Are some genetic risk factors common to schizophrenia, bipolar disorder and depression? Evidence from DISC1, GRIK4 and NRG1.
Depression is common in patients with schizophrenia and it is well established from family studies that rates of depression are increased among relatives of probands with schizophrenia, making it likely that the phenotypes described under the categories of affective and non-affective psychoses share some genetic risk factors. Family linkage studies have identified several chromosomal regions likely to contain risk genes for schizophrenia and bipolar disorder, suggesting common susceptibility loci. Candidate gene association studies have provided further evidence to suggest that some genes including two of the most studied candidates, Disrupted in Schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1) may be involved in both types of psychosis. We have recently identified another strong candidate for a role in both schizophrenia and affective disorders, GRIK4 a glutamate receptor mapped to chromosome 11q23 [Glutamate Receptor, Ionotropic, Kainate, type 4]. This gene is disrupted by a translocation breakpoint in a patient with schizophrenia, and case control studies show significant association of GRIK4 with both schizophrenia and bipolar disorder. Identifying genes implicated in the psychoses may eventually provide the basis for classification based on biology rather than symptoms, and suggest novel treatment strategies for these complex brain disorders.
Blackwood
Douglas H R
DH
Division of Psychiatry, The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK. d.blackwood@ed.ac.uk
Pickard
Ben J
BJ
Thomson
Pippa A
PA
Evans
Kathryn L
KL
Porteous
David J
DJ
Muir
Walter J
WJ
D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D003863:Depression / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D018092:Kainic Acid Receptors / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D018092:Kainic Acid Receptors; C412476:DISC1 protein, human; C514872:GRIK4 protein, human; C094131:NRG1 protein, human