune system, and synaptic pruning) and altered patterns of synaptic pruning. The knowledge gained can inform early interventions that empower children and their families/caregivers. Gaps in literature, such as the prevalence of misdiagnosis in deprived areas, warrant further research to ensure these children do not fall through the gaps.

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This research has highlighted the significant challenges faced by children with autism, especially in schools where education and understanding may be lacking. This highlights a need for early interventions to be put into place to empower these children and their families. These interventions could also help reduce the stigma that comes with an autism diagnosis (Lodder et al., 2020). Possible pharmacological solutions are also explored to help these children's social difficulties. However, studies have only been conducted on mice, and 90 per cent of the time, these studies bear no relevance to humans (Bracken, 2009). Further research is needed in this area, but human clinical trials can take 10-15 years. This can be considered unethical as there is always a risk of adverse side effects in clinical trials, and only adults can participate (Cancer Research UK, 2022). This study also advocates for improvements in existing policies and practices to meet the needs of children with SENs better. Although no studies have been carried out on living brain tissue, post-mortem studies have found excessive synapses in autistic brains (Fetit et al., 2021). By looking at possible external causes of this, the literature pointed to trauma in birth, infancy, or stress in early childhood. Due to this, research into how many children with autistic traits had faced early life stress or trauma was suggested. Stress and trauma can disrupt the immune system, which is primarily responsible for synaptic pruning (Morimoto & Nakajima, 2019). Taking this into account, procedures could be initiated to attempt to reverse or lessen the effects of the disrupted patterns. These measures include sensory experiences, gentle physical exercise, and additional help with factors such as speech and communication difficulties and problems with writing, reading, or solving simple maths problems (Tuan et al., 2021). By educating academics and educational institutions about the link between synaptic pruning and autism, experiences at school for the affected children could be a lot better. Children with these traits can be labelled as naughty, disruptive and unable to learn in line with academic targets. They are often put in classes with lower academic targets with children with similar needs, which can cause sensory meltdowns, whereas an individual approach to help a child would be more beneficial. This way, they get tailored assistance and will not suffer the labelling and stigma (Goodall, 2018).

Recommendations

Better education and training for teachers/carers/parents to recognise signs of stress, developmental difficulties and early interventions for children who have suffered early life stressors.

Further research into this subject should be encouraged as the more research, the more funding will be available for studies and to inform training and education on this subject.

Changes to policies at government levels to improve support and inclusive educational practices for autistic children and their families. This could include making more funds available for schools, training, and education.

Education for the wider public on the potential link between early life stress, disrupted synaptic pruning and the manifestation of autistic traits.

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