Meta-regression analysis using latitude as moderator of paternal age related schizophrenia risk: High ambient temperature induced de novo mutations or is it related to the cold?

While the season of birth, latitude and first admission effects suggest higher risk of schizophrenia with cold climate, the high ambient temperature induced de novo mutation hypothesis suggests the opposite. We conducted a systematic review and meta-analysis (4 case-control studies and 5 cohort studies). We used annual mean daily temperature and latitude of study sites as direct and indirect measures of ambient temperature respectively. Using case-control studies conducted in the Northern hemisphere for meta-regression, high latitude and low ambient temperature were found to increase paternal age related schizophrenia risk significantly. More research is needed to support the de novo mutation hypothesis.