Affective psychosis and childhood trauma

In our study severely sexually abused people with first-episode psychosis had a five-fold higher likelihood of receiving a diagnosis of affective psychosis. Our results are in line with previous studies, which showed an increased presence of psychotic features in both major depressive disorder and bipolar affective disorder when the person had been abused. ^{Reference Gaudiano and Zimmerman5,Reference Upthegrove, Chard, Jones, Gordon-Smith, Forty and Jones6,Reference Hammersley, Dias, Todd, Bowen-Jones, Reilly and Bentall23} Affective symptoms could mediate the victimisation-psychosis association. Our data are consistent with previous studies, ^{Reference Garety, Bebbington, Fowler, Freeman and Kuipers24,Reference Gracie, Freeman, Green, Garety, Kuipers and Hardy25} which advocate a significant role of negative beliefs about self and others and of depression and anxiety within the pathway from early trauma to psychosis. Most interestingly, only sexual abuse – not physical abuse – has been proved to be a strong and specific risk factor for mental disorders, including major depression and anxiety disorder, ^{Reference Fergusson, McLeod and Horwood26} once more supporting our results. A recent study described a significant association between sexual abuse and depressive symptoms in women but not in men, suggesting that maltreatments may have a gender effect on the development of maladaptive self-images and depression, ^{Reference Haug, Oie, Andreassen, Bratlien, Nelson and Aas27} mediated by a gender difference in stress reactivity. Women have been shown to be more susceptible to the negative consequences of stress in general, ^{Reference Myin-Germeys, Krabbendam, Delespaul and Van Os28} and of early traumatic experiences in particular. ^{Reference Myin-Germeys and Van Os29} In contrast, we did not find any effect of gender on the association between severe sexual abuse and affective psychosis. Our study did not investigate the presence of depressive symptoms but focused on diagnostic category; issues other than gender might therefore be involved and explain the discrepancy with previous evidence.

Substance use and childhood trauma

In our sample, drug use was found to be associated with both severe sexual and severe physical abuse. Traumatised participants – in particular, those reporting severe childhood sexual abuse – showed significantly higher lifetime cannabis use. The trauma-cannabis-psychosis association could involve several psychosocial elements, contributing to an enhanced vulnerability, ^{Reference Houston, Murphy, Shevlin and Adamso8} and various biological factors, including the dopamine neurotransmitter system, ^{Reference Kaufman, Plotsky, Nemeroff and Charney30} and the hypothalamic-pituitary-adrenal (HPA) axis. ^{Reference Mondelli, Dazzan, Hepgul, Di Forti, Aas and D'Albenzio2} First, childhood trauma has been significantly associated with depression, which usually precedes the onset of substance dependence among traumatised people. ^{Reference Douglas, Chan, Gelernter, Arias, Anton and Weiss31} Consistent with this, abused individuals in our sample more frequently received a diagnosis of affective psychosis when compared with those who were not abused. We may therefore propose the role of affective symptoms as mediators or modulators of the trauma-cannabis-psychosis association. Abused people tend to become more frequently depressed and thus might more frequently use cannabis to alleviate depressive symptoms, or could develop dysfunctional coping strategies such as self-medication to reduce trauma-related stress. ^{Reference Houston, Murphy, Shevlin and Adamso8} Second, social factors might have a meaningful influence: disadvantaged environments, where it is easier to become entrapped in substance dependence, and social adversities, such as a low socioeconomic status and unemployment, have been shown to be significantly associated with both psychosis and childhood trauma. ^{Reference Wicks, Hjern, Gunnell, Lewis and Dalman32} Finally, it is a reasonable hypothesis that abused and non-abused individuals have similar drug use patterns but that only the former develop psychosis owing to their pre-existing enhanced vulnerability. ^{Reference Houston, Murphy, Shevlin and Adamso8,Reference Tosato, Lasalvia, Bonetto, Mazzoncini, Cristofalo and De Santi33}

Biological factors may also be involved. First, and in line with the ‘sensitisation’ hypothesis, genetically predisposed individuals, whether exposed to environmental risk factors (as childhood trauma and cannabis use) or not, have been proved to show an increased dopaminergic response to social stressors. It may lead to stable changes in the stress-related dopaminergic response system, ^{Reference Collip, Myin-Germeys and Van Os34} and eventually to a subsequent enhanced vulnerability for psychosis. Second, animal studies have shown an influence of environmental stressors on a rat's delta-tetrahydrocannabinol (ΔTHC) response: ^{Reference Suplita, Eisenstein, Neely, Moise and Hohmann35} under stressful housing conditions (i.e. isolation and food deprivation) ΔTHC administration resulted in an increased dopamine uptake and significant behavioural abnormalities not observed in control group rats. ^{Reference MacLean and Littleton36} Finally, early traumatic experiences have been associated with permanent HPA axis overreactivity (higher levels of Cortisol) to stressors and changes in brain structures. ^{Reference Read, Perry, Moskowitz and Connolly37} Moreover, we found that both sexual and physical severe abuse experiences were significantly associated with heroin lifetime use, whereas cocaine lifetime use appeared to be associated only with severe physical abuse, which is to some degree in line with results for other psychiatric disorders (anxiety, mood and borderline personality disorders). ^{Reference Banducci, Hoffman, Lejuez and Koenen38} Our findings seem to contrast with a recent study that found no association between childhood trauma and use of cannabis or other illicit drugs. ^{Reference Duhig, Patterson, Connell, Foley, Capra and Dark39} This inconsistency might be partially explained by the different time frame used when investigating substance use: we explored lifetime use, whereas the other study investigated substance use in the preceding month.

Strengths and limitations

The GET UP PIANO trial is the first trial in first-episode psychosis patients performed in a large catchment area, corresponding to nearly 10 million inhabitants. Over 90% of CMHCs completed the study, demonstrating that the participants were highly representative of the patients treated in the community psychiatric services. We used reliable, internationally validated instruments and adopted conservative cut-off points, previously applied, to identify only the most severe forms of abuse. Moreover, we systematically performed adjustments excluding the gender effect, known to represent a potential confounder on the association between trauma and psychosis. ^{Reference Fisher, Morgan, Dazzan, Craig, Morgan and Hutchinson40}

However, some limitations should also be considered. Reliance on the retrospective reporting of abuse might increase the risk of recall bias. However, the reliability of patients affected by psychosis in referring trauma has been clearly demonstrated; ^{Reference Fisher, Craig, Fearon, Morgan, Dazzan and Lappin41} their reports were independent of symptoms, stable over time and generally consistent with other sources of information. It has also been proved that retrospective recall yields an underestimation of the phenomenon, rather than an overestimation. ^{Reference Hardt and Rutter42} Despite clear evidence of association between trauma, cannabis and psychosis, our data do not elucidate whether childhood traumatic experiences and drug misuse represent vulnerability factors for psychosis or environmental stressors that trigger the disorder acting on a pre-existing vulnerability. Traumatic experiences and drug misuse could both be vulnerability agents, decreasing the individual's resilience in response to other stressors such as migration, and leading to psychosis. They might represent two different environmental stressors, acting – in an additive or multiplicative way – on another type of vulnerability (possibly genetic). Childhood trauma could enhance vulnerability and cannabis use acts as an exacerbating agent or vice versa. Finally, because of the relative rarity of abusive experiences, resulting in small numbers, no further adjustments for social factors (such as employment or socioeconomic status) and/or genetic vulnerability (familiality) have been carried out in the analysis.

Future research

In addition to clarifying whether cannabis and childhood trauma represent vulnerability factors or stressors triggering psychosis, studies should also analyse this association, taking into account other environmental variables and/or biological markers. A population-based, longitudinal prospective study design, with long-term follow-up (from infancy to adulthood) would be most appropriate. ^{Reference Poulton, Moffitt and Silva43} Overall, our study suggests that patients with first-episode psychosis exposed to childhood trauma constitute a distinctive subgroup characterised by diverse features in terms of nosology and drug use. It has elucidated, albeit partially, to what extent the presence of childhood trauma affects features of first-episode psychosis. Finally, this study may provide some important hints for specific therapeutic and/or preventive interventions, which might carry within themselves an enhanced impact on illness course, outcomes and prognosis.