Bipolar disorder.

Bipolar disorder's unique combination of three characteristics - clear genetic diathesis, distinctive clinical features, early availability of an effective treatment (lithium) - explains its special place in the history of psychiatry and its contribution to the current explosive growth of neuroscience. This article looks at the state of the art in bipolar disorder from the vantage point of: (i) genetics (possible linkages on chromosomes 18 and 21q, polygenic hypothesis, research into genetic markers); (ii) diagnosis (new focus on the subjective aspects of bipolar disorder to offset the current trend of underdiagnosis due to overreliance on standardized interviews and rating scales); (iii) outcome (increase in treatment-resistant forms signaling a change in the natural history of bipolar disorder); (iv) pathophysiology (research into circadian biological rhythms and the kindling hypothesis to explain recurrence); (v) treatment (emergence of the anticonvulsants, suggested role of chronic antidepressant treatment in the development of treatment resistance); (vi) neurobiology (evaluation of regulatory function in relation to affective disturbances, role of postsynaptic second-messenger mechanisms, advances in functional neuroimaging); and (vii) psychosocial research (shedding overly dualistic theories of the past to understand the mind and brain as an entity, thus emphasizing the importance of balancing the psychopharmacological and psychotherapeutic approaches). Future progress in the understanding and treatment of bipolar disorder will rely on successful integration of the biological and psychosocial lines of investigation.