Guest Editorial

Highlighting Bipolar II Disorder

Gordon Parker, MD, PhD, DSc, FRANZCP¹

Until recently, epidemiologic studies put the lifetime risk of manic-depressive illness, or bipolar disorder (BD), at 1% to 2%. Now many clinicians are observing a considerable increase in bipolar II disorder (BD II), though in the absence of any concomitant increase in bipolar I disorder (BD I) referrals. If such observations are valid, how can they be explained? In this section several key issues are pursued (1,2). First, has there been a true increase in BD II, or has detection merely improved? Second, considering the lengthy delays between onset and diagnosis of BD II, what strategies might further improve detection? Third, how should BD I and BD II be best modelled and distinguished—along a continuum or as distinct entities? Fourth, what neurobiological processes underpin BD II, and do they differ from those underpinning BD I? Fifth, might the management of BD II require different strategies than the current armamentarium used for managing BD I, whether these disorders differ dimensionally or categorically? As clinical observation is clearly open to numerous biases, is there more formalized evidence indicating that BD may be increasing? If this is a true phenomenon, an increased incidence in community studies would be anticipated over time; There is evidence for such an increase, at least in the overall bipolar class. When we compare the lifetime rate of mania in the 1984 Epidemiological Catchment Area (ECA) Community Study (3) and in the 1994 National Comorbidity Survey (4), respective rates (that is, 0.9% and 1.6%) suggest a doubling over the decade. Additionally, if BD is increasing, we would expect a cohort effect (for example, higher rates in younger people). Turning again to ECA data, we find that the rates for those aged 18 to 24 years were 1.3%, compared with 1.6% for those aged 25 to 44 years, 0.4% for those aged 45 to 64 years, and 0.1% for those aged 65 years or over. Such data support but do not prove a change in prevalence. Alternatively, changed rates might simply reflect changes in diagnostic approaches. As detailed by Hadjipavlou and colleagues (2), the application of hard and soft diagnostic criteria in a Zurich study is illuminating (5). In that cohort, the rates for BD I were 0.5% and 0.5% for “hard” and “soft” diagnostic assignment, respectively, and were identical to the DSM-IV decision rule-assigned rate. For BD II, the prevalence rate was 5.3% for hard diagnostic assessment and 11.9% for soft diagnostic assignment, with both well exceeding the DSM-IV rate of 1.6%. Study results indicate that the impact of differing assessment methods is more likely to apply to BD II than to BD I and that DSM-IV rates tend to be lower than clinician- driven rates. Such differences are likely to be distinctly influenced by the DSM-IV requirement that a hypomanic state last at least 4 days. Other artefactual determinants of higher prevalence estimates include a widening of the definition of BD. The old diagnostic label of manic-depressive psychosis was rarely applied and is logically inappropriate in instances of milder bipolar states. As we are now seeing a broader subsection of the population, the rates of those with BD II may not necessarily correspond with those coming to clinical attention before and after mood disorder destigmatization. Again, redefinition or reconceptualization of certain diagnostic categories (for example, cyclothymia) has effectively broadened the spectrum of BDs. If there has been a real increase in BD II, a wide set of possible determinants invite speculation. Genetic changes would need to be considered. Environmental influences include increased use of illicit stimulant drugs and even increased use of prescribed antidepressants, because of their suggested capacity to cause “switching.” Another environmental candidate intriguing our research team is an omega-3 fatty acid (O3FA) contribution with several indirect lines of evidence. Several studies have shown striking associations (with correlations exceeding 0.8) between fish consumption and cross-national rates of both major depression (6) and postpartum depression (7). Certain O3FAs have mood-stabilizing (8) and antidepressant- augmenting (9,10) properties, while deficient O3FA levels have been demonstrated in patients with depression (11,12). How do we improve accurate identification? Clearly, all individuals with a depressive condition should be screened for features of manic or hypomanic episodes. Questions may reflect DSM-IV criteria or other approaches. Our Web site (see www.blackdoginstitute.org.au) has an 18-item bipolar screening measure that clinicians can use as a self-report to shape questions or to assist diagnostic clarification. However, as Hadjipavlou and colleagues noted, a negative screen can fail to detect persons with BD II who are otherwise identified by careful clinical interview (2). The chance of a valid diagnosis of BD II is increased by obtaining a positive family history, historical evidence of a defined onset (though we now recognize that onset can occur in young children), and sometimes by interview of a corroborative witness. Thus the suggestion that observed hypomanic behaviour should be an obligatory diagnostic component (2) might decrease the false-positive rate, but it would also compromise sensitivity by excluding many persons with true BD II. While the DSM-IV imposes minimum durations of at least 1 week for BD I and at least 4 days for BD II, we do not find these to be necessarily valid in clinical practice, as many individuals with clear-cut BD report “highs” lasting only 1 or 2 days or even hours. It is of more than theoretical importance to determine whether BD I and BD II are best modelled along a continuum of severity and (or) another feature or as representing differing categorical entities. If the former is operative, we might anticipate similar etiologic factors and a similar management armamentarium. In the latter model, differing (albeit overlapping) causes might be assumed, while management might involve disorder-specific strategies. The centrality of the issue is taken up in the contributing articles. Hadjipavlou and colleagues offer a succinct and informative overview of the bipolar spectrum and note the risk of expanding the spectrum to one too many hues (2). There is an argument, then, for first distinguishing BD I and BD II before climbing the spectrum mountain. The article by McGrath and colleagues is therefore of deceptive importance in its review of studies involving several neurobiological markers to determine whether differences exist between BD I and BD II (1). The overall pattern argues against substantive differences. Whether this offers indirect support for a dimensional model, whether subjects with BD I and BD II subjects were adequately distinguished in such studies, or whether the slight differences reflect the few (and often underpowered) studies are key points that emerge from this important overview. If psychotic features are ignored for the moment, our analyses indicate that nearly all the key nonpsychotic symptoms of mania and hypomania appear to conform to a dimensional model. Any categorical distinction may then be restricted to the presence or absence of psychotic features, which is akin to distinctions between melancholic and psychotic depression, where debate has long continued regarding whether these conditions are separate or aligned on a severity continuum. There is a need to consider the utility of a similar hierarchical or recruitment model, where the “high” is the central shared component (underpinned by certain biological processes), while the “add-on” psychotic features are determined by additional biological perturbations. This option might regard all nonpsychotic “high” states as hypomania and, if they are consistently so longitudinally, call these conditions BD II, while preserving the term mania for psychotic states and the diagnosis of BD I for psychotic manic states. Such a 2-tiered model for the BDs (as with psychotic and melancholic depression) would anticipate differential treatment effects. There is now a wide range of established and experimental treatments available for the management of BD I, including mood stabilizers, atypical antipsychotics, and complementary psychotherapies (13). Whether these treatments have the same relevance to BD II is unclear; one example should suffice. It is commonly suggested that, in managing bipolar depression, antidepressants are contraindicated because they can cause switching to manic states. However, a review of the literature suggests that those with BD do not appear at any greater risk of having a manic episode induced by the prescription of a selective serotonin reuptake inhibitor (SSRI) or dual-action antidepressant (14), which is in line with Hadjipavlou and colleagues’ interpretation (2). Further, numerous BD II patients, when commenced on SSRIs and dual-action drugs, not only report an improvement in their depression but also a decreased number of “highs” and a decrease in the duration and severity of “highs,” allowing the hypothesis that such antidepressants may have mood stabilizing properties for those with BD II (15). If validated, such an approach might well be an initial treatment regime, while current standard strategies for managing BD I might then be secondary or subsequent options for BD II patients. As noted by Hadjipavlou and colleagues, basing treatment recommendations on studies of BD I “may prove to be at the very least hasty and premature, if not inappropriate” (2). My only caveat to their comprehensive overview is in regard to their recommendation to initiate treatment for BD II with lamotrogine or lithium. While they provide supportive data from a study by Calabrese and other distinguished colleagues, lamotrogine can be a demanding drug to use, and it might be preferable to await replication studies before viewing this as a first-line therapy. Hadjipavlou and colleagues provide us with a clear message (2). While many view BD II as a mild condition (or even as lacking disorder status), their review of a comprehensive set of clinical course studies indicates that, while the hypomanic episodes may not be necessarily disabling, the depressive episodes are perhaps just as disabling as they are for persons with BD I. The enervating biological features, in conjunction with the manic or hypomanic episodes, support the clinical diagnosis and make the study of BD II a highly meaningful endeavor. True BD II is a substantively disabling condition, and sufferers will benefit from highlighting the need for continuing high-level research and close clinical observation of treatment differentiation. References 1. McGrath BM, Wessels P, Bell EC, Ulrich M, Silverstone PH. Neurobiological findings in bipolar II disorder compared with those in bipolar I disorder. Can J Psychiatry 2004;49:794–801. 2. Hadjipavlou G, Mok H, Yatham LN. Bipolar II disorder: an overview of recent developments. Can J Psychiatry 2004;49:802–12 3. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Regier DA. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984;41:949–58. 4. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, and others. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19. 5. Angst J. The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50:143–51. 6. Hibbeln JR. Fish consumption and major depression. Lancet 1998;351:1213. 7. Hibbeln JR. Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2001;69:15–29. 8. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, and others. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind placebo-controlled trial. Arch Gen Psychiatry 1999;56:407–12. 9. Nemets B, Stahl Z, Belmaker RH. Addition of Omega-3 Fatty Acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 2002;159:477–9. 10. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with depression despite adequate treatment with standard drugs. Arch Gen Psychiatry 2002;59:913–9. 11. Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149–55. 12. Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY. Lowered Omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275–91. 13. Lam DH, Watkins ER, Hayward P, Bright J, Wright K, Kerr N, and others. A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year. Arch Gen Psychiatry 2003;60:145–52. 14. Parker G, Parker K. Which antidepressants flick the switch? A review. Aust N Z J Psychiatry 2003;37:464–8. 15. Parker G. Do the newer antidepressants have mood stabilizing properties? [letter]. Aust N Z J Psychiatry 2002;36:427–8. Author(s) 1 Scientia Professor, School of Psychiatry, University of New South Wales, Sydney, Australia; Executive Director, Black Dog Institute, Sydney, Australia. Address for correspondence: Dr G Parker, Black Dog Institute, Prince of Wales Hospital, Randwick 2031, Sydney, Australia. e-mail: G.Parker@unsw.edu.au