Aging: Sleep and Inflammatory Mechanism in Depression Prevention

Depression, one of the most common diseases in older adults, carries significant risk for morbidity, and mortality. However, many older adults with depression are not identified and even when identified, they face protracted courses of treatment, with over 60% of elderly patients failing to achieve symptomatic remission. Given the burgeoning population of older adults, as well as the enormous burden of depression, efforts to maximize depression prevention are needed.

Despite advances in understanding the behavioral pathways that contribute to depression, there has been little attention aimed at targeting behavioral risk factors such as sleep disturbance, even though such strategies have the potential to optimize efficiency (i.e., decrease number needed to treat (NNT) among vulnerable older adults with a history of depression. In this study, we hypothesize that recognition and treatment of sleep disturbance, a modifiable behavioral risk factor, will prevent depression incidence in older adults. Whereas sleep disturbance in depressed patients often lingers and its persistence can represent a residual phase of a major mood disorder, emergence of disturbed sleep in non-depressed older adults serves as an independent risk factor depression that occurs later in life. In a 2-year prospective cohort study of community-dwelling older adults aged 60 years or older (N=351), we have found that sleep disturbance is prospectively associated with depression incidence independent of other current depressive symptoms, as well as antidepressant and hypnotic medication use, and medical status. To evaluate sleep disturbance at the community level, sleep disturbance was defined by a self-report measure (i.e. scores > 5 on the Pittsburgh Sleep Quality Index (PSQI), which highly correlates with insomnia diagnosis. We have found similar prospective results between reported sleep disturbance and depression in adults (N=1716).

Increasing evidence also implicates inflammation as a biological mechanism that contributes to depression, and we further hypothesize that increases in inflammation are associated with the link between sleep disturbance and depression incidence. Whereas multiple other factors including but not limited to, psychosocial stress, medical illness, obesity, sedentary lifestyle, social isolation, low socio-economic status, female sex, and smoking can drive inflammation and are associated with depression, our preliminary data have found that sleep disturbance induces activation of inflammatory signaling,and additional naturalistic and epidemiologic preliminary findings show that sleep disturbance is associated with increases in markers of inflammation especially among those with a history of depression. In turn, we and others have found that inflammation prospectively predicts depression recurrence in community dwelling adults who have a history of depression (N=1716)16 Although there is also evidence that this association can be reciprocal,33 our experimental preliminary data show that inflammatory activation induces depressed mood. In contrast, cognitive behavioral therapy for insomnia (CBT-I)) reduces cellular markers of inflammation in older adults who show a remission of clinical sleep complaints.

The over-arching objectives of this study are to evaluate the ability of CBT-I vs. an active comparator control, Sleep Education Therapy (SET) to reduce sleep complaints, depression incidence, and cellular and genomic markers of inflammation in older adults with self-reported sleep disturbance with follow-up up to three years.