Bipolar II Disorder: Reasons to Recognize

Bipolar II Disorder: Reasons to Recognize

William H. Coryell, MD

Over 40 years ago, clinical observations generated proposals for a distinction among mood-disordered patients between those who experience mania in the course of their illness and those who experience only hypomania.1 Concerns that this distinction could not be made reliably delayed its inclusion in official nomenclature until DSM-IV appeared 25 years later. The availability of other operational definitions and, in particular, the Research Diagnostic Criteria,2 nevertheless fostered an accumulation of findings in support of bipolar II disorder as a valid category. The JCP article by Frankland et al3 is among the most recent of these and is one of the few that have compared symptom profiles of major depressive disorder (MDD) to those of bipolar I depression and bipolar II depression separately. Both of the bipolar depression groups differed from the MDD group in nonoverlapping ways. Thus, contrasts in depressive symptom composition can be added to the other lines of evidence that bipolar I and bipolar II disorders differ.

The strongest support for the separation lies in family studies. At least 7 show that bipolar II disorder is more prevalent among the relatives of bipolar II probands than among those of bipolar I probands and, conversely, that bipolar I disorder is more prevalent among the relatives of bipolar I probands.4-10 A prospective component of that study also showed that patients who switch from MDD to bipolar II disorder are more likely to have bipolar II relatives, while those who switch to bipolar I disorder instead have a preponderance of bipolar I relatives.11

Although measures of diagnostic stability are rare, their results can provide robust evidence for validity. Only a few reports have described the likelihood of shifts from bipolar II to bipolar I disorder, but those that have found that this happens in only 5%10 and 7.5%12 of adult samples. A higher rate of 25% reported by the Course and Outcome of Bipolar Youth study13 suggests that diagnostic stability may be lower in child and adolescent populations.

Follow-up studies have also revealed differences between the courses of bipolar I and bipolar II disorder, though with less consistency. Some have found that patients with bipolar II disorder experience more depressive morbidity, less time in elevated mood states, more comorbidity, a greater likelihood of suicide attempts, and more psychological impairment.14 A particularly interesting difference between groups is in the likelihood of seasonal patterns. Seasonality among bipolar patients appears to be either confined to,15 or much more prevalent in,16,17 bipolar II groups. Individuals with bipolar II disorder thus may be more photosensitive, and those with bipolar II depression might therefore derive more benefit from light therapy than those with bipolar I depression. Although bipolar depression, with or without seasonal patterns, is often more responsive to phototherapy than is MDD,18 there seems to be no equivalent comparison between bipolar I and bipolar II depression in responsiveness to light therapy.

Only a few genomic studies have separated bipolar I disorder from bipolar II disorder, but there are indications that doing so may be very worthwhile. In one, sibling pairs concordant for bipolar II disorder characterized families with evidence of linkage to 18q but not families that did not show linkage.19 More recently, a genomewide association study analysis of a combined cohort revealed that genomewide significance for an association with the adrenomedullary gene on 11p was specific to bipolar II disorder.20

Support for the validity of bipolar II disorder has emerged despite the obvious difficulty of accurately diagnosing hypomania, a syndrome that is rarely current at the time of the diagnostic assessment and that shades into normal periods of excitement or elation. In addition, the boundary between mania and hypomania is largely based on duration, on the need for hospitalization, or on the degree of resulting impairment rather than on symptom number and type.

The evidence stands, though, and clearly argues for efforts to characterize how the bipolar I/bipolar II dichotomy might bear usefully on treatment selection. Unfortunately, most large-scale treatment studies are industry sponsored and are designed to achieve an indication for a particular disorder, very rarely for its subtypes. So far, psychiatric drug effects more often generalize across disorders than show specificity to a subtype. Support for the bipolar I/bipolar II distinction seems stronger than that for most other subtypes in psychiatric nosology, though, and therefore may prove a more useful tool for tailoring treatment.

Author affiliations: Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City.

Potential conflicts of interest: None reported.

Funding/support: None reported.

REFERENCES

1. Dunner D. A review of the diagnostic status of “Bipolar II” for the DSM-IV Work Group on Mood Disorders. Depression. 1993;1(1):2-10. doi:10.1002/depr.3050010103

2. Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders. 3rd ed. New York, NY: Biomedical Research; 1978.

3. Frankland A, Cerrillo E, Hadzi-Pavlovic D, et al. Comparing the phenomenology of depressive episodes in bipolar I and II disorder and major depressive disorder within bipolar disorder pedigrees. J Clin Psychiatry. 2015;76(1):32-39. doi:10.4088/JCP.14m09293.

4. Heun R, Maier W. The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: results of a controlled family study. Acta Psychiatr Scand. 1993;87(4):279-284. PubMed doi:10.1111/j.1600-0447.1993.tb03372.x

5. Gershon ES, Hamovit J, Guroff JJ, et al. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry. 1982;39(10):1157-1167. PubMed doi:10.1001/archpsyc.1982.04290100031006

6. Fieve RR, Go R, Dunner DL, et al. Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders. J Psychiatr Res. 1984;18(4):425-445. PubMed doi:10.1016/0022-3956(84)90031-1

7. Coryell W, Endicott J, Reich T, et al. A family study of bipolar II disorder. Br J Psychiatry. 1984;145(1):49-54. PubMed doi:10.1192/bjp.145.1.49

8. Simpson SG, Folstein SE, Meyers DA, et al. Bipolar II: the most common bipolar phenotype? Am J Psychiatry. 1993;150(6):901-903. PubMed

9. Merikangas KR, Cui L, Heaton L, et al. Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders. Mol Psychiatry. 2014;19(2):214-219. PubMed doi:10.1038/mp.2013.116

10. Joyce PR, Doughty CJ, Wells JE, et al. Affective disorders in the first-degree relatives of bipolar probands: results from the South Island Bipolar Study. Compr Psychiatry. 2004;45(3):168-174. PubMed doi:10.1016/j.comppsych.2004.02.005

11. Fiedorowicz JG, Solomon DA, Endicott J, et al. Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosom Med. 2009;71(6):598-606. PubMed doi:10.1097/PSY.0b013e3181acee26

12. Coryell W, Endicott J, Maser JD, et al. Long-term stability of polarity distinctions in the affective disorders. Am J Psychiatry. 1995;152(3):385-390. PubMed

13. Birmaher B, Axelson D, Goldstein B, et al. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009;166(7):795-804. PubMed doi:10.1176/appi.ajp.2009.08101569

14. Angst J, Gamma A, Bowden CL, et al. Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity. Eur Arch Psychiatry Clin Neurosci. 2013;263(8):663-673. PubMed doi:10.1007/s00406-013-0393-4

15. Friedman E, Gyulai L, Bhargava M, et al. Seasonal changes in clinical status in bipolar disorder: a prospective study in 1000 STEP-BD patients. Acta Psychiatr Scand. 2006;113(6):510-517. PubMed doi:10.1111/j.1600-0447.2005.00701.x

16. Goikolea JM, Colom F, Martí­nez-Arán A, et al. Clinical and prognostic implications of seasonal pattern in bipolar disorder: a 10-year follow-up of 302 patients. Psychol Med. 2007;37(11):1595-1599. PubMed

17. Rosenthal NE, Sack DA, Gillin JC, et al. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry. 1984;41(1):72-80. PubMed doi:10.1001/archpsyc.1984.01790120076010

18. Deltito JA, Moline M, Pollak C, et al. Effects of phototherapy on non-seasonal unipolar and bipolar depressive spectrum disorders. J Affect Disord. 1991;23(4):231-237. PubMed doi:10.1016/0165-0327(91)90105-2

19. McMahon FJ, Simpson SG, McInnis MG, et al. Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder. Arch Gen Psychiatry. 2001;58(11):1025-1031. PubMed doi:10.1001/archpsyc.58.11.1025

20. Huang J, Perlis RH, Lee PH, et al. Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression. Am J Psychiatry. 2010;167(10):1254-1263. PubMed doi:10.1176/appi.ajp.2010.09091335