Proinflammatory Cytokines, Mood, and Sleep in Interepisode Bipolar Disorder and Insomnia: A Pilot Study With Implications for Psychosocial Interventions

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Proinflammatory cytokines are associated with bipolar disorder (BD), but less is known about how cytokines function during the interepisode period. This study examined cytokines, mood symptoms, and sleep in individuals with interepisode BD with complaints of insomnia. We also investigated the effects of a BD-specific modification of cognitive behavior therapy for insomnia (CBTI-BP) on cytokine levels.


Twenty-two adults with interepisode BD type I and insomnia were drawn from a subset of a National Institute of Mental Health funded study. Participants were randomly allocated to CBTI-BP (n = 11) or psychoeducation (n = 11). Participants completed a sleep diary, rated self-report measures of mania and depression, and provided samples assayed for interleukin (IL)-6 and tumor necrosis factor soluble receptor 2 (sTNF-R2).


IL-6 was associated with mania symptoms (rs = 0.44, p = .041) and total sleep time (rs = −0.49, p = .026). IL-6 was related to depression symptoms at the trend level (rs = 0.43, p = .052). sTNF-R2 was not significantly related to mood or sleep measures. From pretreatment to posttreatment, CBTI-BP compared with psychoeducation was associated with a nonsignificant, large effect size decrease in IL-6 (z = −1.61, p = .13, d = −0.78) and a nonsignificant, small-medium effect size decrease in sTNF-R2 (z = −0.79, p = .44, d = −0.38).


These findings provide preliminary evidence that IL-6 is related to mania symptoms and shorter total sleep time in interepisode BD. A treatment that targets sleep in BD could potentially decrease IL-6 although replication is warranted.

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