The Compensatory Immune-Regulatory Reflex System (CIRS) in Depression and Bipolar Disorder

AbstractHere, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors. These immune aberrations appear to be evident during the course of major affective episodes of either depressive or (hypo) manic polarity. Here, we review (a) the current state of the art of CIRS functions in both mood disorders and (b) the possible role of CIRS-related biomarkers for the understanding of affective disorders within the framework of precision psychiatry that could also provide novel drug targets for both MDD and BD. CIRS-related abnormalities in mood disorders include elevated Th-2 and T regulatory (Treg) activities with increased IL-4 and IL-10 production, classical IL-6 signaling, increased levels of sIL-1R antagonist (sIL-1RA), soluble IL-2 (sIL-2R) and tumor necrosis factor –α- receptors, and positive APPs, including haptoglobin, hemopexin, α1-acid glycoprotein, α1-antitrypsin, and ceruloplasmin. It is concluded that CIRS is involved in MDD and BD by regulating the primary immune-inflammatory response, thereby c...
Source: Molecular Neurobiology - Category: Neurology Source Type: research