The Neurobiology of Bipolar Disorder: Focus on Signal Transduction Pathways and the Regulation of Gene Expression

Abstract

Objective: This article presents an overview of signal transduction path ways and re views the re search under taken to study these systems in clinically relevant samples from patients with bipolar disorder (BD). Method: We re viewed the published findings from studies of post mortem brain tissue and blood samples from patients with BD. Results: Al though the ex act biochemical abnormalities have yet to be identified, the presented findings strongly suggest that BD may be due, at least in part, to abnormalities in signal transduction mechanisms. In particular, altered levels or function, or both, of G-protein a subunits and effector molecules such as protein kinase A (PKA) and protein kinase C (PKC) have consistently been associated with BD both in peripheral cells and in post mortem braintis sue, while more re cent studies implicate disruption in novel second-messenger cascades, such as the ERK/MAPK path way. Conclusions: De spite the difficulties inherent in biochemical studies of clinically relevant tissue samples, numerous investigations have illuminated the signal transduction mechanisms in patients with BD. These studies also suggest that BD may be due to the interaction of many abnormalities. In this con text, novel techniques enabling the study of gene expression promise to assist in untangling these complex interactions, through visualizing the end result of these changes at the level of gene transcription.