Disturbance in the duration, quality, and timing of sleep has been associated with an assortment of adverse health outcomes.1 During the past decade, surreal insights regarding chronobiology and sleep behavior have been made. In addition to being a common human disturbance affecting a significant percentage of the general population, disturbance in sleep is a common symptom of many and disparate medical and psychiatric disorders and is highly associated with cognitive impairment.2,3 Moreover, disturbance in sleep may also predate the full declaration of a common and/or severe mental disorder.4-6 For example, longitudinal studies indicate that individuals with sleep disturbances are more likely to develop major depressive disorder and bipolar disorder.
The foregoing observation introduces a testable hypothesis that perhaps sleep disturbances may have heterotypic continuity with mood (and other mental) disorders. The possibility that sleep disturbance, and more specifically chronobiological perturbations, may be an endophenotype of mental disorder is suggested by observations that unaffected first-degree relatives of probands with mood disorders are significantly more likely to evince disturbance in circadian rhythm physiology.7 Experienced clinicians are not only fully aware of how common sleep complaints are but also how frequently they continue as residual symptomatology and presage relapse of mental disorders (eg, bipolar disorder). In addition to the well-established association between sleep disturbance and mental disorders, a robust association exists linking chronobiological disturbances to common medical disorders such as hypertension, obesity, type 2 diabetes, and cardiovascular disease.8-10 The convergent finding that individuals with mood disorders are differentially affected by the foregoing common chronic medical disorders suggests that sleep disturbance maybe an epiphenomenon of a disturbed neurobiologic process subserving both mood disorders and cardiometabolic disturbances.
Preclinical and clinical data indicate that disturbance in the inflammatory homeostatic system is etiopathogenically related to the onset, progression, comorbidity, and possibly treatment of mental disorders (eg, mood disorders).11 It is also well established that disturbances in inflammatory effector systems are a critical pathophysiologic process of a cardiometabolic syndrome.8 The convergent mechanistic role of inflammation in both mental and medical disorders herein invites the need to identify specific molecular and behavioral processes that yoke mood and medical disorders.12
Alterations in sleep may represent both cause and consequence of mental and medical disorders. More specifically, the chronobiological disturbances may be the convergent pathophysiologic nexus spanning both conditions. It has been recently established that disturbances in sleep (ie, sleep disruption or sleep of extremely short or long duration) are associated with increased levels of C-reactive peptide and proinflammatory cytokines (eg, interleukin-6).13,14