In the largest and most nuanced meta-analysis of its kind to date, researchers have found that significant adversity during childhood is associated with an increased risk of psychotic disorder or psychotic experiences. Specifically, as a group, people with psychosis are two to three times more likely to have experienced one or multiple forms of childhood trauma compared to healthy individuals, including sexual, physical, or emotional abuse, physical or emotional neglect, bullying, or disruptions and traumas involving their parents, the study found.

This adds to a growing body of research pointing to the importance of adversity in the mental and emotional development of children and in their future mental health. Studies of the impact of major adversity on other psychiatric and mental health outcomes have observed associations of similar magnitude. For instance, the risk factor for depression in those with exposure to major childhood adversity was 2.8 times above the average level of risk in one study, and in another study, 2.6 times the average risk for bipolar disorder.

Led by BBRF 2022 Young Investigator Marieke J. H. Begemann, Ph.D., of the University of Groningen, the Netherlands, the team of investigators performing the new analysis for psychosis say their findings emphasize the importance of screening for childhood adversity when assessing individuals with psychosis or who are at risk for psychotic symptoms. Also, the team said, the results highlight the need for implementing trauma-informed psychosis therapies, as well as the importance of considering the impact of early adversity as part of established treatment protocols for psychosis. The team also included Iris E. C. Sommer, M.D., Ph.D., 2007 BBRF Independent Investigator. The paper’s first author was Lan Zhou, M.Sc., now a Ph.D. candidate.

The analysis, published in the American Journal of Psychiatry, attempts to crystalize the results of over four decades of prior research on the subject. The new meta-analysis statistically incorporates the results of 183 prior published studies involving 349,265 individuals, mainly of European extraction. The main result is very similar to that reached in an important meta-analysis published in 2012, which found a risk factor of 2.78 for childhood adversity upon risk for development of psychosis. But that study analyzed results from five times fewer studies.

The new meta-analysis takes into account a number of factors not previously incorporated in such studies, including which subtypes of adversity contribute most to increased psychosis risk; whether outcomes differ according to an individual’s sex; whether the presence of adversity affects age of psychosis onset; and how risk is impacted by distinct “dimensions” of adversity, defined as either “threats” to one’s physical or emotional integrity, or “deprivation,” i.e., absence of expected cognitive and social inputs during childhood. In the included studies, adversity had to occur prior to age 18, and included a range of subtypes.

“Our main finding confirms the increased risk of psychosis among individuals exposed to adversities early in life,” the team wrote, noting that their “odds ratio,” i.e., the factor of increased risk, at 2.80, was “strikingly similar” to that found in the 2012 meta-analysis, yet, in their view, “a more precise estimate” due to their much larger study sample.

The team found that all nine adversity subtypes they delineated were associated with increased psychosis risk, with the strongest risk factors being for emotional abuse (3.53) and physical neglect (3.26). As for the relatively large impact on psychosis risk of emotional abuse, “this is also reported for risk of other mental health outcomes,” the team pointed out.

Co-occurrence of adversity types likely being commonplace, the team said, it is important to regard them as having the capacity to reinforce one another. This is why the researchers also tried to gauge the association of childhood adversity and psychosis by aggregating adversity subtypes into the two dimensions of “threat”- and “deprivation”-based. The risk factor for deprivation turned out to be a bit stronger than that for threat.

The team’s pioneering analysis of how various kinds of adversity impacted psychosis risk among the sexes found no difference that passed statistical scrutiny, although they did note that in sheer numerical terms, there were “larger associations between psychosis and overall adversity as well as sexual abuse in women.”

In another first-time analysis, the study found that adversity-exposed psychosis patients who were included in the overall sample experienced a first psychotic episode 9-10 months earlier on average compared with psychosis patients who had not experienced childhood adversity.

The team distinguished between the associations of early adversity and psychosis that the analysis revealed and the question of what causes these associations. The current study was not designed, or able, to assess causality, although the links between adversity and psychosis are clearly complex. In terms of behavioral effects, early adversity, they noted, can directly cause insecure attachment style, cognitive biases, negative world-view, and self-stigma. At the biological level, mechanisms that can potentially translate the experience of adversity into psychosis-related pathology include epigenetic alterations (a way in which gene expression is regulated in cells); reduced levels of BDNF, a protein critical in the development and growth of the brain; and alterations in the body’s hormonal and immune responses. Still other major confounding factors may include genetic predisposition, substance use, socio-economic status, and access to education and healthcare.

As for the clinical implications of their study, the researchers said “early identification and support for individuals with a history of childhood adversity may be crucial for mitigating the risk of psychosis.” Preventive strategies to avoid childhood trauma might be particularly effective in families with high risk for psychosis (genetic risk or socioeconomic disadvantage). Other potentially useful strategies, they said, include an enriched childhood environment, development of strong coping strategies, and, in high-risk individuals, trauma-informed care, which might not only improve outcomes in psychosis but also in comorbid PTSD.