Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-[MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (= .05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (< .01), but it was counter-balanced by a compensatory increase in anti-inflammatory cytokines (= .02), reducing their total inflammatory burden from higher BMI. In patients, linear regression showed that two inflammatory cytokines predicted depressive relapse in the 12 months after cytokine measurement: IL-1α (< .01) and MCP-(< .01). These results suggest that elevated BMI is a significant contributor to inflammation in BD, more so even than recent mood illness severity. They also point to inflammation as an important predictor of illness course, particularly depressive relapse.
Bibliographical noteFunding Information:
Dr. Yatham is on speaker/advisory boards for, or has received research grants from: AstraZeneca, Bristol–Myers Squibb, CIHR, CANMAT, Eli Lilly, GlaxoSmithKline, Janssen, the Michael Smith Foundation for Health Research, Pfizer, Servier and the Stanley Foundation.
Dr. Lam is on speaker/advisory boards for, or has received research grants from: AstraZeneca, Bristol–Myers Squibb, Canadian Institutes of Health Research, Canadian Psychiatric Association, Canadian Psychiatric Association Foundation, CANMAT, Eli Lilly, Litebook Company Ltd., Lundbeck, Lundbeck Institute, Merck, Mochida, Pfizer, Servier, St., Jude Medical, UBC Institute of Mental Health/Coast Capital Savings, Takeda and Wyeth.
Dr. Bond has received speaking fees or sat on advisory boards for: the Canadian Network for Mood and Anxiety Treatments (CANMAT), the Canadian Psychiatric Association, Pfizer, Sunovion, BMS, Otsuka, Astra-Zeneca, Janssen-Ortho, and Myriad; and has received research support from: the Canadian Institutes of Health Research (CIHR), the UBC Institute of Mental Health/Coast Capital Depression Research Fund, and Pfizer.
Dr. Andreazza has received grants from Brain and Behaviour Foundation (formerly NARSAD) and CIHR.
The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada . The analysis of serum cytokines was supported by an investigator-initiated grant ( WS1952848 ) to DJB from Pfizer Canada . The sponsors had no input into the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
© 2015 Elsevier Ltd.
- Bipolar disorder
- Body mass index