GABAAand GABABreceptor dysregulation in superior frontal cortex of subjects with schizophrenia and bipolar disorder.
Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAAand two GABABreceptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls. Analyses of Variance (ANOVAs) identified significant group effects for protein levels for the α1, α6, β1, β3, δ, ɛ, and π GABAAreceptor subunits and R1 and R2 GABABreceptor subunits. Follow-up t tests confirmed changes for these subunits in subjects with schizophrenia, subjects with bipolar disorder, or both groups. Alterations in stoichiometry of GABA receptor subunits could result in altered ligand binding, transmission, and pharmacology of GABA receptors in superior frontal cortex. Thus, impaired GABAergic transmission may negatively contribute to symptoms such as anxiety or panic as well as impaired learning and information processing, all of which are disrupted in schizophrenia and bipolar disorder. Taken together, these results provide additional evidence of GABAergic receptor abnormalities in these disorders.
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, MMC 392, Minneapolis, Minnesota, 55455.|Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, Minnesota, 55455.
S Hossein
0000-0002-6859-2626
SH
Fatemi
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, MMC 392, Minneapolis, Minnesota, 55455.
Timothy D
TD
Folsom
Department of Psychiatry, VA Medical Center, 1 Veterans Drive Minneapolis, Minnesota, 55417-2399.
Paul D
PD
Thuras
D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D015153:Blotting, Western; D015331:Cohort Studies; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism
D011619:Psychotropic Drugs; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B
GABRɛ; GABRα1; GABRα6; bipolar disorder; schizophrenia