Abstract
Sleep disturbance and depression are common, particularly in females, and sleep disturbance is a well-known risk factor for depression. Systemic inflammation has been suggested as a potential mechanism of this association. This study examined whether preexisting sleep disturbance acted as a vulnerability factor for depressed mood induced by an inflammatory challenge in healthy females vs males. In a randomized double-blind placebo-controlled design, volunteers aged 18–50 (N=111; 67 females) were assigned to placebo or low-dose endotoxin. Before substance administration, sleep disturbance was assessed using the Pittsburgh Sleep Quality Index and dichotomized using median split (⩾3 vs <3). Self-reported depressed mood (profile of mood states) and circulating proinflammatory cytokines (interleukin-6, tumor necrosis factor-α) were repeatedly assessed over 6 h. Among females, moderation of depressed mood by sleep disturbance was significant even after adjustment for covariates (X2=12.73, df=6, P<0.05). There was a robust time-by-condition interaction in females with sleep disturbance (X2=26.22, df=6, P<0.001), but not in females without sleep disturbance (X2=8.65, df=6, P=0.19). Although cytokines increased equally in all females, the correlations between cytokines and depressed mood were significantly stronger in females with sleep disturbance. Among males, no moderating effect of sleep disturbance was observed. Inflammation-induced depressed mood was considerably more severe among females reporting mild sleep disturbance compared with those reporting no sleep disturbance, suggesting that even mild sleep disturbance may increase vulnerability for inflammation-induced depression in females. Furthermore, sleep disturbance appears to increase the vulnerability to depression by augmenting affective sensitivity to cytokines rather than by enhancing cytokine responses to inflammatory challenge in females.
Highlights
Depression is a major public health burden because it is highly prevalent—the lifetime prevalence of major depression is almost 20% in the US general population1—and represents a leading cause of disability worldwide.[2]
Endotoxin administration turbance and depression, in females, we examined whether preexisting sleep disturbance enhanced the effect of an inflammatory challenge, endotoxin administration, on depressed mood among healthy females and males
Depressed mood changes in response to endotoxin and moderation by sleep disturbance As previously reported,[21] there was an important sex difference in changes of depressed mood following endotoxin; females experienced robust increases in depressed mood in response to endotoxin, whereas males exhibited no significant changes in Translational Psychiatry (2016), 1 – 7 depressed mood
Summary
Depression is a major public health burden because it is highly prevalent—the lifetime prevalence of major depression is almost 20% in the US general population1—and represents a leading cause of disability worldwide.[2] depression is projected to become the leading cause of disease burden by 2030.3 models for understanding and treating depression are critical. The dominant models of depression have focused on altered function in monoamine pathways, antidepressants—the mainstay of the current treatments for depression that target these pathways—typically only achieve remission rates of 30% or less when used as a monotherapy.[4] This suboptimal effectiveness has led researchers to study biologically plausible models that would translate into new treatment and prevention strategies. Systemic inflammation is hypothesized to have an important role on the onset and perpetuation of some forms of depression.[5]
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