The Enduring Impact of Early Adversity on Psychosis Risk

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SPECIAL REPORT: SCHIZOPHRENIA & PSYCHOSIS

Over the past several decades, research has found associations between psychosis risk and different neural, genetic, and environmental metrics, but one of the strongest and most consistent risk factors is early adversity. Early adversity spans stressful and/or traumatic events, including experiences of abuse, neglect, bullying, and experiences of discrimination. By unpacking the role of early adversity on psychosis risk, we will better understand how to mitigate the lasting impact of adversity on worsening symptoms.

Evidence for Specificity in Associations

Study data consistently demonstrate a strong link between increased risk of psychosis and experiences of adversity (eg, neglect, abuse, bullying), especially in childhood and adolescence. A meta-analysis identified 36 studies, and evidence showed that childhood adversity was associated with a 2.78 increased odds of developing a psychotic disorder (95% CI, 2.34-3.31).¹ Some evidence exists that the type of early adversity may exert a differential effect on psychosis risk. Study data tend to show the strongest effects between psychosis risk and indices of early adversity associated with greater proximal stress, including forms of abuse and neglect.² Consistent with this, evidence indicates that the odds of experiencing psychosis spectrum symptoms vary by type of adversity, with significant effects stemming from experiencing sexual abuse (OR, 2.38), physical abuse (OR, 2.95), emotional abuse (OR, 3.40), bullying (OR, 2.39), and neglect (OR, 2.90).¹

There is also evidence that associations between adversity and psychosis risk may vary in strength depending on the type of schizophrenia spectrum symptom. Specifically, evidence indicates that adversity may be more strongly associated with positive symptoms (eg, unusual thought content, perceptual distortions) than with other types of schizophrenia spectrum symptoms (ie, negative, disorganized symptoms).³ Further, evidence also shows that childhood abuse (eg, sexual abuse) may be more strongly associated with perceptual distortions than with other types of schizophrenia spectrum symptoms.⁴ These findings suggest that the nature of the adversity may influence the specific manifestation of psychotic symptoms. However, more research is needed to clarify the extent to which specific forms of adversity (eg, bullying) show differential effects to specific aspects of psychosis spectrum symptoms (eg, suspiciousness).

Influential, Casual, and Biologic Factors

There is developing evidence for a causal link between adversity and psychosis, such that the experience of early adversity may lead to the development of psychosis. This evidence comes in several generally indirect forms, including evidence that the relationship between the number of adverse experiences and the risk of developing psychosis appears to be dose dependent. For example, study findings have shown that individuals with multiple adverse experiences are at a higher risk of developing psychosis compared with those with fewer or no such experiences.⁵ A study by Wicks et al using Swedish population register data found a modest linear increase in the risk of psychotic disorder for each additional indicator of childhood adversity.⁶ Other indirect causal evidence comes from research showing the link between early stress and psychotic symptoms, even when controlling for genetic risk factors.⁷ Consistent with preliminary evidence of causality and the importance of early intervention, there is also evidence that cessation of adversity impacts symptoms. Data from one study involving 1112 adolescents showed the cessation of trauma was associated with a subsequent reduction of psychotic experiences.⁸

Researchers have hypothesized why early adversity may lead to the development of psychosis spectrum symptoms. This research has begun to uncover influential factors that may either strengthen associations or partially account for the association between early adversity and psychosis. One influential theory is the role of stress in the development of psychosis spectrum symptoms. According to this theory, early adversity leads to the development of psychosis spectrum symptoms due to the negative effects of stress.⁹ Evidence indicates that early adversity may lead to heightened reactivity to stress, making individuals more susceptible to developing psychotic symptoms in response to later stressors.¹⁰ Theory posits that stress-induced changes resulting from trauma may result in altered information processing and impaired integration of trauma-related memories, which in turn may result in trauma-related perceptual distortions (eg, experiencing shadows or vague figures).¹¹ It is likely that other mental health symptoms caused by early adversity, including anxiety and depression, may lead to biased interpretations of the environment and self, which in turn lead to worsened psychosis spectrum symptoms.¹² Findings indicate persecutory ideation may develop as a result of early neglect, in turn leading to mistrust of others.¹³ Younger individuals who have experienced neglect and abuse often begin to question whether others can be trusted; if they cannot put their full trust in their caregiver, why would they trust a stranger? Thus, although there are multiple pathways in which early adversity may lead to psychosis spectrum symptoms, stress and the sequelae of stress likely play a role.

Theories also postulate that childhood adversity may interact with other preexisting biologic or genetic factors, including prenatal exposure to viral infections or genetic vulnerability, increasing the risk for psychosis.¹⁴ Support for this comes from evidence of gene-environment correlations, whereby an individual’s genes can influence the environment to which they are exposed.¹⁵ For example, genetic liability for psychosis may result in an at-risk youth being perceived as unusual by peers, leading to experiences of victimization. There is also evidence for neural regions involved in higher-order cognitive processes and processing stress associated with psychosis risk.¹⁶ However, it is notable that early adversity is associated with psychosis largely independently of genetic vulnerabilities,¹⁷ suggesting that the environment plays a significant role. Overall, the research data point to stable neural and genetic factors increasing the risk for psychosis, but it is in the context of increased exposure to adversity that this risk translates into worsening psychosis spectrum symptoms.

Clinical Implications and Recommendations

It is critical to understand the link between early adversity and psychosis, as experiencing both adversity and psychotic symptoms is associated with a greater risk for negative outcomes, including suicidality.¹⁸ Clinicians should consider several recommendations to incorporate adversity assessment into care. Mental health professionals should implement routine screening for childhood adversity when assessing individuals with psychotic symptoms. This information can guide the use of trauma-informed interventions, such as trauma-focused cognitive behavioral therapy, which has shown efficacy in reducing trauma- related psychotic symptoms.¹⁹ Researchers and clinicians should also begin developing programs aimed at preventing childhood adversity and providing support to at-risk families, actions that may eventually reduce the incidence of psychosis in the population. For example, programs may work to mitigate deprivation, reduce the incidence and consequences of bullying, and improve family communication. Mental health professionals should receive training on the impact of early adversity on mental health to improve detection and intervention strategies.

Future Research

A wealth of research findings has shown that early life adversity is one of the most robust environmental risk factors implicated in the development of psychosis. However, study data show a range of effect sizes, with the odds of developing psychotic disorders or positive psychotic symptoms ranging between 2.78 and 11.50.^1,3,7 These differences in effect sizes depend on the assessment instrument and type of early adversity; therefore, future research should continue to refine early adversity assessment instruments. Research is also needed for a better understanding of the phenomenology of trauma-related psychotic spectrum symptoms, including the degree to which trauma-related vs psychosis spectrum dissociation symptoms overlap. Research should examine how effect sizes vary depending on sample characteristics such as age and the type of adversity and symptom. Additionally, researchers should investigate how adversity interacts with other influential characteristics (eg, stress reactivity) to better inform our understanding of these associations and how early interventions may best attenuate worsening symptom trajectories. Further, it is essential to examine which resilience factors (eg, familial support) should be promoted to mitigate associations between adverse life events and psychosis risk.²⁰

In summary, the association between early adversity and the development of psychosis spectrum symptoms is well established, with indirect evidence of adversity leading to psychosis spectrum symptoms. Understanding the mechanisms underlying this association, including stress reactivity, can inform targeted interventions and preventive measures. Mental health professionals should integrate assessments of early adversity into clinical practice to enhance the identification and treatment of individuals at risk for psychosis. Researchers and practitioners should also work to implement early prevention programs to avert symptom exacerbation associated with early adversity and promote resilience factors.

Dr Karcher is an assistant professor at Washington University School of Medicine in St Louis, Missouri. Dr Karcher reports receiving support from an NIMH K23 grant.

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