Interaction Effects of Season of Birth and Cytokine Genes on Schizotypal Traits in the General Population.

Literature suggests that the effect of winter birth on vulnerability to schizophrenia might be mediated by increased expression of proinflammatory cytokines due to prenatal infection and its inadequate regulation by anti-inflammatory factors. As the response of the immune system depends on genotype, this study assessed the interaction effects of cytokine genes and season of birth (SOB) on schizotypy measured with the Schizotypal Personality Questionnaire (SPQ-74). We searched for associations of rs16944, rs2243250, and VNTR polymorphisms, SOB, and their interactions with the SPQ-74 total score in a sample of 278 healthy individuals. A significant effect of the X SOB interaction was found, = 0.007 and = 0.028. We confirmed this effect using an extended sample of 373 individuals. Homozygotes CC born in winter showed the highest SPQ total score and differed significantly from winter-born T allele carriers, = 0.049. This difference was demonstrated for cognitive-perceptual and disorganized but not interpersonal dimensions. The findings are consistent with the hypothesis that the cytokine genes by SOB interaction can influence variability of schizotypal traits in the general population. The T allele appeared to have a protective effect against the development of positive and disorganized schizotypal traits in winter-born individuals.