Over the past 2 years, several specific genes have been convincingly associated with
schizophrenia risk in a number of populations around the world. Some of the genes that have been studied more extensively include:
catechol O-methyltransferase (COMT) (chromosome 22q),
dysbindin-1 (chromosome 6p),
neuregulin 1 (chromosome 8p),
metabotropic glutamate receptor 3 (GRM-3) (chromosome 7q),
glutamate decarboxylase 1 (chromosome 2q), and disrupted-in-
schizophrenia 1 (DISC1) (chromosome 1q). A functional polymorphism in the COMT gene, which affects prefrontal cortical function by changing
dopamine signaling in the prefrontal cortex, has been studied extensively. This gene impacts the regulation of
dopamine neuronal activity in the brainstem, which is associated with
psychosis. GRM-3 shows similar results on prefrontal function; in postmortem tissue, it has an effect on expression of various
glutamate synaptic markers. DISC1 affects hippocampal anatomy and function, whereas
dysbindin-1 appears to be a general cognitive capacity gene that is underexpressed in the schizophrenic cortex. Data suggest that these susceptibility genes influence the cortical information processing which characterizes the schizophrenic phenotype. These data add to the evidence that such genes contribute to the pathophysiology of
schizophrenia and provide insights into their mechanisms. Thus, genetic variation and its influence on the biological processes underlying
schizophrenia may be key to developing future prevention strategies and new treatments.