Insomnia and Inflammation Conspire to Heighten Depression Risk: Implications for Treatment and Prevention of Mood Disorders

Insomnia is ubiquitous, is comorbid with all major mental disorders, increases the risk of depression, and contributes to inflammatory morbidity and all-cause mortality. This review examines the relationships between insomnia and inflammation in the pathophysiology of depression. The unique role of insomnia on depression risk is examined with interrogation of what aspects of sleep disturbance contribute to depressed mood. Furthermore, the influence of insomnia and its specific aspects (i.e., short sleep duration, disturbance of sleep maintenance) on affective mechanisms are considered, with a focus on reward activation and emotion processing. Given that inflammation contributes to some types of depression, the bidirectional interactions between sleep and inflammation are examined with consideration of how sleep deprivation induces activation of systemic, cellular, and genomic inflammatory outcomes and the causal role of inflammation in precipitating depressed mood and depressive symptoms. Key gaps in the literature linking insomnia and inflammation to depression risk are identified, and maps for future research are proposed. In particular, this review considers how the components of insomnia and inflammation conspire together to exaggerate deficits in reward activation and recognition of emotion, which underlie depression risk and adverse depression outcomes. Finally, informed by this two-hit model of insomnia and inflammation on depression risk, this review examines the efficacy of behavioral interventions that target insomnia and reverse related inflammation and discusses their potential to refine therapeutic approaches for depression treatment and prevention in individuals with insomnia.