RT Journal Article SR Electronic T1 Neuroimmune mechanisms and sex/gender-dependent effects in the pathophysiology of mental disorders JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.120.266163 DO 10.1124/jpet.120.266163 A1 Alexandros G Kokkosis A1 Stella E Tsirka YR 2020 UL http://jpet.aspetjournals.org/content/early/2020/07/14/jpet.120.266163.abstract AB Innate and adaptive immune mechanisms have emerged as critical regulators of CNS homeostasis and mental health. A plethora of immunological factors have been reported to interact with emotion- and behavior-related neuronal circuits, modulating susceptibility and resilience to mental disorders. However, it remains unclear whether immune dysregulation is a cardinal causal factor, or an outcome of the pathologies associated with mental disorders. Emerging variations in immune regulatory pathways based on sex differences provide an additional framework for discussion in these psychiatric disorders. In this review, we present the current literature pertaining to the effects that disrupted immune pathways have in mental disorder pathophysiology, including immune dysregulation in CNS and periphery, microglial activation, and disturbances of the blood-brain barrier. In addition, we present the suggested origins of such immune dysregulation, and discuss the gender and sex influence of the neuroimmune substrates which contribute to mental disorders. The findings challenge the conventional view of these disorders and open the window to a diverse spectrum of innovative therapeutic targets, which focus on the immune-specific pathophenotypes in neuronal circuits and behavior.SIGNIFICANCE STATEMENT The involvement of gender-dependent inflammatory mechanisms on the development of mental pathologies is gaining momentum. This review addresses these novel factors and presents the accumulating evidence introducing microglia and proinflammatory elements as critical components and potential targets, for the treatment of mental disorders.