Integrative transcriptomics reveals sexually dimorphic control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Mental diseases show sex-specific differences over a wide range of ages (e.g., in autism spectrum disorder (ASD), bipolar disorder (BP) or schizophrenia (SCZ)), and/or environmental susceptibilities (e.g., to prenatal viral exposure, stress or acute and chronic psychological stressors). However, the molecular mechanisms explaining sex differences in the onset and progression of these diseases and their diagnostic, preventive, and therapeutic implications remain elusive. Exploring the corresponding mechanisms is hence a pertinent and understudied topic of utmost importance and urgency. Here, I cover some causes of these sex-related differences and discuss putative pathway contributors to them by combining data from molecular psychiatry, neurogenetics, neuroinflammation, neuroendocrinology, and neuropsychopharmacology. For this purpose, thus, I discuss large-scale RNA-sequencing analyses, advanced immunology and cell biology research tools, and the use of human-derived tissues and new datasets. Seeking new concepts and innovative solutions to the sex-related differences in mental health can be interesting to many, and identifying the molecular players responsible for sex-specific differences in mental impairments can initiate future sex-targeted diagnosis, delay of disease onset, and development of gender-specific therapeutic interventions.