Australian & New Zealand Journal of Psychiatry, 51(4) Editor’s Choice https://doi.org/10.1177/0004867416644508 Australian & New Zealand Journal of Psychiatry 2017, Vol. 51(4) 355–365 DOI: 10.1177/0004867416644508 © The Royal Australian and New Zealand College of Psychiatrists 2016 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav journals.sagepub.com/home/anp White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder Ole Köhler 1 , Louisa G Sylvia 2,3 , Charles L Bowden 4 , Joseph R Calabrese 5 , Michael Thase 6 , Richard C Shelton 7 , Melvin McInnis 8 , Mauricio Tohen 9 , James H Kocsis 10 , Terence A Ketter 11 , Edward S Friedman 12 , Thilo Deckersbach 2,3 , Michael J Ostacher 11,13 , Dan V Iosifescu 14 , Susan McElroy 15,16 and Andrew A Nierenberg 2,3 Abstract Objective: Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown. Methods: The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effec- tiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between devia- tions from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia. Results: Among 482 Bipolar CHOICE participants, for each 1.0 × 10 9 /L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient = 2.13; 95% confidence interval = [0.46, -3.79]; p = 0.013), but not among women (coefficient = 0.87; 95% confidence interval = [-0.87, -2.61]; p = 0.33). Interac- tion analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coef- ficient = 1.51; 95% confidence interval = [-0.81, -3.82]; p = 0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient = 1.33; 95% confidence interval = [-0.22, -2.89]; p = 0.09), but not among women (coefficient = 0.34; 95% confidence interval = [-0.64, -1.32]; p = 0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg 1 Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark 2 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA 3 Harvard Medical School, Boston, MA, USA 4 Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 5 Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA 6 Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA 7 Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA 8 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA 9 Department of Psychiatry, University of New Mexico Health Science Center, Albuquerque, NM, USA 10 Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA 11 Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA 12 Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA 13 VA Palo Alto Health Care System, Palo Alto, CA, USA 14 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA 15 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH, USA 16 Lindner Center of HOPE, Mason, OH, USA Corresponding author: Ole Köhler, Psychosis Research Unit, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. Email: karkoe@rm.dk 644508ANP 0 0 10.1177/0004867416644508ANZJP ArticleKöhler et al. research-article 2016 Research