Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: a blood test for manic depressive disease?

gamma-Aminobutyric acid (GABA), an inhibitory neurotransmitter that serves about one-third of brain neurons, is involved in the development of depression and in the treatment of depression and mania with pharmacological therapy. Brain activity of GABA may be conveniently measured in plasma, and changes in plasma concentrations of GABA reflect brain GABA activity. Plasma concentrations of GABA are significantly lower than control values in about one-third of patients with major depressive disorder; concentrations are also low in patients with mania and in bipolar patients who are depressed. These low concentrations of GABA appear to persist after recovery from depression and are not increased by treatments that improve depressive symptoms. Follow-up studies suggest that GABA concentrations remain relatively constant over at least 4 years. Additionally, preliminary data suggest that low plasma GABA is a familial marker of mood disorders in a subset of patients. Despite the difficulty of demonstrating that a particular biochemical measure is a true genetic trait marker for vulnerability for development of an illness, the accumulated data suggest that low plasma GABA may represent a biological marker of vulnerability for development of various mood disorders.