Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions. (December 2022)

• Record Type: Journal Article
• Authors: Pallier, Patrick N.; Ferrara, Maria; Romagnolo, Francesca; Ferretti, Maria Teresa; Soreq, Hermona; Cerase, Andrea
• Is Part Of: Progress in neurobiology. Volume 219(2022)
• Publication Date: 2022-12
• Subjects: AD Alzheimer's disease -- ADHD Attention deficit hyperactivity disorder -- ALS amyotrophic lateral sclerosis -- ASC Autism spectrum condition -- BNST Bed nucleus of the stria terminalis -- CNS Central nervous system -- CRH Corticoliberin (Corticotropin-Releasing Factor) -- DHA Docosahexaenoic acid -- EAE Experimental autoimmune encephalomyelitis -- FCG Four core genotypes -- GABA Gamma-aminobutyric acid -- HPA Hypothalamic-pituitary-adrenal axis -- MIA Maternal immune activation -- MS Multiple sclerosis -- NPD Neuropsychiatric disorder -- PD Parkinson's disease -- PUFA Polyunsaturated fatty acid -- PVN Paraventricular nucleus of the hypothalamus -- Sry/SRY Sex-determining region Y -- TH Tyrosine hydroxylase -- XCI X chromosome inactivation -- Xi Inactive X chromosome -- Xist X-inactive specific transcript; X chromosome inactivation (XCI) -- Inactive X chromosome (Xi) -- Epigenetics -- Sex chromosome complement -- Stress -- Neuroinflammation -- Hormones -- Diet -- Nutrition -- Neuropsychiatric diseases -- Precision medicine -- Gender medicine -- Non-coding RNA regulators -- Schizophrenia -- Mental disorders; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2022.102353
• Languages: English
• ISSNs: 0301-0082

Abstract

Abstract: Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer's disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson's disease, autism spectrum condition, attention-deficit hyperactivity disorder, Tourette's syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment.