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Are familial liability for schizophrenia and obstetric complications independently associated with risk of psychotic illness, after adjusting for other environmental stressors in childhood?

Objective: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. Methods: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980–1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). Results: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5–7.2 to hazard ratio: 3.5, confidence interval: 2.8–4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0–1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. Conclusion: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability.