title: White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder.
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 Effectiveness 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 deviations 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 × 109/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). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient = 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 Depression Rating Scale scores increased significantly among men (coefficient = 1.09; 95% confidence interval = [0.31, -1.87]; p = 0.006) for each 1.0 × 109/L white blood cell deviation, whereas we found a weak association among women (coefficient = 0.55; 95% confidence interval = [-0.20, -1.29]; p = 0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender.
  
  
  CONCLUSIONS
  Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment.
authors.affiliation: 1 Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Köhler
authors.affiliation: 2 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|3 Harvard Medical School, Boston, MA, USA.
authors.forename: Louisa G
authors.initials: LG
authors.lastname: Sylvia
authors.affiliation: 4 Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.affiliation: 5 Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.affiliation: 6 Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Thase
authors.affiliation: 7 Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.affiliation: 8 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.affiliation: 9 Department of Psychiatry, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.affiliation: 10 Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Kocsis
authors.affiliation: 11 Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.affiliation: 12 Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Friedman
authors.affiliation: 2 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|3 Harvard Medical School, Boston, MA, USA.
authors.forename: Thilo
authors.initials: T
authors.lastname: Deckersbach
authors.affiliation: 11 Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA.|13 VA Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ostacher
authors.affiliation: 14 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.affiliation: 15 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.|16 Lindner Center of HOPE, Mason, OH, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: McElroy
authors.affiliation: 2 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|3 Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D001714:Bipolar Disorder / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007107:Immune System; D007958:Leukocyte Count; D016014:Linear Models; D008094:Lithium / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D012727:Sex Characteristics; D014481:United States; D055815:Young Adult
chemical_list: D008094:Lithium
keywords: Bipolar disorder; gender differences; immune system; symptom severity; white blood cells