Manic disorder as an element of the mood spectrum IRPB Lisbon, March 2015 Jules Angst, M.D. Psychiatric Hospital University of Zurich, Switzerland

History of mania and the mood spectrum Folie circulaire: Falret 1851 Manic-Depressive Disorder: Kraepelin 1899 Mania as a state of hyperfunction of nerve transmission, an independent disorder: Wernicke 1906 Bipolar vs. depressive disorder: Angst 1966, Perris 1966, Winokur, Clayton and Reich 1969 Bipolar-II disorder: Dunner, Gershon and Goodwin 1976 Affective spectrum: Akiskal 1983: Dep – BP-II – BP-I Spectrum: D – BP-II – BP-I – Md – M: Angst 1978, 1980 DSM : no Mania ICD-11: no Mania

Three-dimensional mood spectrum Angst, J et al submitted for publication

Epidemiological studies on unipolar mania (UM) and hypomania (um) EDSP Munich*: UM=1.5%, um=1.8% (follow-up over 10 years) NCS-A USA** : M/Md=1.7% (no follow-up) * Beesdo et al. 2009: Bipolar Disord 11: ** Merikangas et al. 2012: Arch Gen Psychiat 69:

Zurich Study: cumulative incidence of DSM-III-R/DSM-IV mood disorders from age 20 to 50 (Eun, J et al. Poster APPA 2015)

Major mood disorders: four groups Modified DSM-5 concept without hierarchy of energy/activity over elated and irritable mood. M/Md Mania/Mania with minor depr. dis. N=18 BP-I Bipolar-I disorder N=19 MDE/m/msx: BP-II (N=8) or MDE with manic symptoms (N=86), together N=96 MDD without manic symptoms N=102 OTHERS without minor depr. dis. or manic sx.N=174 Statistics comparing the four groups of mood disorders

Major mood disorders by gender (N) Zurich Study: modified DSM-5 concept N

Major mood disorders: % family history for mania, depression and anxiety/panic p<.03 p<.006

Major mood disorders: temperament (%) p<.0005 * p<.0001 * significant p values between M/Md and BP-I

Major mood disorders: comorbidity with abuse/dependence (%) p<.003 p<.04

Major mood disorders: comorbidity with suicide attempts, anxiety/panic (%) Stars refer to significant p values between M/Md and BP-I p<.008

Clinical studies on unipolar mania (UM) BP-I N UM N UM % Western countries - 6 retrospective studies prospective studies Non-Western countries - 12 retrospective studies prospective study Angst, J. & Grobler, C., Eur Arch Psychiatry Clin Neurosci 2015 DOI /s

Diagnostic stability of unipolar mania (UM) DSM=Diagnostic and Statistical Manual of Mental Disorders RDC=Research Diagnostic Criteria BP-I= Bipolar-I Disorder CountryYearDiagnosis Min epis. Follow-up years Total sample UM% prospective Xu and ChenChina1992DSM-III mania retrospectiveAuthor MakanjuolaNigeria1982RDC mania2+1+ (median) Solomon et alUSA2003 BP-I or schizo- mania Yazici et al.Turkey2008DSM-IV mania Angst, J. & Grobler, C., Eur Arch Psychiatry Clin Neurosci 2015 DOI /s

Clinical characteristics of UM compared to BP-I (review of literature) Earlier onset Fewer episodes Lower comorbidity with anxiety disorders Better long-term adjustment More psychotic features Fewer suicide attempts Less rapid cycling Lower response to lithium Hyperthymic temperament Weaker family history for MDD Angst, J. & Grobler, C., Eur Arch Psychiatry Clin Neurosci 2015 DOI /s

Selection of consecutive admissions Prospective examinations M o r t a l i t y 1997 Outcome Affective disorder in-patient study: Zurich (N=403)

Mortality rates DiagnosisNDeathsDeaths % MDD=(D) BP-II=(Dm) BP-I=(MD) M/Md Total J. Angst et al. 2013: Eur Arch Psychiat Clin Neurosci 263:

Cardiovascular mortality (N=353 deaths) ** (*) J. Angst et al. 2013: Eur Arch Psychiat Clin Neurosci 263: *

Conclusions I Two large epidemiological studies identified M/Md in % of the population. In the Zurich Study most subjects with MDE were classified as having MDD and very few with BP-II, BP- I or M/Md. 45% of subjects with MDD reported manic symptoms and this group shows some signs of hidden bipolarity. Mania and BP-I were equally rare but differed in some respects: manic subjects tended to have a weaker family history of depression (50% vs 68%), were more often hyperthymic (44% vs 5%) but less often cyclothymic (22% vs 58%).

Conclusions II Associations with GAD and panic (58%) much stronger in BP-I disorder than in mania (17%), and a bit stronger with suicide attempts (BP-I:16%; mania:11%). Clinical studies suggest higher rates of psychotic symptoms, earlier age of onset, fewer episodes and better remission of mania compared to BP-I disorders. Deaths by suicide were highest in MDD and lowest in M/Md; the reverse was found for cardiovascular mortality. A diagnosis of M is best based on 3+ episodes. Much more research is needed on mania as an independent disorder. Our knowledge is still very limited.

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