Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study

Abstract

Postmortem and genetic studies have clearly demonstrated changes in GABA(B) receptors in neuropsychiatric disorders such as autism, bipolar disorder, major depression, and schizophrenia. Moreover, a number of recent studies have stressed the importance of cerebellar dysfunction in these same disorders. In the current study, we examined protein levels of the two GABA(B) receptor subunits GABBR1 and GABBR2 in lateral cerebella from a well-characterized cohort of subjects with schizophrenia (n=15), bipolar disorder (n=14), major depression (n=13) and healthy controls (n=12). We found significant reductions in protein for both GABBR1 and GABBR2 in lateral cerebella from subjects with schizophrenia, bipolar disorder and major depression when compared with controls. These results provide further evidence of GABAergic dysfunction in these three disorders as well as identify potential targets for therapeutic intervention.

Figure 1

GABBR1 and GABBR2 are reduced in lateral cerebella of subjects with schizophrenia (B), bipolar disorder (C), and major depression (D) when compared with healthy controls (A). NSE and β-actin are unchanged when compared across groups (A–D).

Figure 2

Mean GABBR1/NSE (A), GABBR1/β-actin (B), GABBR2/NSE (C), and GABBR2/β-actin (D) ratios for control, bipolar, depressed, and schizophrenic subjects are shown for cerebellum. (Error bars expressed as standard error of the mean.) *, p<0.05.