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SHORT COMMUNI CATI ON Open Access Bipolar disorders in DSM-5: strengths, problems and perspectives Jules Angst Abstract The diagnostic classification of mood disorders by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) had two major shortcomings: an underdiagnosis of bipolar disorders and a large proportion of treated patients had to be allocated to the vague NOS groups ‘not otherwise specified’. Several new subthreshold groups of depression, bipolar disorders and mixed
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  SHORT COMMUNICATION Open Access Bipolar disorders in DSM-5: strengths,problems and perspectives Jules Angst Abstract  The diagnostic classification of mood disorders by the  Diagnostic and Statistical Manual of Mental Disorders  (DSM-IV-TR)had two major shortcomings: an underdiagnosis of bipolar disorders and a large proportion of treated patients had tobe allocated to the vague NOS groups  ‘ not otherwise specified ’ . Several new subthreshold groups of depression,bipolar disorders and mixed states are now operationally defined in DSM-5. In addition, hypomanic and manicepisodes occurring during antidepressant treatments are, under certain conditions, accepted as criteria for bipolardisorders. The diagnosis of bipolarity now requires, as entry criterion A, not only the presence of elated or irritablemood but also the association of these symptoms with increased energy/activity. This restriction will unfortunatelychange the diagnoses of some patients from DSM-IV bipolar I and II disorders to subdiagnostic bipolar syndromes.Nonetheless, overall, DSM-5 is a step in the right direction, specifying more subdiagnostic categories with an improveddimensional approach to severity. DSM-5 may also have an impact on patient selection for placebo-controlled drugtrials with antidepressants. Introduction The strength of the  Diagnostic and Statistical Manual of   Mental Disorders  (DSM-III, DSM-III-R and DSM-IV)was to base psychiatric diagnoses on defined operationalcriteria, which resulted in high inter-rater reliability. Aweakness, shown in relation to DSM-IV, was  that it wasonly able to formally diagnose under half the patientsactually treated   (Angst et al. 2010). This clinically un-acceptable situation was derived partly from the lack of operationalized subthreshold diagnoses. Now, in recogni-tion of the fact that for a large group of patients receivingtreatment doctors often had no alternative to the residual,catch-all diagnosis not otherwise specified (NOS), DSM-5includes defined subthreshold syndromes, which will alsostimulate research and allow a more dimensional view.For depression, for example, recurrent brief depressionand even short-duration depressive episodes (4 to 13days), as well as 2-week episodes with insufficient symp-toms, now have their place. Bipolar disorders in DSM-5 The main lines of the DSM-5 definition of major depres-sive episodes (MDE), basic to the diagnoses of bothbipolar I and bipolar II disorders, are similar to those of DSM-IV: presence of five of nine diagnostic symptomswith a minimum duration of 2 weeks and a change fromprevious functioning. However, it is now possible to spe-cify both depressive disorders and bipolar disorders withmixed features.The definitions of both manic and hypomanic episodeshave been radically revised, which will impact on both bi-polar diagnoses. The main changes are three: (1) a prob-lematic change concerning the gate questions (criterionA), (2) a welcome reduction in the number of exclusioncriteria and (3) a vigorous effort to operationalize bipolarsubthreshold syndromes, hitherto unified under the NOSheading. Gate questions for mania and hypomania Where DSM-IV required, as criterion A, the presence of one of the two mood symptoms (elation/euphoric or ir-ritable mood), in DSM-5,  ‘ the mood change must be ac-companied by persistently increased activity or energy levels ’ . This new rule is, of course, more restrictive andexcludes all individuals who report only one of the threeentry symptoms and those with both elated and irritablemood. Thus, for no apparent reason, DSM-5 classifiessome patients as having subthreshold bipolar disorderswho would formerly have been diagnosed with manic Correspondence: jules.angst@uzh.chResearch Department, Zurich University Psychiatric Hospital, Lenggstrasse 31,Zurich 8032, Switzerland © 2013 Angst; licensee Springer. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproductionin any medium, provided the srcinal work is properly cited. Angst  International Journal of Bipolar Disorders  2013,  1 :12http://www.journalbipolardisorders.com/content/1/1/12  episodes or bipolar I or II disorders. This strict new ruleis not based on data, indeed it contradicts available evi-dence. As the international Bridge Study of 5,635 pa-tients seeking treatment for major depressive episodesdemonstrated clearly, any of those three gate questionsis valid on its own, according to the criteria establishedby Robins and Guze (1970) and Angst et al. (2012). Exclusion criteria One important and amply justified change in DSM-5concerns the diagnosis of bipolar II disorder. InDSM-IV, the change of major depression into  hypo-mania under antidepressant treatments  (ADs) was inprinciple an exclusion criterion. In DSM-5, that change -provided it persists at fully syndromal level beyond thephysiological effect of the treatment - is explicitly a cri-terion for bipolar II disorder. DSM-5, like DSM-IV,allows some scope for clinical judgment as to causality.In addition, DSM-5 provides new formal criteria for sub-stance/medication-induced bipolar and related disorder.On the basis of the Bridge Study data (Angst et al.2012), we can estimate that DSM-5 bipolar II disorderwill be diagnosed about twice as often as heretofore andhave a prevalence approaching that of bipolar I.A more frequent diagnosis of bipolar II disorder isboth justified and logical: a milder condition (in this casehypomania) is usually more prevalent than a severe one(mania). Over the long-term course of their illness, bipo-lar patients spend much more time in milder conditions,mainly minor depression, than in major syndromes(Phillips and Kupfer 2013).Two exclusion criteria survive in DSM-5, namely   ‘ sub-stance/medication-induced bipolar and related disorder ’  and ‘ bipolar and related disorder due to another medical condi-tion ’ . Both clearly rely on questionable causal attributionsbased on partial co-occurrence with substance or medicationuse or full co-occurrence with another medical condition. Other specified bipolar and related disorder (DSM-5) DSM-5 has fortunately replaced DSM-IV's vague groupNOS by defining MDE with several subthreshold conditionsof bipolarity, for instance, allowing a duration of 2 to 3 daysfor hypomanic episodes, as suggested by child psychiatrists,or fewer than four symptoms of hypomania during 4 days,or, for cyclothymia, specifying shorter manifestations (<24months). A further important step is the recognition thatdysthymia can co-occur with hypomania which is consid-ered as a co-morbid condition, but why - one might ask - isit not allocated to cyclothymic disorder? Underdiagnosis of bipolar disorders, hypomaniaand mania The underrecognition of bipolar disorder is sadly set tocontinue despite the advances of DSM-5 describedabove. The re-analyses of large epidemiological studiesdemonstrated that DSM major depressive disorder(MDD) is clearly heterogenous and includes about 40%of hidden bipolars. Without systematic screening forhypomania in patients' previous history, DSM-5 willhave little appreciable impact on the detection of thishidden bipolarity. The vast majority of patients withMDE will continue to be diagnosed as having MDD.In this context, DSM-5's (and ICD's) non-recognitionof pure mania and hypomania as diagnostic entities re-mains problematic in view of the accumulating evidence.Both conditions are fairly common in adolescence(Päären et al. 2013). Moreover, the large, representative,epidemiological NCS-A study (  N   = 10,123 adolescentsaged 13 to 18 years) has demonstrated the frequent in-dependence of mania and hypomania from depression(Merikangas et al. 2012). Most recently, the NIMH fam-ily study of patients with mood disorders has shown thatmania is even genetically independent (Merikangaset al., in press). Adolescents, unlike adults, more oftenmeet the DSM-IV criteria for mania and hypomaniawithout MDD than for bipolar disorders, but they areoften unaware of their mood changes, whereas adults'retrospective assessments are rich in false negatives, asMoffitt et al. (2010) have recently demonstrated in rela-tion to major depressive episodes.With the predicted continuing underdiagnosis of bipo-lar disorder, the underprescription of lithium, its bestestablished prophylactic treatment, is also likely to per-sist. Lithium reduces suicides, improves the course of the illness and may even lower the risk of dementia inthese patients (Angst et al. 2007; Nunes et al. 2007; Kessing et al. 2008), whose risk of dementia is elevated(da Silva et al. 2013). Recommendations for trials with antidepressants Non-response to ADs in MDD is correlated with hiddenbipolarity (Hantouche et al. 2009; Rybakowski et al.2010; Correa et al. 2012). Systematic screening for hypo- manic symptoms during the selection of patients forcontrolled antidepressant trials would have several bene-fits. It would identify bipolarity in patients with majordepressive episodes and increase the homogeneity of thesamples, increase the responder rates and the power of placebo-controlled trials, and finally reduce the samplesizes required. Systematic measures of hypomanic symp-toms by rating scales during the trials would help toidentify the development of mixed states and switchesinto hypomania. Future directions in research on the bipolarspectrum As I see it, future research should focus on the independ-ence of mania and hypomania from bipolar disorder, and Angst  International Journal of Bipolar Disorders  2013,  1 :12 Page 2 of 3http://www.journalbipolardisorders.com/content/1/1/12  the unsolved issue in adolescent psychiatry of whetherhyperthymic behaviour in some adolescents remainswithin the normal range of variation of emotional devel-opment or emotional dysregulation (Päären et al. 2013).This developmental phase is strongly associated with thestart of substance misuse (tobacco, alcohol and drugs),which may be secondary to normal adolescent  ‘ highs ’  orto early hypomanic episodes, as suggested by the results of the NCS-A study (see also review of Post and Kalivas2013). Adolescents therefore pose a special difficulty - thatof distinguishing between developmental trait/tempera-ment (hyperthymia) and states (hypomanic or mixed epi-sodes). The traditional criteria for caseness, such asdistress or impairment, are not applicable to typical syn-dromes of hypomania and mania since the subjects do notfeel in any way ill or impaired. In most cases, the only con-clusive basis for diagnosing undesired social consequencesmay be the information provided by parents, friends,teachers or employers.Another topic requiring further research is the dur-ation criteria for MDE (2 weeks) and for hypomania(4 days), the validity if which has been questioned by re-cent data from the Bridge and the Zurich studies (Angstet al. 2012). In principle, all continuous variables, suchas distress/suffering, impairment, episode duration andtime spent in illness over 1 year (2 years for a chronicsyndrome), should be measured systematically in clinicalassessments and not just dichotomized for diagnosticdefinitions.Structured diagnostic interviews for clinical and epi-demiological purposes should include all subthresholdcategories ( ‘ other specified diagnostic categories 311 ’ (F32.8) and  ‘ other specified bipolar and related disorder ’ 296.89 (F31.89). This can provide the necessary data forfuture revisions.Urgently needed, but underfunded, are methodologic-ally sound prospective studies of patient and community samples, taking both somatic and psychiatric aspects of health and illness equally into account. Here, the new DSM-5 will certainly help, but it would be short-sighted torestrict data collection to current diagnostic concepts,which will have a short half-life of 10 years or less. Otherperspectives for future biological research on the spectrumof unipolar depression and bipolar disorder have beenoutlined by Phillips and Kupfer (2013). Competing interests  The author declares that he has no competing interests. Received: 14 June 2013 Accepted: 3 July 2013Published: 23 August 2013 References Angst J, Gamma A, Gerber-Werder R, Zarate CA Jr, Manji HK.  Does long-termmedication with lithium, clozapine or antidepressants prevent orattenuate dementia in bipolar and depressed patients?  Int J Psychiatr ClinPract.  2007;  11: 2 – 8.Angst J, Gamma A, Clarke D, Ajdacic-Gross V, Rössler W, Regier D.  Subjectivedistress predicts treatment seeking for depression, bipolar, anxiety, panic,neurasthenia and insomnia severity spectra.  Acta Psychiatr Scand.  2010; 122: 488 – 98.Angst J, Gamma A, Bowden CL, Azorin JM, Perugi G, Vieta E, Young AH. Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes.  Eur Arch Psychiatry Clin Neurosci.  2012;  262: 3 – 11.Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S.  Isunrecognized bipolar disorder a frequent contributor to apparenttreatment resistant depression?  J Affect Disord.  2012;  127: 10 – 8.da Silva J, Gonçalves-Pereira M, Xavier M, Mukaetova-Ladinska EB.  Affectivedisorders and risk of developing dementia: systematic review. Br J Psychiatry.  2013;  202: 177 – 86.Hantouche E, Azorin JM, Lancrenon S, Garay R-P, Angst J.  Prévalence del'hypomanie dans les dépressions majeures récurrentes ou résistantes:enquêtes Bipolact.  Ann Med Psychol.  2009;  167: 30 – 7.Kessing LV, Sondergard L, Forman JL, Andersen PK.  Lithium treatment and risk of dementia.  Arch Gen Psychiatry.  2008;  65: 1331 – 5.Merikangas KR, Cui L, Kattan G, Carlson G, Youngstrom EA, Angst J.  Mania withand without depression in a community sample of U.S. adolescents.  Arch Gen Psychiat.  2012;  69: 943 – 51.Merikangas KR, Lihong C, Heaton L, Nakamura E, Roca C, Ding J, Qin H, Yao Y,Zarate CA, Angst J.  Independence of familial transmission of mania anddepression: results of the NIMH family study of affective spectrumdisorders.  Mol Psychiatry.  2999. In press.Moffitt TE, Caspi A, Taylor A, Kokaua J, Milne BJ, Polanczyk G, Poulton R.  Howcommon are common mental disorders? Evidence that lifetimeprevalence rates are doubled by prospective versus retrospectiveascertainment.  Psychol Med.  2010;  40: 899 – 909.Nunes PV, Forlenza OV, Gattaz WF.  Lithium and risk for Alzheimer's disease inelderly patients with bipolar disorder.  Br J Psychiatry.  2007;  190: 359 – 60.Päären A, von Knorring A-L, Olsson G, Von Knorring L, Bohman H, Jonsson U. Hypomania spectrum disorders from adolescence to adulthood: a 15-yearfollow-up of a community sample.  J Affect Disord.  2013;  145: 190 – 9.Phillips ML, Kupfer DJ.  Bipolar disorder diagnosis: challenges and futuredirections.  Lancet.  2013;  381: 1663 – 71.Post RM, Kalivas P.  Bipolar disorder and substance misuse: pathological andtherapeutic implications of their comorbidity and cross-sensitisation. Br J Psychiatry.  2013;  202: 172 – 6.Robins E, Guze SB.  Establishment of diagnostic validity in psychiatric illness: itsapplication to schizophrenia.  Am J Psychiatry.  1970;  126: 983 – 7.Rybakowski JK, Angst J, Dudek D, Pawlowski T, Lojko D, Siwek M, Kiejna A.  Polishversion of the Hypomania Checklist (HCL-32) scale: the results in treatment-resistant depression.  Eur Arch Psychiat Neurol Sci.  2010;  260: 139 – 44. doi:10.1186/2194-7511-1-12 Cite this article as:  Angst:  Bipolar disorders in DSM-5: strengths,problems and perspectives.  International Journal of Bipolar Disorders 2013  1 :12. Submit your manuscript to a  journal and benefit from: 7   Convenient online submission 7   Rigorous peer review 7   Immediate publication on acceptance 7   Open access: articles freely available online 7   High visibility within the field 7   Retaining the copyright to your article   Submit your next manuscript at 7  springeropen.com Angst  International Journal of Bipolar Disorders  2013,  1 :12 Page 3 of 3http://www.journalbipolardisorders.com/content/1/1/12
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