The clinical characterization of the adult patient with bipolar disorder aimed at personalization of management


Roger S. McIntyre, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Martin Alda, Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Ross J. Baldessarini, Harvard Medical School, Boston, MA, USA.
Michael Bauer, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Michael Berk, IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia.
Christoph U. Correll, Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
Andrea Fagiolini, Department of Molecular Medicine, University of Siena, Siena, Italy.
Kostas Fountoulakis, 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Mark A. Frye, Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA.
Heinz Grunze, Allgemeinpsychiatrie Ost, Klinikum am Weissenhof, Weinsberg, Germany.
Lars V. Kessing, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen, Denmark.
David J. Miklowitz, Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA) Semel Institute, Los Angeles, CA, USA.
Gordon Parker, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Robert M. Post, School of Medicine & Health Sciences, George Washington University, Washington, DC, USA.
Alan C. Swann, Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
Trisha Suppes, Department of Psychiatry and Behavioural Sciences, Stanford School of Medicine and VA Palo Alto Health Care -System, Palo Alto, CA, USA.
Eduard Vieta, Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Allan Young, Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Mario Maj, Department of Psychiatry, University of Campania "L. Vanvitelli", Naples, Italy.

Document Type

Journal Article

Publication Date



World psychiatry : official journal of the World Psychiatric Association (WPA)








Bipolar disorder; bipolar I disorder; bipolar II disorder; clinical characterization; cognition; comorbidity; depression; mania; mixed features; personalization; phenotyping; rapid cycling; resilience; social determinants; stigma; stressors; subtypes; trauma


Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal-ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical "multi-omic" measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point-of-care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features - especially during depressive episodes - and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally-oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point-of-care.


Psychiatry and Behavioral Sciences