Attractin Participates in Schizophrenia by Affecting Testosterone Levels.

Attractin (ATRN) is a widely expressed glycoprotein that is involved in energy homeostasis, neurodevelopment, and immune response. It is encoded by a gene spanning 180 kb on chromosome 20p13, a region previously implicated in schizophrenia by linkage studies. To address a possible role of in disorders of the central nervous system, we created an knockout zebrafish line and performed behavioral tests. Adult zebrafish exhibited more pronounced attack behavior relative to wild-type control zebrafish in a tracking analysis. Biochemical analysis revealed elevated testosterone levels in zebrafish. At the gene expression level, we noted an upregulation of and , key proteins in testosterone synthesis in the brains of both adult and larvae of zebrafish. In order to further elucidate the relationship between testosterone and behavioral syndromes, we then compared testosterone levels of 9,008 psychiatric patients and 247 healthy controls from the same catchment area. Of all subjects examined, male subjects with schizophrenia exhibited lower testosterone levels compared with controls. In contrast, female subjects with a diagnosis of schizophrenia or bipolar disorder featured higher testosterone levels than did same sex controls. Purposeful sampling of extreme groups showed reduced expression in a subset of these subjects. Finally, we identified 14 subjects with mutations. All of whom displayed abnormal testosterone levels. In summary, the interplay of and testosterone may help to explain sexual dimorphisms in selected behavioral phenotypes.