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

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.

Obstetric complications and psychopathology in schizophrenia: A systematic review and meta-analysis.

Schizophrenia (SZ) is a severe mental health condition involving gene-environment interactions, with obstetric complications (OCs) conferring an elevated risk for the disease. Current research suggests that OCs may exacerbate SZ symptoms. This study conducted a systematic review and meta-analysis to comprehensively evaluate differences in psychopathology between individuals with and without exposure to OCs in relation to SZ and related disorders. We systematically searched PubMed, PsycINFO, and SCOPUS to identify eligible studies. A total of 4091 records were retrieved through systematic and citation searches. 14 studies were included in the review, and 12 met the criteria for meta-analysis, involving 2992 patients. The analysis revealed that SZ patients who had been exposed to OCs exhibited significantly higher levels of positive symptoms (SMD=0.10, 95 %CI=0.01,0.20; p=0.03), general psychopathology (SMD=0.37, 95 %CI=0.22,0.52; p<0.001), total clinical symptomatology (SMD=0.44, 95 %CI=0.24,0.64; p<0.001) and depressive symptoms (SMD=0.47, 95 %CI=0.09,0.84; p=0.01). No significant differences were found in negative symptomatology and functioning. Our results suggest that OCs are not only associated with an increased risk of developing psychosis but with more severe symptomatology.

Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers.

CONTEXT: Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL). METHODS: Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point. RESULTS: Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject. CONCLUSIONS: In absence of HIV infection, or concomitant treatment, short-term exposure to T20 or RAL in healthy adult volunteers did not lead to any indicative changes in toxicity markers thus presuming the safe profile of both drugs.