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Inflammatory Markers Among Adolescents and Young Adults With Bipolar Spectrum Disorders

Benjamin I. Goldstein, MD, PhDa,*; Francis Lotrich, MD, PhDb; David A. Axelson, MDc; Mary Kay Gill, RN, MSNb; Heather Hower, MSWd; Tina R. Goldstein, PhDb; Jieyu Fan, PhDb; Shirley Yen, PhDd; Rasim Diler, MDb; Daniel Dickstein, MDd; Michael A. Strober, PhDe; Satish Iyengar, PhDf; Neal D. Ryan, MDb; Martin B. Keller, MDd; and Boris Birmaher, MDb

Published: November 25, 2015

Article Abstract

Objective: Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study.

Method: Subjects were 123 adolescents and young adults (mean [SD] = 20.4 ± 3.8 years; range, 13.4-28.3 years) in COBY, enrolled between October 2000 and July 2006. DSM-IV diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Clinical characteristics during the preceding 6 months, including mood, comorbidity, and treatment, were evaluated using the Longitudinal Interval Follow-Up Evaluation (LIFE). Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were assayed. Primary analyses examined the association of PIMs with bipolar disorder characteristics during the preceding 6 months.

Results: Several lifetime clinical characteristics were significantly associated with PIMs in multivariable analyses, including longer illness duration (P = .005 for IL-6; P = .0004 for hsCRP), suicide attempts (P = .01 for TNF-α), family history of suicide attempts or completion (P = .01 for hsCRP), self-injurious behavior (P = .005 for TNF-α), substance use disorder (SUD) (P < .0001 for hsCRP), and family history of SUD (P = .02 for TNF-α; P = .01 for IL-6). The following bipolar disorder characteristics during the preceding 6 months remained significantly associated with PIMs in multivariable analyses that controlled for differences in comorbidity and treatment: for TNF-α, percentage of weeks with psychosis (χ2 = 5.7, P = .02); for IL-6, percentage of weeks with subthreshold mood symptoms (χ2 = 8.3, P = .004) and any suicide attempt (χ2 = 6.1, P = .01); for hsCRP, maximum severity of depressive symptoms (χ2 = 8.3, P = .004).

Conclusions: Proinflammatory markers may be relevant to bipolar disorder characteristics as well as other clinical characteristics among adolescents and young adults with bipolar disorder. Traction toward validating PIMs as clinically relevant biomarkers in bipolar disorder will require repeated measures of PIMs and incorporation of relevant covariates.

Volume: 76

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