The Immunologic Underpinnings of Post-Stroke Depression

Post-stroke depression is a common consequence of stroke with an estimated prevalence of approximately 30% in stroke patients. It negatively impacts both rehabilitation and quality of life after stroke. Stroke induces an acute activation of the immune system in the central nervous system with concomitant immunologic alterations in the periphery. Immunologic alterations have been associated with non-stroke-related depression, and the evidence points to both central and peripheral immune activation with bidirectional interactions. By identifying and evaluating the current evidence of immunologic alterations associated with depression, stroke, and post-stroke depression, we outline the current knowledge and hypotheses on stroke-related immunologic alterations and associations with the subsequent risk of post-stroke depression. This includes immune system alterations in the cerebrospinal fluid and blood; pre- and post-stroke infections; the blood-brain barrier; autoimmunity of the central nervous system; brain imaging; the spleen-brain, gut-brain, and neuroendocrine-immune axes; and immunogenetic studies. All these topics are discussed within the context of post-stroke depression, pointing to a potential involvement of a multifactorial immunologic pathophysiology. In this narrative review, we identify key directions for future research and conclude by offering perspectives related to the therapeutic potential and associated challenges of this underinvestigated but important topic in neuropsychiatry.