Abstract
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Highlights
Psychotic disorders such as schizophrenia (SZ) have detrimental societal, economic and individual costs (Charlson et al, 2018)
The combined effect of childhood adversity and polygenic risk was greater than the sum of each alone, but the confidence interval (CI) included zero (ICR = 1.28, 95% CI −1.29 to 3.85; see Table 4, Fig. 1)
The combined effect of childhood adversities and genetic liability for schizophrenia was greater than the sum of each alone, but estimates lacked precision and CIs were wide, larger studies are needed before any firm conclusions can be drawn
Summary
Psychotic disorders such as schizophrenia (SZ) have detrimental societal, economic and individual costs (Charlson et al, 2018). A history of adversity is associated with up to a three-fold life-long increased risk of psychotic disorder with an increase in risk according to the number and severity of exposures (Aas et al, 2016; Croft et al, 2019; Varese et al, 2012) It is not known why only some exposed individuals go on to develop psychosis. A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures We investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates
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