Exploring the relationship between childhood trauma and psychosis; a review of the literature

Mark Cecchetti

Teen Trauma Shadow image

Abstract

Although the exact physiological processes that result in the experience of psychosis remain unclear, the literature consistently demonstrates that a combination of neurobiological and environmental factors contribute to the development of the illness. One such environmental factor that represents a significant risk factor for the development of symptoms across the extended psychosis phenotype is exposure to traumatic experiences in childhood. This paper explores the wealth of epidemiological research to support this position. The nature of this relationship is complex, with genetics, brain physiology and various environmental factors including childhood trauma each playing a role in the development of psychosis. Psychosis treatment outcomes have also been shown to be poorer in individuals reporting a history of childhood abuse. However, several methodological limitations have been identified in the body of literature, including issues with definition and measurement that need to be addressed in order to fully establish the nature of the relationship between childhood trauma and psychosis. Though a relationship between the two exists, childhood adversities are neither necessary nor sufficient to trigger the onset of psychosis. Key clinical implications arising from the research are also discussed.

Introduction

Although the exact physiological processes that result in the experience of psychosis remain unclear, the literature consistently reports that a combination of neurobiological and environmental factors contribute to the development of the illness1. One such environmental factor frequently highlighted in the body of research is exposure to childhood trauma. The term ‘trauma’ refers to a large variety of negative experiences including emotional, physical or sexual abuse and neglect. There is much epidemiological research to support the position that exposure to traumatic experiences in childhood represents a significant risk factor for the development of psychotic disorders and symptoms across the extended psychosis phenotype2,3,4. Though there is a general consensus that a link does exist between childhood trauma and psychosis, there is some debate surrounding the significance of this relationship as well as the types of trauma associated with an increased risk of developing psychotic symptoms. In addition, much of the research in this area is cross-sectional in nature, with the majority of studies relying on self-reported retrospective accounts of traumatic experiences. There are also numerous inconsistencies in the research regarding other biological and environmental factors that may mediate this relationship. This paper aims to review the literature exploring the link between childhood trauma and psychosis, and comment on the clinical implications of this relationship. Due to the paucity of research specifying the onset age of psychosis as being before 18 years5, this paper will focus primarily on early onset psychosis and psychosis being experienced in early adulthood.

Trauma

Childhood trauma can be broadly defined as the harm, potential for, or threat of harm to a child often resulting from the commission of abuse or the omission of sufficient care6. This definition captures a wide range of adverse experiences including emotional, physical or sexual abuse, emotional and physical neglect, bullying and parental separation or loss7. In a large-scale study of adverse childhood experiences involving 9,508 participants, 50% of respondents reported having been exposed to at least one adverse experience before the age of 188. This study also provided support for the hypothesis that childhood adversities tend not to occur in isolation, with 25% of respondents being exposed to 2 or more categories of abuse. Interestingly, it has been noted that accurate prevalence rates of childhood trauma are difficult to obtain due to the systemic under-reporting of experiences9, suggesting that the true prevalence rate may be even higher than the current estimates. This high prevalence rate of abuse and maltreatment among children poses significant challenges for survivors and for health care providers10. Exposure to abuse during childhood serves as a significant risk factor for maladjustment and the development of psychopathology later in life11. Negative childhood experiences have also been associated with impairment in a range of functional domains12, as well as with the development of many specific psychological disorders including anxiety, personality and dissociative disorders13.
The significant body of research that has emerged over the past few decades has greatly enhanced our understanding of the relationships between childhood adversity and subsequent psychological difficulties. Historically, trauma research has tended to focus on physical and sexual abuse, largely overlooking other types of adversities5,14. More recent research has expanded the conceptualisation of trauma to increasingly include emotional abuse15, neglect16, parental loss, separation or disharmony17 and bullying18. Understanding the breath and complexity of the traumatising experiences children can be subjected to allows researchers to more accurately investigate the extent of the relationship between childhood trauma and psychological difficulties later in life.

Psychosis
 

The DSM 519 characterizes disorders as psychotic or on the schizophrenia spectrum if they involve auditory or visual hallucinations, delusions, disorganized thinking or a variety of negative symptoms such as apathy or lack of emotion. The term psychosis is often used to describe the range of experiences people may have that include any combination of these symptoms in varying degrees of severity20. Psychotic experiences in the body of research are often defined broadly and are discussed using terminology such as schizophrenia, schizoaffective disorder, first episode psychosis, and delusional disorder2.
There is also a general consensus among researchers that the psychosis phenotype can be expressed at levels significantly below its clinical manifestation, commonly referred to as sub-threshold psychotic experiences, psychosis proneness, schizotypy or persons at risk of psychosis21,22,23. This concept of a psychosis continuum implies that the same symptoms observed in patients with psychotic disorders can also be measured in non-clinical populations. This is an important development in understanding psychosis and exploring its relationship with childhood trauma. Experiencing symptoms of psychosis such as delusions and hallucinations may only be considered a disorder depending on symptom characteristics such as frequency, intensity or intrusiveness, and personal characteristics such as one’s use of coping strategies and distress tolerance23. Therefore, even though the prevalence of the clinical disorder may be relatively low, the prevalence of the symptoms among the general population at sub-threshold levels may be much higher.

A lack of clarity has been highlighted in the research base concerning the terminology and definition of both psychosis and childhood trauma. Inconsistencies in the literature regarding what experiences constitute a trauma and what severity level of psychotic symptoms constitutes psychosis can lead to discrepancies between research studies and issues with replicability24.

Exploring the Association between Childhood Trauma and Psychosis

The evidence demonstrating an association between childhood trauma and psychosis has been consistent.  In one meta-analysis, 87% of individuals identified as being at ultra-high risk of transitioning to psychosis reported having prior exposure to childhood trauma25. Another meta-analysis concluded that individuals experiencing psychosis were significantly more likely to have been exposed to a wide range of childhood traumas including sexual, physical and emotional abuse or neglect, than healthy controls4. Furthermore, a recent meta-analysis involving 23,668 participants from 10 studies revealed that victims of childhood bullying were over twice as likely to develop psychotic symptoms later in life26. In addition, exposure to cumulative adversities have been shown to increase the risk for psychotic disorders significantly more than those exposed to a singular type of trauma27,28.

Relatively little research has been conducted exploring the relationship between childhood trauma and psychotic symptoms being experienced before the age of 18. One longitudinal twin study involving 2,232 participants found that children who had experienced severe maltreatment were more likely to report psychotic symptoms before the age of 12 than children who did not experience such maltreatment29. The higher risk of experiencing psychotic symptoms was observed regardless of whether the traumatic experiences occurred early in life or in later childhood. In addition, the increased risk associated with childhood trauma remained significant when controlling for other potential mediating biological and environmental factors such as gender, socioeconomic deprivation, and IQ. Similarly, in a study following 2,230 adolescents from age 10 to 16 years, a history of childhood trauma was found to be associated with subclinical experiences of psychotic symptoms30. This evidence suggests that a similar association is observed between childhood trauma and the development of psychosis, regardless of whether the onset of the disorder occurs in childhood, early adulthood or later in life.

However, several limitations the have been identified in the body of literature exploring the relationship between childhood trauma and psychosis. Loewy et al.24 highlight the controversial issue that many clinical cohort studies rely on the retrospective self-reporting of childhood trauma, obtained after the onset of psychotic experiences. They suggest that self-report data from individuals experiencing psychotic symptoms may be unreliable. Conversely, research conducted by Fisher et al.31 demonstrated that self-reports are stable over time and unaffected by current psychopathological symptoms. Hardt and Rutter32 attempted to address this limitation by evaluating the validity of self-report data, comparing disclosures with independent court or clinical records and collecting the retrospective reports of multiple siblings. The authors found that the self-reports of childhood trauma by individuals experiencing psychosis are under, rather than over-reported.

Research has demonstrated that specific kinds of childhood adversities may lead to specific psychotic symptoms. Exposure to childhood physical and sexual abuse have been found to be strong predictors of positive psychotic symptoms33. Childhood trauma has been proposed as a causal factor for certain positive symptoms of psychosis including voice hearing and command hallucinations34. Most consistently, research has indicated that a history of childhood adversities may increase the severity of positive symptoms of psychosis, specifically auditory hallucinations and delusions35. One study involving 184 participants diagnosed with a variety of schizophrenia spectrum disorders concluded that childhood adversities may influence the severity of delusions and hallucinations in a dose-response relationship36. Additionally, in a study involving in depth interviews with 61 severely maltreated children, it was found that the content of their hallucinations strongly resembled the nature of the trauma they were subjected to37. A recent systematic review and meta-analysis supported this position, concluding that traumas in childhood may lead to an increased severity of hallucinations and delusions within psychotic disorders38. Similarly, experiences of childhood neglect have been associated with paranoia and negative symptoms39. A study involving 2,765 patients with psychosis provided further support for this position revealing that neglect was significantly more associated with negative symptoms of psychosis40.

The often limited evaluation of the nature and degree of childhood trauma is a methodological issue consistently identified in the body of literature5. Many studies rely on the endorsement of a single question to consider a particular category of trauma as present or not. Important aspects of childhood trauma that may mediate the relationship with psychotic disorders, such as age of exposure and relationship to the perpetrator, are also not addressed in many studies31.

Though there is significant evidence in the body of literature demonstrating an association between childhood trauma and psychosis, there is also research reporting conflicting findings that do not fully support this association. In a 4 year longitudinal study involving 105 patients at ultra high risk of developing psychosis, no evidence was found to suggest that childhood adversity was associated with transition to psychosis41. Similarly, a study involving 764 individuals identified as being at clinically high risk of developing psychosis concluded that childhood trauma was not a reliable predictor of later transition to psychosis42. A more recent meta-analysis involving patients at ultra-high risk of psychosis, found that only sexual abuse and not other types of childhood trauma was significantly associated with transition to psychosis43. This suggests that exposure to childhood trauma alone may not be sufficient to bring about a higher transfer to psychosis rate among ultra-high risk individuals. The research indicates that childhood trauma may interact with other genetic and environmental risk factors to result in an increased risk of developing a psychotic disorder.

Biological models linking childhood trauma and psychosis

It has long been hypothesized that there is likely to be a biological influence on the development of psychotic disorders20. Twin studies from around the globe have played a vital role in establishing a genetic contribution to the aetiology of schizophrenia and psychosis spectrum disorders44,45. The biopsychosocial model of psychosis is a model that looks at the interplay between biology, psychology, and socio-environmental factors in the development of psychosis and schizophrenia spectrum disorders. Research into the aetiology of psychotic disorders consistently demonstrates a complex interaction between genetic and environmental factors46. The evidence indicates that stressful life events may influence critical periods of brain development, triggering the onset of psychosis later in life47.

The traumagenic neurodevelopmental model of psychosis3 emerged as an attempt to explain this process, highlighting the impact trauma can have on the developing brain. Research has demonstrated increased stress sensitivity among individuals experiencing psychotic symptoms48. The traumagenic neurodevelopmental model attributes this observation to trauma-induced neurodevelopmental changes during crucial periods of brain development in childhood.
Psychosocial stress, in particular childhood trauma, is hypothesized to interact with one’s predisposing genetic vulnerability or in certain cases alter gene expression via epigenetic mechanisms to contribute to the development and maintenance of psychotic disorders49. Interestingly, one review found that the role epigenetic dysregulation plays in the onset and development of psychosis and schizophrenia-spectrum disorders is becoming increasingly recognized50. Several biological mechanisms have been proposed attempting to explain this interaction between psychosocial stress, trauma and the experience of psychosis:

The Hypothalamic-Pituitary-Adrenal (HPA) axis response:

The HPA axis is a neuroendocrine unit comprising of the hypothalamus, pituitary gland and the adrenal glands. It plays a vital role in basal homeostasis and in regulating the body’s stress response processes. A main function of the axis is the production and secretion of cortisol, a hormone released during times of stress increasing heart rate, blood pressure, respiration and blood glucose51. Substantial evidence indicates that individuals diagnosed with schizophrenia spectrum disorders or experiencing psychotic symptoms exhibit HPA axis dysregulation. It has been reported that individuals experiencing psychosis are characterized by elevated morning cortisol levels52, higher diurnal cortisol levels53 and reduced cortisol response to stress54.

The experience of trauma during childhood results in the activation of the stress response and HPA axis, with prolonged or repeated trauma resulting in sustained over-activation of the system. The traumagenic neurodevelopmental modelhypothesizes that long-term exposure to such stressors and activation of the HPA axis may result in elevated levels of glucocorticoids such as cortisol. This disruption to the normal functioning of the HPA system has been linked to the increased likelihood of developing psychosis and schizophrenia spectrum disorders.

The experience of psychosis has also been demonstrated to accompany other physiological brain abnormalities. A meta-analysis revealed higher pituitary gland volumes in individuals at risk of psychosis and first episode psychosis patients when compared with healthy controls at trend level significance55. In addition, research has demonstrated that a history of childhood trauma may be associated with lower amygdala and hippocampus volumes in patients experiencing psychotic symptoms56. In one study involving 60 patients with a psychotic disorder, sexual abuse, but not other types of childhood trauma, was associated with lower total volume of grey matter when compared with healthy controls57. These findings support the results of previous research suggesting that higher levels of stress hormones may be associated with lower brain volumes in abuse victims58.
 

Comprehensive biological models such as the traumagenic neurodevelopmental model offer a description of the potential biological mechanism linking trauma, stress and psychosis vulnerability. Other biological models linking childhood trauma to the experience of psychotic symptoms include brain-derived neurotrophic factor59, immune-inflammatory mechanisms60 and metabolic dysregulation61. There is a general consensus that significant environmental stressors such as childhood trauma may have detrimental effects on brain development and physiological structure, resulting in the increased likelihood of experiencing psychotic symptoms62.  Many of these biological models aim to identify a clinical biomarker associated with the deleterious effects of childhood maltreatment on brain plasticity, leading to the experience of psychotic symptoms.

Psychosis treatment outcomes in patients with a history of childhood trauma

Research has consistently demonstrated that previous exposure to childhood trauma is related to the clinical manifestation of psychotic symptoms, however, relatively few studies address how trauma may impact on response to treatment in this clinical cohort. A studymeasuring early response indicators to antipsychotic treatment in first episode patients found that those who displayed poorer response to treatment more frequently reported a history of childhood trauma63. Further evidence suggests that a history of childhood adversity, in particular emotional abuse, may be associated with a poorer response to anti-psychotic medication in patients experiencing first episode psychosis64. Similarly, in a study involving 186 participants diagnosed with schizophrenia spectrum disorders, it was demonstrated that treatment-resistant patients report experiencing emotional abuse and neglect, as well as sexual abuse more frequently than the patients responding positively to anti-psychotic treatment65. These findings suggest that the experience of childhood trauma may mediate the effectiveness of anti-psychotic treatments, leading to poorer clinical outcomes for clients with a history of childhood adversities. Interestingly, one study involving 50 participants evaluating the effectiveness of an acceptance and commitment therapy intervention for individuals with a diagnosis of a psychotic spectrum disorder found that that trauma severity did not moderate the effectiveness of the intervention66. This finding highlights the different mediating roles childhood trauma may play in patient response to anti-psychotic medication versus psychological therapy treatment pathways. 

Mediating environmental factors

In addition to childhood trauma, a variety of environmental insults have been associated with an increased risk of developing a psychotic disorder. Cannabis use has been consistently highlighted in the body of research as being associated with the development of psychosis and sub-threshold psychotic experiences. One meta-analysis concluded that a relationship exists between cannabis use and the development of schizophrenia spectrum and other psychotic disorders67. This finding supports the position of previous research suggesting that cannabis use can result in the chemical disruption of brain development, resulting in the experience of psychotic symptoms. This relationship appears to be particularly strong if cannabis is used during important phases of neurological maturation such as adolescence68. Similarly, research indicates the possibility of an additive interaction between cannabis use and childhood adversities. In a study of 211 adolescents aged between 12 and 15 years, it was found that both cannabis use and childhood trauma were significantly associated with the risk of experiencing psychotic symptoms69. The presence of both childhood trauma and early cannabis use significantly increased the risk for experiencing psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a significant additive interaction between childhood trauma and cannabis use. Additionally,  the effect of sexual trauma on psychosis development has been demonstrated to be significant only for those who used cannabis under the age of 1670.


Several studies have also explored the interaction between childhood trauma and socio-economic status in order to provide a broader insight into the influence of environmental factors on the development of psychosis. A study involving 168 cases concluded that social inequity at birth was associated with a greater risk of developing a schizophrenia spectrum disorder in adulthood71. This finding is in support of previous research indicating that social deprivation during gestation and early life can increase the risk of developing a psychotic disorder72. One study involving 3,021 adolescents reported an additive effect of urbanicity, cannabis use and childhood adversities on the risk of experiencing psychotic symptoms73. Gender differences74 and lack of social support5 have also been identified as potential factors mediating the relationship between childhood trauma and psychosis. In a study of 202 individuals, women who experienced childhood trauma and had low social support were the most at risk group of developing a psychotic disorder75.


The evidence suggests that though there is a well-established association between childhood trauma and the development of psychosis, there are numerous other environmental factors that may mediate this relationship.

Clinical Implications

There are numerous clinical implications arising from of an enhanced understanding of the relationship between childhood trauma and psychosis. In terms of assessment, the research supports the inclusion of childhood trauma as a key risk factor for clinicians to explore when assessing for risk of experiencing psychotic symptoms. This may assist clinicians to conduct more robust and clinically accurate assessments, resulting in the earlier identification of clients at risk of developing psychotic symptoms. In terms of intervention, understanding the nature of the relationship between childhood trauma and psychosis may enable clinicians to develop more tailored treatment strategies for clients. Research is beginning to emerge regarding what interventions may be particularly effective for clients with a history of childhood trauma who experience psychosis. A recent meta analysis76 revealed that trauma focussed interventions have a small effect on the positive symptoms of psychosis immediately post treatment. However, these improvements were not maintained when measured again at follow up, suggesting that alternative strategies may be necessary to result in lasting positive change.

A history of childhood trauma may also be related to poorer clinical outcomes following treatment than clients who do not have a trauma history. Schäfer and Fisher26 found that clients with a diagnosis of psychosis who had previously experienced childhood adversities had a more severe clinical profile, lower levels of cognitive functioning and increased relapse rates following treatment. Similarly, Hassan and De Luca77 found that higher levels of adversities including childhood trauma increased the likelihood of clients being resistant to antipsychotic treatment. Augmenting antipsychotic treatment with psychosocial interventions such as Cognitive Behavioral Therapy has been demonstrated to be effective in improving the mental state and reducing symptom severity in treatment resistant clients experiencing psychosis with a history of childhood trauma78. This has significant clinical implications, as it suggests that multi-dimensional approaches may be more effective when treating clients with a history of childhood trauma. The research suggests that for clinicians, routine assessment of trauma histories combined with an individualized bio-psycho-social formulation and multi-dimensional individualised intervention strategies are key areas to continue to address in order to improve client outcomes.

Conclusion

In conclusion, there is significant evidence to suggest an association exists between the experience of childhood trauma and the later development of psychosis. However, there is some conflicting evidence surrounding the extent of this relationship and the types of trauma that may be associated with psychotic symptoms. The quality of the current research base suffers from several methodological issues including definition and measurement issues that need to be considered when evaluating the reliability of findings. Increased methodological rigor is necessary to further establish the complex relationship between childhood trauma and psychosis. Misiak et al.59 in their systematic review of the literature conclude that although a relationship exists between a history of childhood trauma and psychosis, childhood adversities are neither necessary nor sufficient to trigger the onset of psychosis. This statement captures the complexities of the relationship between childhood trauma and psychosis highlighted in the research base. The traumagenic neurodevelopmental model of psychosis demonstrates this complex interaction between genetic factors, biological mechanisms and environmental insults and the experience of psychotic symptoms. The research suggests that though there is a well established genetic vulnerability increasing the likelihood of psychosis, the differences in brain structure and function resulting from childhood trauma and other environmental factors play a crucial role in the onset and development of psychotic symptoms. Key clinical implications arising from the research include the importance of routine assessment of trauma histories and the delivery of multi-dimensional individualised treatment strategies in maximising client outcomes.

References

  1. Van Os, J., Kenis, G., Rutten, B.P. (2010).The environment and schizophrenia. Nature 468, 203–212.
  2. Bendall, S., Jackson, H. J., Hulbert, C. A., & McGorry, P. D. (2008). Childhood trauma and psychotic disorders: a systematic, critical review of the evidence. Schizophrenia bulletin, 34(3), 568-579. http://dx.doi.org/10.1093/schbul/sbm121
  3. Read, J., Perry, B. D., Moskowitz, A., & Connolly, J. (2001). The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry: Interpersonal and Biological Processes, 64(4), 319-345.
  4. Varese, F., Smeets, F., Drukker, M., Lieverse, R., Lataster, T., Viechtbauer, W., … & Bentall, R. P. (2012). Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective-and cross-sectional cohort     studies. Schizophrenia bulletin, 38(4), 661-671.
  5. Fisher, H. L., Jones, P. B., Fearon, P., Craig, T. K., Dazzan, P., Morgan, K., … & Murray, R. M. (2010). The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic          disorder. Psychological medicine, 40(12), 1967-1978.
  6. Sideli, L., Mule, A., La Barbera, D., & Murray, R. M. (2012). Do child abuse and maltreatment increase risk of schizophrenia?. Psychiatry investigation, 9(2), 87.
  7. Vachon, D. D., Krueger, R. F., Rogosch, F. A., & Cicchetti, D. (2015). Assessment of the harmful psychiatric and behavioral effects of different forms of child maltreatment. JAMA psychiatry, 72(11), 1135-1142.
  8. Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., … & Marks, J. S. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. American journal of preventive medicine, 14 (4): 245–258. http://dx.doi.org/10.1016/S0749-3797(98)00017-8.
  9. MacMillan, H. L., Jamieson, E., & Walsh, C. A. (2003). Reported contact with child protection services among those reporting child physical and sexual abuse: Results from a community survey. Child Abuse & Neglect, 27(12), 1397-1408.
  10. Shaw, M., & De Jong, M. (2012). Child abuse and neglect: a major public health issue and the role of child and adolescent mental health services. The Psychiatrist, 36(9), 321-325.
  11. Briere, J., & Rickards, S. (2007). Self-awareness, affect regulation, and relatedness: Differential sequels of childhood versus adult victimization experiences. The Journal of Nervous and Mental Disease, 195(6), 497-503.
  12. Fergusson, D. M., Boden, J. M., & Horwood, L. J. (2008). Exposure to childhood sexual and physical abuse and adjustment in early adulthood. Child abuse & neglect, 32(6), 607-619.
  13. MacMillan, H. L., Fleming, J. E., Streiner, D. L., Lin, E., Boyle, M. H., Jamieson, E., … & Beardslee, W. R. (2001). Childhood abuse and lifetime psychopathology in a community sample. American Journal of Psychiatry, 158(11), 1878-1883.
  14. Castellini, G., Maggi, M., & Ricca, V. (2014). Childhood sexual abuse and psychopathology. In Emotional, physical and sexual abuse (pp. 71-91). Springer, Cham.
  15. Ackner, S., Skeate, A., Patterson, P., & Neal, A. (2013). Emotional abuse and psychosis: a recent review of the literature. Journal of Aggression, Maltreatment & Trauma, 22(9), 1032-1049.
  16. Teicher, M. H., Samson, J. A., Polcari, A., & McGreenery, C. E. (2006). Sticks,          stones, and hurtful words: relative effects of various forms of childhood maltreatment. American Journal of Psychiatry, 163(6), 993-1000.
  17. Morgan, C., Kirkbride, J., Leff, J., Craig, T., Hutchinson, G., McKenzie, K., … & Murray, R. (2007). Parental separation, loss and psychosis in different ethnic groups: a case-control study. Psychological medicine, 37(4), 495-503.
  18. Schreier, A., Wolke, D., Thomas, K., Horwood, J., Hollis, C., Gunnell, D., … & Salvi, G. (2009). Prospective study of peer victimization in childhood and psychotic symptoms in a nonclinical population at age 12 years. Archives of general psychiatry, 66(5), 527-536.
  19. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Washington, D.C., American Psychiatric Association.
  20. Manning, C., & Stickley, T. (2009). Childhood abuse and psychosis; a critical review of the literature. Journal of Research in Nursing, 14(6), 531-547.
  21. Meehl, P. E. (1990). Toward an integrated theory of schizotaxia, schizotypy, and schizophrenia. Journal of Personality Disorders, 4, 1–99.
  22. Yung, A. R., Phillips, L. J., Yuen, H. P., Francey, S. M., McFarlane, C. A., Hallgren, M., & McGorry, P. D. (2003). Psychosis prediction: 12-month follow up of a          high-risk (“prodromal”) group. Schizophrenia research, 60(1), 21-32.
  23. Van Os, J., Linscott, R. J., Myin-Germeys, I., Delespaul, P., & Krabbendam, L. (2009). A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder. Psychological medicine, 39(2), 179-195.
  24. Loewy, R. L., Corey, S., Amirfathi, F., Dabit, S., Fulford, D., Pearson, R., … & Vinogradov, S. (2019). Childhood trauma and clinical high risk for psychosis. Schizophrenia research, 205, 10-14.
  25. Kraan, T., Velthorst, E., Smit, F., de Haan, L., & van der Gaag, M. (2015). Trauma and recent life events in individuals at ultra high risk for psychosis: review      and meta-analysis. Schizophrenia Research, 161(2-3), 143-149.
  26. Cunningham, T., Hoy, K., & Shannon, C. (2016). Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies. Psychosis, 8(1), 48-59.
  27. Schäfer, I., & Fisher, H. L. (2011). Childhood trauma and psychosis-what is the evidence?. Dialogues in clinical neuroscience, 13(3), 360.
  28. Shevlin, M., Houston, J. E., Dorahy, M. J., & Adamson, G. (2007). Cumulative traumas and psychosis: an analysis of the national comorbidity survey and the British Psychiatric Morbidity Survey. Schizophrenia bulletin, 34(1), 193-199.
  29. Arseneault, L., Cannon, M., Fisher, H. L., Polanczyk, G., Moffitt, T. E., & Caspi, A. (2011). Childhood trauma and children’s emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. American Journal of Psychiatry, 168(1), 65-72.
  30. Wigman, J. T. W., van Winkel, R., Ormel, J., Verhulst, F. C., Van Os, J., & Vollebergh, W. A. (2012). Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence. Acta Psychiatrica Scandinavica, 126(4), 266-273.
  31. Fisher, H. L., Craig, T. K., Fearon, P., Morgan, K., Dazzan, P., Lappin, J., … & Murray, R. M. (2011). Reliability and comparability of psychosis patients’ retrospective reports of childhood abuse. Schizophrenia Bulletin, 37(3), 546-553.
  32. Hardt, J., & Rutter, M. (2004). Validity of adult retrospective reports of adverse childhood experiences: review of the evidence. Journal of child psychology and psychiatry, 45(2), 260-273.
  33. Ajnakina, O., Trotta, A., Oakley-Hannibal, E., Di Forti, M., Stilo, S. A., Kolliakou, A., … & Pariante, C. (2016). Impact of childhood adversities on specific symptom dimensions in first-episode psychosis. Psychological medicine, 46(2), 317-326.
  34. Read, J., van Os, J., Morrison, A. P., & Ross, C. A. (2005). Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica, 112(5), 330-350.
  35. Duhig, M., Patterson, S., Connell, M., Foley, S., Capra, C., Dark, F., … & Scott, J. (2015). The prevalence and correlates of childhood trauma in patients with early psychosis. Australian & New Zealand Journal of Psychiatry, 49(7), 651-659.
  36. Muenzenmaier, K. H., Seixas, A. A., Schneeberger, A. R., Castille, D. M., Battaglia, J., & Link, B. G. (2015). Cumulative effects of stressful childhood experiences on delusions and hallucinations. Journal of Trauma & Dissociation, 16(4), 442-462.
  37. Famularo, R., Kinscherff, R., & Fenton, T. (1992). Psychiatric diagnoses of maltreated children: preliminary findings. Journal of the American Academy of Child & Adolescent Psychiatry, 31(5), 863-867.
  38. Bailey, T., Alvarez-Jimenez, M., Garcia-Sanchez, A. M., Hulbert, C., Barlow, E., & Bendall, S. (2018). Childhood trauma is associated with severity of hallucinations and delusions in psychotic disorders: a systematic review and meta-analysis. Schizophrenia       bulletin, 44(5), 1111-1122.
  39. Bentall, R. P., de Sousa, P., Varese, F., Wickham, S., Sitko, K., Haarmans, M., & Read, J. (2014). From adversity to psychosis: pathways and mechanisms from specific adversities to specific symptoms. Social psychiatry and psychiatric epidemiology, 49(7), 1011-1022.
  40. Van Dam, D. S., van Nierop, M., Viechtbauer, W., Velthorst, E., van Winkel, R., Bruggeman, R., … & Myin-Germeys, I. (2015). Childhood abuse and neglect in relation to the presence and persistence of psychotic and depressive symptomatology. Psychological Medicine, 45(7), 1363-1377.
  41. Kraan, T. C., Ising, H. K., Fokkema, M., Velthorst, E., van den Berg, D. P., Kerkhoven, M., … & Wunderink, L. (2017). The effect of childhood adversityon 4-year outcome in individuals at ultra high risk for psychosis in the Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial. Psychiatry research, 247, 55-62.
  42. Stowkowy, J., Liu, L., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., McGlashan, T. H., … & Woods, S. W. (2016). Early traumatic experiences, perceived discrimination and conversion to psychosis in those at clinical high risk for psychosis. Social psychiatry and psychiatric epidemiology, 51(4), 497-503.
  43. Peh, O. H., Rapisarda, A., & Lee, J. (2019). Childhood adversities in people at ultra-high risk (UHR) for psychosis: a systematic review and meta-analysis. Psychological medicine, 49(7), 1089-1101.
  44. Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of general psychiatry, 60(12), 1187-1192.
  45. Cannon, T. D., Kaprio, J., Lönnqvist, J., Huttunen, M., & Koskenvuo, M. (1998). The genetic epidemiology of schizophrenia in a Finnish twin cohort: a population-based modeling study. Archives of general psychiatry, 55(1), 67-74.
  46. Cannon, M., & Clarke, M. C. (2005). Risk for schizophrenia—broadening the concepts, pushing back the boundaries. Schizophrenia research, 79(1), 5-13.
  47. Misiak, B., Frydecka, D., Zawadzki, M., Krefft, M., & Kiejna, A. (2014). Refining and integrating schizophrenia pathophysiology–relevance of the allostatic load concept. Neuroscience & Biobehavioral Reviews, 45, 183-201.
  48. Myin-Germeys, I., & van Os, J. (2007). Stress-reactivity in psychosis: evidence for an affective pathway to psychosis. Clinical psychology review, 27(4), 409-424.
  49. Babenko, O., Kovalchuk, I., & Metz, G. A. (2015). Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental         health. Neuroscience & Biobehavioral Reviews, 48, 70-91.
  50. Dempster, E., Viana, J., Pidsley, R., Mill, J., 2013. Epigenetic studies of schizophrenia: progress, predicaments, and promises for the future. Schizophrenia Bulletin. 39, 11–16.
  51. Fries, E., Dettenborn, L., & Kirschbaum, C. (2009). The cortisol awakening response (CAR): facts and future directions. International journal of Psychophysiology, 72(1), 67-73.
  52. Girshkin, L., Matheson, S. L., Shepherd, A. M., & Green, M. J. (2014). Morning cortisol levels in schizophrenia and bipolar disorder: a meta-analysis. Psychoneuroendocrinology, 49, 187-206.
  53. Mondelli, V., Pariante, C. M., Navari, S., Aas, M., D’Albenzio, A., Di Forti, M., … & Papadopoulos, A. S. (2010). Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis. Schizophrenia research, 119(1-3), 75-78.
  54. Day, F. L., Valmaggia, L. R., Mondelli, V., Papadopoulos, A., Papadopoulos, I., Pariante, C. M., & McGuire, P. (2014). Blunted cortisol awakening response in people at ultra high risk of developing psychosis. Schizophrenia research, 158(1-3), 25-31.
  55. Nordholm, D., Krogh, J., Mondelli, V., Dazzan, P., Pariante, C., & Nordentoft, M. (2013). Pituitary gland volume in patients with schizophrenia, subjects at ultra high-risk of developing psychosis and healthy controls: a systematic review and meta-analysis. Psychoneuroendocrinology, 38(11), 2394-2404.
  56. Hoy, K., Barrett, S., Shannon, C., Campbell, C., Watson, D., Rushe, T., Shevlin, M., Bai,F., Cooper, S., Mulholland, C. (2012). Childhood trauma and hippocampal and amygdalar volumes in first-episode psychosis. Schizophrenia Bulletin. 38, 1162–1169.
  57. Sheffield, J. M., Williams, L. E., Woodward, N. D., & Heckers, S. (2013). Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse. Schizophrenia research, 143(1), 185-191.
  58. Haijma, S. V., Van Haren, N., Cahn, W., Koolschijn, P. C. M., Hulshoff Pol, H. E., & Kahn, R. S. (2012). Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophrenia bulletin, 39(5), 1129-1138.
  59. Theleritis, C., Fisher, H. L., Shäfer, I., Winters, L., Stahl, D., Morgan, C., … & Russo,            M. (2014). Brain derived neurotropic factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis. Schizophrenia     research, 159(1), 56-61.
  60. Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V. (2016). Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Molecular psychiatry, 21(5), 642.
  61. Mitchell, A. J., Vancampfort, D., Sweers, K., van Winkel, R., Yu, W., & De Hert, M. (2011). Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis.            Schizophrenia bulletin, 39(2), 306-318.
  62. Misiak, B., Krefft, M., Bielawski, T., Moustafa, A. A., Sąsiadek, M. M., & Frydecka, D. (2017). Toward a unified theory of childhood trauma and psychosis: a comprehensive review of epidemiological, clinical, neuropsychological and biological findings. Neuroscience & Biobehavioral Reviews, 75, 393-406.
  63. Mondelli, V., Ciufolini, S., Belvederi Murri, M., Bonaccorso, S., Di Forti, M., Giordano, A., … & Pariante, C. M. (2015). Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis. Schizophrenia bulletin, 41(5), 1162-1170.
  64. Misiak, B., & Frydecka, D. (2016). A history of childhood trauma and response to treatment with antipsychotics in first-episode schizophrenia patients: preliminary results. The Journal of nervous and mental disease, 204(10), 787-  792.
  65. Hassan, A. N., & De Luca, V. (2015). The effect of lifetime adversities on resistance to antipsychotic treatment in schizophrenia patients. Schizophrenia Research, 161(2-3), 496-500.
  66. Spidel, A., Daigneault, I., Kealy, D., & Lecomte, T. (2019). Acceptance and commitment therapy for psychosis and trauma: Investigating links between trauma severity, attachment and outcome. Behavioural and cognitive psychotherapy, 47(2), 230-243.
  67. Kraan, T., Velthorst, E., Koenders, L., Zwaart, K., Ising, H. K., van den Berg, D., … & van der Gaag, M. (2016). Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis. Psychological medicine, 46(4), 673-681.
  68. Trezza, V., Cuomo, V., & Vanderschuren, L. J. (2008). Cannabis and the developing brain: insights from behavior. European journal of pharmacology, 585(2-3), 441-452.
  69. Harley, M., Kelleher, I., Clarke, M., Lynch, F., Arseneault, L., Connor, D., … & Cannon, M. (2010). Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. Psychological medicine, 40(10), 1627-1634.
  70. Houston, J. E., Murphy, J., Adamson, G., Stringer, M., & Shevlin, M. (2008). Childhood sexual abuse, early cannabis use, and psychosis: testing an interaction model based on the National Comorbidity Survey. Schizophrenia bulletin, 34(3), 580-585.
  71. Harrison, G., Gunnell, D., Glazebrook, C., Page, K., & Kwiecinski, R. (2001). Association between schizophrenia and social inequality at birth: Case–control study. British Journal of Psychiatry, 179(4), 346-350. doi:10.1192/bjp.179.4.346
  72. Castle, D. J., Scott, K., Wessely, S., & Murray, R. M. (1993). Does social deprivation during gestation and early life predispose to later schizophrenia?. Social Psychiatry and Psychiatric Epidemiology, 28(1), 1-4.
  73. Guloksuz, S., van Nierop, M., Lieb, R., van Winkel, R., Wittchen, H. U., & van Os, J. (2015). Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology. Psychological medicine, 45(11), 2389-2401.
  74. Kocsis-Bogár, K., Mészáros, V., & Perczel-Forintos, D. (2018). Gender differences in            the relationship of childhood trauma and the course of illness in schizophrenia. Comprehensive psychiatry, 82, 84-88.
  75. Gayer-Anderson, C., Fisher, H. L., Fearon, P., Hutchinson, G., Morgan, K., Dazzan, P., … & Craig, T. K. (2015). Gender differences in the association between childhood physical and sexual abuse, social support and psychosis. Social  psychiatry and psychiatric epidemiology, 50(10), 1489-1500.
  76. Brand, R. M., McEnery, C., Rossell, S., Bendall, S., & Thomas, N. (2018). Do trauma-focussed psychological interventions have an effect on psychotic symptoms? A systematic review and meta-analysis. Schizophrenia research, 195, 13-22.
  77. Hassan, A. N., & De Luca, V. (2015). The effect of lifetime adversities on resistance to antipsychotic treatment in schizophrenia patients. Schizophrenia research, 161(2-3), 496-500.
  78. Sensky, T., Turkington, D., Kingdon, D., Scott, J. L., Scott, J., Siddle, R., … & Barnes, T. R. (2000). A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Archives of general psychiatry, 57(2), 165-172.

Author

Mark Cecchetti