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Editorial   |    
Redefining Bipolar Disorder: Toward DSM-V
Mary L. Phillips, M.D.; Ellen Frank, Ph.D.
Am J Psychiatry 2006;163:1135-1136. doi:10.1176/appi.ajp.163.7.1135

We now recognize that bipolar disorder is often accompanied by anxiety, eating, and substance use disorders (1) and high rates of medical illness, especially cardiovascular, cerebrovascular, and metabolic diseases (2). Individuals with bipolar disorder also suffer from a marked disruption in sleep rhythms and social relations. Rather than defining bipolar disorder solely as one of episodic mood disturbances, we should consider defining it as a multisystem disorder involving disturbances in all of the above-mentioned domains. By employing a symptom-based rather than an etiologically based approach, DSM-IV fails to reflect the multisystem presentation of bipolar disorder.

Increasingly sophisticated neuroimaging and genetic research have deepened our understanding of the neurobiology of bipolar disorder as one involving complex disturbances in relationships, linking environment, genes, neural systems, and behavior. This approach supports the research agenda for DSM-V, emphasizing the need to translate basic and clinical neuroscience research findings into a new classification system for psychiatric disorders (3). Although the understanding of the pathophysiology of bipolar disorder remains limited, preliminary findings from recent neuroimaging studies have indicated persistent dysfunctions specific to bipolar disorder within neural systems underlying mood and cognition (4, 5) that are also found in healthy first-degree relatives as endophenotypes of the disorder (6). Specific genetic variables contributing to normal functional variation may further affect dysfunctions within these systems (7).

How can DSM-V reflect the clinical complexity and pathophysiology of bipolar disorder? An immediate first step is initiating large-scale studies to identify the specific clinical spectrum, neurocognitive, and neuroimaging measures that best distinguish individuals with bipolar disorder from those with other mood and psychotic disorders and incorporating these as supplementary diagnostic criteria into DSM-V. The future challenge will be to test the construct validity of these new measures versus conventional criteria in longitudinal studies examining clinical outcome and treatment response, leading ultimately to an etiologically and pathophysiologically based classification system for bipolar disorder.

1.Frank E, Kupfer DJ, Thase ME, Mallinger AG, Swartz HA, Fagiolini AM, Grochocinski V, Houck P, Scott J, Thompson W, Monk T: Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Arch Gen Psychiatry 2005; 62:996–1004
 
2.Kupfer DJ: The increasing medical burden in bipolar disorder. JAMA 2005; 293:2528–2530
 
3.Kupfer DJ, First MB, Regier DA (eds): A Research Agenda for DSM-V. Washington, DC, American Psychiatric Association, 2002
 
4.Lawrence N, Williams A, Surguladze S, Brammer MJ, Williams SCR, Phillips ML: Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar and major depression. Biol Psychiatry 2004; 55:578–587
 
5.Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS: A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry 2003; 60:601–609
 
6.Kruger S, Alda M, Young LT, Goldapple K, Parikh S, Mayberg HS: Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. Am J Psychiatry 2006; 163:257–264
 
7.Hasler G, Drevets WC, Gould TD, Gottesman II, Manji HK: Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry Jan 6, 2006 (Epub ahead of print)
 

+From the Department of Psychiatry, University of Pittsburgh. Address correspondence and reprint requests to Dr. Phillips, Western Psychiatric Institute and Clinic, Kaufmann Building, Suite 1101, 3471 Fifth Ave., Pittsburgh, PA 15213; phillipsml@upmc.edu (e-mail).Dr. Phillips reports no competing interests. Dr. Frank wrote Treating Bipolar Disorder: A Clinician’s Guide to Interpersonal and Social Rhythm Therapy, Guilford Press, 2005; she is on the neuroscience advisory boards of Pfizer and Eli Lilly; she has served as a consultant for Servier and Novartis; and she has an investor-initiated grant on unipolar depression from Forest’s Foundation. Dr. Freedman has reviewed this editorial and found no evidence of influence from these relationships.

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References

1.Frank E, Kupfer DJ, Thase ME, Mallinger AG, Swartz HA, Fagiolini AM, Grochocinski V, Houck P, Scott J, Thompson W, Monk T: Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Arch Gen Psychiatry 2005; 62:996–1004
 
2.Kupfer DJ: The increasing medical burden in bipolar disorder. JAMA 2005; 293:2528–2530
 
3.Kupfer DJ, First MB, Regier DA (eds): A Research Agenda for DSM-V. Washington, DC, American Psychiatric Association, 2002
 
4.Lawrence N, Williams A, Surguladze S, Brammer MJ, Williams SCR, Phillips ML: Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar and major depression. Biol Psychiatry 2004; 55:578–587
 
5.Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS: A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry 2003; 60:601–609
 
6.Kruger S, Alda M, Young LT, Goldapple K, Parikh S, Mayberg HS: Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. Am J Psychiatry 2006; 163:257–264
 
7.Hasler G, Drevets WC, Gould TD, Gottesman II, Manji HK: Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry Jan 6, 2006 (Epub ahead of print)
 
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