Primary and Readjudication Mortality Results From Zodiac, a Large Simple Trial of Ziprasidone vs. Olanzapine in Patients With Schizophrenia (original) (raw)

2010, Schizophrenia Research

Background: Recent studies have suggested that early adverse events, such as childhood trauma, accentuate vulnerability for psychosis, and stressful life events, occurring later in the vulnerable individual may move the individual towards the tipping point of psychosis. This would, alongside the contribution of genetic factors, suggest that environment x environment (ExE) interactions play a decisive role in psychosis development, with vulnerability being determined by cascading events within the stress-trauma pathogen. However, establishing causality of these environmental dynamics requires prospective studies that are adequately powered, which are currently lacking in the literature. The Early Developmental Stages of Psychopathology (EDSP) study, a longitudinal study of a population sample of 3021 adolescents and young adults, was designed to provide answers about prevalence, incidence, risk factors, comorbidity and course of mental disorders. We used data from this study to examine whether there was a synergistic interaction between early life trauma and occurrence of later life events on the risk of outcome of psychosis, taking into account the moderating or mediating effects of cannabis abuse and urbanicity. Methods: We analyzed the association between childhood trauma (retrospectively assessed at T0), negative life events occurring between T0 and T2, and psychosis at T3, defined as either (i) having a total score above the 90th centile on the psychoticism subscale of the SCL-90, or (ii) having displayed impairment or helpseeking behavior in response to the occurrence of psychotic symptoms at T3, or (iii) being diagnosed as having a psychotic disorder at T3, according to the explicit diagnostic criteria of the DSM-IV. Associations were expressed as odds ratios from logistic regression models. All analyses were a priori adjusted for age, sex, urbanicity and cannabis abuse. Furthermore, all participants fulfilling criteria for psychosis liability prior to T3 were excluded from analysis. Results: The experience of life events between T0 and T2 significantly increased the risk to develop psychosis at T3 (OR: 2.37; 95% CI: 1.68-3.38; p = .000). This risk was larger in subjects who were exposed to trauma in their childhood (OR: 5.92; 95% CI: 2.41-14.57; p = .000), compared to those who did not experience childhood trauma (OR: 1.88; 95% CI: 1.25-2.82; p = .002). The observed risk difference in the trauma group was significantly larger than the risk difference in the non-trauma group (14,9% and 4,4% resp.; test for interaction: χ2(df = 1676) = 7.59, p = .006). Discussion: Results from this longitudinal study indicate that the occurrence of early life trauma moderates the effect of later life events on the risk of psychosis, taking into account the moderating