A Pattern to Link Adenosine Signaling, Circadian System, and Potential Final Common Pathway in the Pathogenesis of Major Depressive Disorder

Several studies have reported separate roles of adenosine receptors and circadian clockwork in major depressive disorder. While less evidence exists for regulation of the circadian clock by adenosine signaling, a small number of studies have linked the adenosinergic system, the molecular circadian clock, and mood regulation. In this article, we review relevant advances and propose that adenosine receptor signaling, including canonical and other alternative downstream cellular pathways, regulates circadian gene expression, which in turn may underlie the pathogenesis of mood disorders. Moreover, we summarize the convergent point of these signaling pathways and put forward a pattern by which Homer1a expression, regulated by both cAMP-response element binding protein (CREB) and circadian clock genes, may be the final common pathogenetic mechanism in depression.