P.8.b.024 MAOA-VNTR polymorphism modulates context-dependent dopamine release and aggressive behaviour

Abstract

onset antipsychotic naive (4 cohorts; N = 133), individuals with Asperger syndrome were drug free (1 cohort; N = 30), and bipolar disorder (7 cohorts; N = 90) and major depression patients (4 cohorts; N = 119) were receiving medication and were at various stages of illness. We found a number of distinct and overlapping sex-specific markers associated with each illness by evaluating the sex-diagnosis interaction for each analyte in a linear model. In particular, we found male-specific increases in the levels of several inflammatory markers in schizophrenia, major depression and Asperger syndrome. These markers included a number of interleukins, intercellular adhesion molecule 1, alpha-1-antitrypsin, and others, raising the possibility that some aspects of the widely reported immunological abnormalities in psychiatric illness [3] are male-specific. In line with the numerous sex differences reported in schizophrenia, our findings in first episode antipsychotic naive schizophrenia included alterations in the levels of several hormones, including elevated free and total testosterone in female patients and concomitant sex differences in sex hormone binding globulin (SHBG) and prolactin concentrations. Previous studies of chronic schizophrenia have similarly found long-term antipsychotic use to be associated with hyperprolactinaemia in females and a hypogonadal state [2]. In addition, we found that SHBG levels were also reduced in females with Asperger syndrome, pointing again to higher levels of free testosterone and overall to sex-specific hormonal disturbances in Asperger syndrome and in chronic and first episode schizophrenia. Other findings included female specific alterations of markers related to lipid metabolism in Asperger syndrome, increased levels of markers related to oxidative stress in males with bipolar disorder, and disruptions in serum levels of cardiovascular factors in schizophrenia. We conclude that different molecular mechanisms may be involved in the pathophysiology of these conditions, with implications for how we study and treat psychiatric illnesses and developmental disorders.