Title:Circadian Rhythms and Sleep Disorders Associated to Major Depressive
Disorder: Pathophysiology and Therapeutic Opportunities
Volume: 23
Issue: 9
Author(s): Luana M. Manosso, Luciano A. Duarte, Nicoly S. Martinello, Gisiane B. Mathia and Gislaine Z. Réus*
Affiliation:
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina
(UNESC), Criciúma, SC, Brazil
Keywords:
Hypothalamic-pituitary-adrenal, neuroinflammation, microbiota-gut-brain axis, circadian rhythms, sleep disorders, major depressive disorder.
Abstract: Major depressive disorder (MDD) is a complex mood disorder. While much progress has
been made in understanding the pathophysiology of MDD, no single mechanism can explain all
facets of this disorder. Several studies show that disturbances in biological rhythms can lead to the
development of MDD. Indeed, insomnia or hypersomnia are symptoms included in the MDD diagnostic
criteria. Clinical studies and meta-analyses showed a strong relationship between MDD and
sleep disorders. Sleep disorder and MDD are associated with activation in the hypothalamicpituitary-
adrenal (HPA) axis and inflammation. The increase in inflammatory response can activate
the kynurenine pathway, decrease serotonin synthesis, and affect other factors involved in the pathophysiology
of neuropsychiatric conditions. Moreover, sleep disorders and MDD can change the gut
microbiota and alter the microbiota-gut-brain axis. Thus, this review discusses the relationship
between MDD, circadian rhythms, and sleep disorders, describing the potential pathophysiological
mechanism shared in these conditions. In addition, therapeutic opportunities based on antiinflammatory,
antioxidant, HPA axis regulatory, and synapse-modulating actions are raised. For the
article search, we used the PubMed database. Both sleep disorders and changes in biological
rhythms have a bidirectional relationship with MDD. Although some pathophysiological mechanisms,
including inflammation, changes in the gut microbiota, and decreased neuroplasticity, may
be involved in the relationship between sleep, circadian rhythms, and MDD, other mechanisms are
not yet well understood. Therapeutic opportunities based on anti-inflammatory, antioxidant, HPA
regulatory axis, and synapse modulating actions appear to be promising targets in preventing MDD,
circadian rhythm disturbances, and sleep disorders.