The underlying neurobiology of bipolar disorder.

Clinical studies over the past decades have attempted to uncover the biological factors mediating the pathophysiology of bipolar disorder (BD) utilizing a variety of biochemical and neuroendocrine strategies. Indeed, assessments of cerebrospinal fluid chemistry, neuroendocrine responses to pharmacological challenge, and neuroreceptor and transporter binding have demonstrated a number of abnormalities in the amine neurotransmitter systems in this disorder. However, recent studies have also implicated critical signal transduction pathways as being integral to the pathophysiology and treatment of BD, in addition to a growing body of data suggesting that impairments of neuroplasticity and cellular resilience may also underlie the pathophysiology of the disorder. It is thus noteworthy that mood stabilizers and antidepressants indirectly regulate a number of factors involved in cell survival pathways - including MAP kinases, CREB, BDNF and bcl-2 protein - and may thus bring about some of their delayed long-term beneficial effects via underappreciated neurotrophic effects.