Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis

Abstract

Background Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. Study Design 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis‐Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS‐SZ) and interactions between these. Results Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS‐SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. Conclusions We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.

Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study

“…In summary, we have identified a causal effect of placental impairment in broadly defined depression, probably reflecting an unspecific psychopathology. This adds new data on the current debate about placental role in mental health (21,56,65,66). Although no treatments for fetal growth restriction are currently available, there are several promising agents on clinical trials or preclinical research, acting on processes such as oxygen supply by angiogenesis or vasodilatation, or mitigation of oxidative stress (67,68).…”

“…However, it was not replicated in a larger independent study (20). The lack of replication may be due to a type I error or to the use of different scales to measure obstetric complications at each study (12,21). PlacPRS was also negatively associated with neonatal brain volume and cognitive development at 1 year (22).…”

Anthropometry in antipsychotic-naïve first-episode psychosis patients: An exploratory approach to the role of environmental early life events in two independent samples

“…This model has been translated into the mental health realm (Garcia-Rizo et al, 2015) suggesting that adverse influences during early development (obstetric complications-OCs) might underlie the later development of medical conditions, such as glucose abnormalities in serious mental illness (Garcia-Rizo et al, 2016). Different kinds of stressful events (Valli et al, 2023), such as infections, placental abnormalities, emotional stress, under-nutrition or famine (Hoek et al, 1998;Jones, 1994;Susser and Lin, 1992), or alcohol or tobacco exposure (Arango et al, 2021;Davies et al, 2020) impact the fetus, at different stages of its maturation and development, implying different consequences in the short and long term as an epiphenomena (Garcia-Rizo and Bitanihirwe, 2020). Previous prenatal model has important implications as a theoretical explanation for the increased morbidity and early mortality of patients.…”