S t a t e
o f t h e a r to approach the state of the art in diagnosis
andtreatment of
bipolar disorder requires a review of the cur-rent
state of both research and practice. There is no doubtthat
bipolar disorder has been an especially importantand illustrative field of research in
the evolution of psy-chiatry.
Consider the history of the discovery of lithium.It
is a classic example of an alert investigator with bothbasic
science and clinical interests seeing the potential ofan
unexpected laboratory observation. Recent diagnosticresearch,
in which controversy abounds regarding under-diagnosis
and misdiagnosis of bipolar disorder, illus-trates the richness of the clinical
relevance of contempo-rary
diagnostic and nosological research. Other aspectsof current research that are relevant
to diagnostic validityinclude
genetic and outcome research. With respect
totreatment,
there are controversies regarding the use
ofmood-stabilizing
agents, and dilemmas in the use of anti-depressant
agents in bipolar disorder. In terms of theoriesof
the pathogenesis of bipolar illness, neurobiologicalresearch and theories have
advanced, with the kindlinghypothesis
in particular seeming useful as a general the-ory
of the pathophysiology of bipolar disorder. In addi-tion,
integrative research that includes attention to
thepsychosocial
aspects of bipolar disorder appears on theverge
of full development.Keywords: bipolar
disorder; manic-depressive illness; mood disorder; depression; research; diagnosis;
treatment; genetics; neurobiology; outcomeBipolar
disorder's unique combination of three characteristics—clear genetic diathesis,
distinctive clinicalfeatures,
early availability of an effective treatment (lithium)—explains its special
place in the history ofpsychiatry
and its contribution to the current explosive growth of neuroscience. This article
looks at thestate
of the art in bipolar disorder from the vantage point of: (i) genetics
(possible linkages on chromo-somes
18 and 21q, polygenic hypothesis, research into genetic markers); (ii) diagnosis
(new focus on thesubjective
aspects of bipolar disorder to offset the current trend of underdiagnosis due
to overreliance onstandardized
interviews and rating scales); (iii) outcome (increase
in treatment-resistant forms signaling achange
in the natural history of bipolar disorder); (iv) pathophysiology
(research into circadian biologicalrhythms
and the kindling hypothesis to explain recurrence); (v) treatment
(emergence of the anticonvul-sants,
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 postsynap-tic
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 empha-sizing
the importance of balancing the psychopharmacological and psychotherapeutic approaches).
Futureprogress
in the understanding and treatment of bipolar disorder will rely on successful
integration of thebiological
and psychosocial lines of investigation.Address
for correspondence: Dr Goodwin, Department of Psychiatry, George
Washington University, 2150 Pennsylvania Ave, NW, 8th Floor, Washington, DC 20037,
USA
(e-mail: psyfkg@gwumc.edu)Bipolar
disorderFrederick
K. Goodwin, MD; S. Nassir Ghaemi, MDTFrom:
the Center on Neuroscience, Medical Progress, and Society Department
of Psychiatry, George Washington University, Washington DC, USA (Dr Goodwin);
and the Department of Psychiatry, Harvard Bipolar Research Program, Massachusetts
General Hospital, Harvard Medical School, Cambridge, Mass, USA (Dr Ghaemi)4 1Frederick
K. GOODWIN
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