5-HT receptor-mediated Gα activation in psychiatric disorders: A postmortem study.

Objectives: Serotonin-2A (5-HT) receptors play an important role in the regulation of many brain functions that are disturbed in patients with such psychiatric diseases as mood disorders and schizophrenia. The objective of this study was to evaluate 5-HT receptor-mediated signalling pathway through Gα activation in psychiatric patients by using post-mortem brain samples.

Methods: Functional activation of Gα proteins coupled to 5-HT receptors was determined by means of [S]GTPγS binding/immunoprecipitation assay in post-mortem prefrontal cortex of psychiatric patients diagnosed as bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia, and individually matched controls. The effects of antipsychotic treatment as well as suicide were also analysed.

Results: There was no significant difference in maximum percent increase (%E) or slope factor among the four groups. The negative logarithm of concentration eliciting the half-maximal effect (pEC) was significantly reduced in BP and schizophrenia patients as compared to controls. These alterations were attributable to antipsychotic medication. The pEC values in 'non-suicide' group of schizophrenia, but not in 'suicide' group, were significantly reduced as compared with controls.

Conclusions: Altered 5-HT receptor-mediated signalling pathway through Gα proteins in prefrontal cortex might be apparently involved in pathophysiology and pharmacotherapy of BP and schizophrenia. In schizophrenic patients, these alterations as a result of successful treatment with antipsychotic agents may help in prevention of suicidal behaviour.