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Clinical differences between bipolar and unipolar depression

  • Liz Forty (a1), Daniel Smith (a1), Lisa Jones (a2), Ian Jones (a1), Sian Caesar (a2), Carly Cooper (a2), Christine Fraser (a1), Katherine Gordon-Smith (a1), Sally Hyde (a2), Anne Farmer (a3), Peter McGuffin (a3) and Nick Craddock (a4)...

Summary

It is commonly – but wrongly – assumed that there are no important differences between the clinical presentations of major depressive disorder and bipolar depression. Here we compare clinical course variables and depressive symptom profiles in a large sample of individuals with major depressive disorder (n=593) and bipolar disorder (n=443). Clinical characteristics associated with a bipolar course included the presence of psychosis, diurnal mood variation and hypersomnia during depressive episodes, and a greater number of shorter depressive episodes. Such features should alert a clinician to a possible bipolar course. This is important because optimal management is not the same for bipolar and unipolar depression.

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Copyright

Corresponding author

Professor Nick Craddock, Department of Psychological Medicine, Henry Wellcome Building, Wales School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. Email: craddockn@cf.ac.uk

Footnotes

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Declaration of interest

Funding from the Wellcome Trust, the UK Medical Research Council and GlaxoSmithKline.

Footnotes

References

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1 Sharma, V, Khan, M, Smith, A. A closer look at treament resistant depression: is it due to a bipolar diathesis? J Affect Disord 2005; 84: 251–7.
2 Beck, A, Steer, R. The Beck Depression Inventory. Harcourt Brace, 1987.
3 Wing, J, Babor, M, Brugha, T, Burke, J, Cooper, J, Giel, R, Jablenski, A, Regier, D. SCAN: Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry 1990; 47: 589–93.
4 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). APA, 1994.
5 McGuffin, P, Farmer, A, Harvey, I. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 1991; 48: 764–70.
6 Craddock, M, Asherson, P, Owen, MJ, Williams, J, McGuffin, P, Farmer, AE. Concurrent validity of the OPCRIT diagnostic system. Comparison of OPCRIT diagnoses with consensus best-estimate lifetime diagnoses. Br J Psychiatry 1996; 169: 5863.
7 Bowden, CL. A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord 2005; 84: 117–25.
8 Swann, AC, Geller, B, Post, RM, Altshuler, L, Chang, KD, Delbello, MP, Reist, C, Juster, IA. Practical clues to early recognition of bipolar disorder: a primary care approach. Prim Care Companion J Clin Psychiatry 2005; 7: 1521.
9 Mitchell, PB, Wilhelm, K, Parker, G, Austin, MP, Rutgers, P, Malhi, GS. The clinical features of bipolar depression: a comparison with matched major depressive disorder patients. J Clin Psychiatry 2001; 62: 212–16.
10 National Institute for Health and Clinical Excellence. The Management of Bipolar Disorder in Adults, Children and Adolescents, in Primary and Secondary Care. Clinical Guideline 38. NICE, 2006.
11 Angst, J. The bipolar spectrum. Br J Psychiatry 2007; 190: 189–91.

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Clinical differences between bipolar and unipolar depression

  • Liz Forty (a1), Daniel Smith (a1), Lisa Jones (a2), Ian Jones (a1), Sian Caesar (a2), Carly Cooper (a2), Christine Fraser (a1), Katherine Gordon-Smith (a1), Sally Hyde (a2), Anne Farmer (a3), Peter McGuffin (a3) and Nick Craddock (a4)...
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eLetters

Re: Symptoms do not helpfully distinguish unipolar and bipolar depression

Nick Craddock, Professor of Psychiatry
27 August 2008

We are in full agreement with Carroll about the limited utility of clinical symptoms for “diagnostic tests” and the consequent importance of efforts to discover biomarkers, endophenotypes or genetic markers. In fact, the main focus of our research is molecular genetic epidemiological investigation of mood disorders and psychoses that has precisely this aim (1-4). Further, we have a keen interest in using findings to provide biological validators for psychiatric nosology, classification and clinical diagnosis (5).

However, for the moment psychiatrists have to make do with the clinical tools available and be alert to diagnostic clues that can help inthe delivery of optimal care to their patients. We stand by the statementsin our paper: “It is commonly, but wrongly, assumed that there are no important differences in the clinical presentation of unipolar and bipolardepression... The clinical features of depression are not, of course, a definitive guide to diagnosis but can help alert the clinician to a possible bipolar course... This is important because optimal management varies between bipolar and unipolar depression.”

Declaration of interest: None.

Liz Forty a,b, Daniel Smith a, Lisa Jones b, Ian Jones a, b, Sian Caesar b, Carly Cooper b, Christine Fraser a, Katherine Gordon-Smith a, b,Sally Hyde b, Anne Farmer c, Peter McGuffin c, Nick Craddock a, b*.

a Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK.b Department of Psychiatry, Division of Neuroscience, University of Birmingham, Birmingham, UK.c MRC SGDP Research Centre, Institute of Psychiatry, London, UK.

References

1.Green E, Raybould R, McGregor S, et al, (2005) The schizophrenia susceptibility gene, Neuregulin 1 (NRG1) operates across traditional diagnostic boundaries to increase risk for bipolar disorder. Archives of General Psychiatry 62(6): 642-6.

2.Williams NM, Green E, Macgregor S, et al. (2006) Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. Arch Gen Psychiatry 63: 366-373.

3.Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007; 447:661-78.

4.Craddock N, Jones L, Jones IR et al. Strong genetic evidence for aselective influence of GABAA receptors on a component of the bipolar disorder phenotype. Molecular Psychiatry. 2008. advance online publication, 1 July 2008; doi:10.1038/mp.2008.66

5.Craddock N, Owen MJ. Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry. 2007 Jun;6(2):84-91.
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Conflict of interest: None Declared

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Symptoms do not helpfully distinguish unipolar and bipolar depression

Bernard J. Carroll, psychiatry
11 June 2008

8 June, 2008

LETTER TO EDITOR, BRITISH JOURNAL OF PSYCHIATRY

Word count 339. References 1.

In response to Forty L, Smith D, Jones L, Jones I, Caesar S, Cooper C, Fraser C, Gordon-Smith K, Hyde S, Farmer A, McGuffin P, Craddock N. Clinical differences between bipolar and unipolar depression. British Journal of Psychiatry 2008; 192: 388-389.1

This study1 revisits a familiar question and reports some statistically significant differences in the frequency of clinical features between unipolar and bipolar depressions. The report then moves beyond description to emphasize the clinical importance of these differences. The 3 symptoms most predictive of bipolar depression were presence of psychosis, diurnal mood variation, and hypersomnia. To be considered important, these symptoms when present would need to influence clinical decisions.

The sensitivity of these 3 symptoms for bipolar depression ranged from 0.3 to 0.59. The specificity ranged from 0.5 to 0.9. The positive predictive value (PPV) ranged from 0.55 to 0.69. As the prevalence of bipolar disorder in the sample was 0.43, these PPV results do not greatly increase the probability of bipolar disorder above the base rate. Likewise, the negative predictive value ranged from 0.63 to 0.69, while the base rate of unipolar depression was 0.57. Again, there is little gainof information.

Because this differential diagnosis relies on pattern recognition rather than on discrete, pathognomonic symptoms, it may be more helpful toexamine cases in which all 3 “important clinical differences” were present. When all 3 features are required, beginning with the highest PPV (psychotic features), then the middle PPV (hypersomnia), then the lowest PPV (diurnal variation), and assuming the 3 symptoms are independent, then34 bipolar cases and 7 unipolar cases would stand out. From this result, the sensitivity of the triune pattern would be 0.08 and the specificity 0.99. The PPV is 0.83 and the negative predictive value is 0.59. How “important” is a clinical symptom pattern that detects only 8% of bona fide bipolar cases and that does not positively rule in unipolar cases? Moreover, there is no guarantee that latent bipolar depression has the same symptom profile as fully expressed bipolar depression.

All in all, these results underscore the limitations of parsing clinical symptoms for the purpose of classification. The “important clinical differences” give little added information to clinicians for treatment planning. That is why efforts continue to discover biomarkers orendophenotypes or genetic markers.

Reference

Forty L, Smith D, Jones L, Jones I, Caesar S, Cooper C, Fraser C, Gordon-Smith K, Hyde S, Farmer A, McGuffin P, Craddock N. Clinical differences between bipolar and unipolar depression. British Journal of Psychiatry 2008; 192: 388-389.

Bernard J. Carroll, MBBS, PhD, FRCPsychPacific Behavioral Research FoundationP.O. Box 223040Carmel, CA 93922-3040

Phone 831-626-1467Fax 831-626-6963E-mail bcarroll@redshift.com

Courier deliveries:100 Del Mesa CarmelCarmel, CA 93923-7950
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Conflict of interest: None Declared

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