GABAergic Hypofunction

Gamma-aminobutyric acid is the principal inhibitory neurotransmitter of the brain. There is considerable evidence for a decreased activity of the GABAergic system in patients with schizophrenia (Bunney et al., 1997; Selemon, 2001). Various studies have reported a decrease in GABA content, a decrease in GABA uptake sites, a decrease in the synthesizing enzyme for GABA (the 67 kd isoform of glutamic acid decarboxylase—GAD67), a decrease in the GABA transporter (GAT), and a concomitant up-regulation of GABAA receptors. A down-regulation of GABAergic activity may have wide-ranging effects since the columnar firing pattern of cortical neurons is determined by a fine balance of glutamatergic excitation and GABAergic inhibition. Cortical malfunction is one of the hallmarks of schizophrenia.

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