title: Signal transduction pathways in the pathophysiology of bipolar disorder.
abstract: Signal transduction pathways and genes associated with cellular life and death have received much attention in bipolar disorder (BPD) and provide scientists with molecular targets for understanding the biological basis of BPD. In this chapter, we describe the signal transduction pathways involved in the molecular biology of BPD and the indications for the mechanisms of disease and treatment. We discuss the BPD literature with respect to the disease itself and the effects of mood stabilizer treatment on cellular receptors, including G-protein-coupled receptors, glutamate receptors, and tyrosine receptor kinase. We also discuss the intracellular alterations observed in BPD to second messenger systems, such as cyclic adenosine monophosphate (cAMP), protein kinase A, phosphoinositide pathways, glycogen synthase kinase-3, protein kinase B, Wnt, and arachidonic acid. We describe how receptor activation and modulation of second messengers occurs, and how transcription factors are activated and altered in this disease (e.g., the transcription factors ?-catenin, cAMP response element binding protein, heat shock transcription factor-1, and activator protein-1). Abnormalities in intracellular signal transduction pathways could generate a functional discrepancy in numerous neurotransmitter systems, which may explain the varied clinical symptoms observed in BPD. The influence of mood stabilizers on transcription factors may be important in connecting the regulation of gene expression to neuroplasticity and cellular resilience.
authors.affiliation: Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 2A1, jeremy.gawryluk@ubc.ca.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Gawryluk
authors.forename: L Trevor
authors.initials: LT
authors.lastname: Young
mesh_terms: D001714:Bipolar Disorder / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D015290:Second Messenger Systems; D015398:Signal Transduction