Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Institute of Psychiatry, Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy; Department of Psychiatry, Yale University, School of Medicine, New Haven, CT, United States; Women's Brain Project (WBP), Switzerland.
Prog Neurobiol. 2022 Dec;219:102353. doi: 10.1016/j.pneurobio.2022.102353. Epub 2022 Sep 12.
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.
神经和神经精神疾病对男性和女性的影响不同。多发性硬化症、阿尔茨海默病、焦虑症、抑郁症、脑膜瘤和迟发性精神分裂症比男性更常见于女性。相比之下，帕金森病、自闭症谱系障碍、注意力缺陷多动障碍、妥瑞氏症、肌萎缩侧索硬化症和早发性精神分裂症在男性中更为普遍。在历史上，女性在临床试验中被招募或排除的情况较少，而且大多数基础研究使用雄性啮齿动物细胞或动物作为疾病模型，很少同时研究两性，并将性别作为潜在的变异来源，因此对疾病发展过程中性别和性别差异的潜在生物学原因了解不足。假定的病理生理学因素包括激素和表观遗传调节剂，但可能还有其他生物和非生物因素在起作用。在这里，我们回顾了性染色体组成、X 染色体失活以及环境和表观遗传调节剂在大脑疾病易感性性别差异中的潜在作用的证据。我们得出的结论是，迫切需要更好地了解维持这些疾病中性别差异的遗传、表观遗传和环境机制，这对于基于性别定制的预防和治疗的精准医学方法的发展至关重要。
