Self-Reported Sleep Quality Modulates Amygdala Resting-State Functional Connectivity in Anxiety and Depression

Sufficient sleep plays an important role in neurocognitive function, yet, problematic sleep is ubiquitous in the general population. It is also frequently predictive of, and concurrent with, internalizing psychopathologies (IPs) such as anxiety and depression suggesting sleep quality is dimensional and transdiagnostic. Along with problematic sleep, IPs are characterized by negative affectivity, therefore, prominent neurobiological models of internalizing conditions involve the amygdala, a region central to emotion. In resting-state studies (independent of sleep considerations), abnormalities in amygdala-frontal functional connectivity are commonly observed suggesting emotion dysregulation may contribute to clinically-relevant phenotypes. In a separate line of research, studies of sleep deprivation and insomnia disorder suggest sleep loss may alter amygdala-frontal connectivity. Taken together, findings point to shared neurobiology between sleep and emotion systems, however, the impact of sleep quality on the amygdala circuit in anxiety or depression is unclear. Therefore, we evaluated variance in naturalistic sleep quality on amygdala-based circuity in individuals with and without psychiatric illness. Resting-state fMRI data was collected in 87 un-medicated, treatment-seeking adults diagnosed with a primary anxiety disorder (n=68) or primary depressive disorder (n=19) in addition to healthy individuals (n=40). Regression analysis was conducted with bilateral anatomical amygdala as seed regions and self-reported sleep quality was indexed with a validated self-report measure, the Pittsburgh Sleep Quality Index (PSQI). Post-hoc analysis was performed to evaluate whether diagnostic status (primary anxiety, primary depression, healthy) significantly explained functional connectivity results. Whole-brain regression analysis, controlling for anxiety and depression symptoms, revealed worse sleep quality (i.e., higher PSQI total scores) predicted increased left amygdala-subgenual anterior cingulate functional connectivity and reduced connectivity with posterior cerebellar lobe and superior temporal gyrus. For right amygdala, increased coupling with postcentral gyrus corresponded with worse sleep. Post-hoc analysis did not detect a significant relationship between diagnostic status and whole-brain findings. Results expand on previous studies and indicate variance in sleep quality tracks brain pathways involved in cognitive-emotion functions implicated in the neurobiology of IPs that may extend to individuals at risk for clinical anxiety or depression. Altogether, the clinical relevance of identifying phenotypes to improve our understanding of psychopathology may be improved by incorporating sleep quality.