Expression of GABAA α2-, β1-and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder

There is abundant evidence that dysfunction of the gamma-aminobutyric acid (GABA)ergic signaling system is implicated in the pathology of schizophrenia and mood disorders. Less is known about the alterations in protein expression of GABA receptor subunits in brains of subjects with schizophrenia and mood disorders. We have previously demonstrated reduced expression of GABA(B) receptor subunits 1 and 2 (GABBR1 and GABBR2) in the lateral cerebella of subjects with schizophrenia, bipolar disorder and major depressive disorder. In the current study, we have expanded these studies to examine the mRNA and protein expression of 12 GABA(A) subunit proteins (alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, beta 1, beta 2, beta 3, delta, epsilon, gamma 2 and gamma 3) in the lateral cerebella from the same set of subjects with schizophrenia (N = 9-15), bipolar disorder (N = 10-15) and major depression (N = 12-15) versus healthy controls (N = 10-15). We found significant group effects for protein levels of the alpha 2-, beta 1- and epsilon-subunits across treatment groups. We also found a significant group effect for mRNA levels of the alpha 1-subunit across treatment groups. New avenues for treatment, such as the use of neurosteroids to promote GABA modulation, could potentially ameliorate GABAergic dysfunction in these disorders.