Dysfunctional brain networks and genetic risk for schizophrenia: specific neurotransmitter systems

Multiple neurotransmitter circuits are disturbed in schizophrenia, and the dopamine hypothesis of schizophrenia prevails as the hypothesis with most empirical support. On the other hand, schizophrenia is highly heritable with a pattern consistent with both common and rare allelic variants and gene × environment interaction. Advances in the field of neuroimaging have expanded our knowledge of intermediate phenotypes, the neurobiological processes that convey the risk from the genes to the complex phenotype. In this article, we review the recent and continuously accumulating evidence from in vivo imaging studies aiming at characterizing neurochemical intermediate phenotypes of schizophrenia. Dopaminergic alterations in schizophrenia are shared by individuals at genetic risk who do not express the illness, suggesting a "dopamine hypothesis of schizophrenia vulnerability." This hypothesis has the potential to help us better understand the dopaminergic dysfunction in the context of the complex pathophysiological process leading to schizophrenia. In the future, neurotransmitter imaging studies should investigate the gene × environment interaction in schizophrenia, and try to identify neurobiological correlates of heightened sensitivity to environmental stressors (e.g., cannabis, childhood trauma, and other psychosocial stress) in genetically vulnerable individuals.