Department of Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Pappajohn Biomedical Discovery Building, 169 Newton Road, Iowa City, IA, 52242, USA.
Center for Neurobiology and Behavior, Department of Psychiatry, Translational Research Laboratory, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, Room 2202, Philadelphia, PA, 19104-3403, USA.
Curr Psychiatry Rep. 2018 Mar 5;20(2):9. doi: 10.1007/s11920-018-0874-2.
Neurodevelopmental disorders disproportionately affect males. The mechanisms underlying male vulnerability or female protection are not known and remain understudied. Determining the processes involved is crucial to understanding the etiology and advancing treatment of neurodevelopmental disorders. Here, we review current findings and theories that contribute to male preponderance of neurodevelopmental disorders, with a focus on autism.
Recent work on the biological basis of the male preponderance of autism and other neurodevelopmental disorders includes discussion of a higher genetic burden in females and sex-specific gene mutations or epigenetic changes that differentially confer risk to males or protection to females. Other mechanisms discussed are sex chromosome and sex hormone involvement. Specifically, fetal testosterone is involved in many aspects of development and may interact with neurotransmitter, neuropeptide, or immune pathways to contribute to male vulnerability. Finally, the possibilities of female underdiagnosis and a multi-hit hypothesis are discussed. This review highlights current theories of male bias in developmental disorders. Topics include environmental, genetic, and epigenetic mechanisms; theories of sex chromosomes, hormones, neuroendocrine, and immune function; underdiagnosis of females; and a multi-hit hypothesis.
神经发育障碍在男性中发病率不成比例。男性易感性或女性保护的机制尚不清楚，也未得到充分研究。确定所涉及的过程对于理解神经发育障碍的病因和推进治疗至关重要。在这里，我们综述了导致神经发育障碍男性发病率较高的现有发现和理论，重点是自闭症。
最近关于自闭症和其他神经发育障碍男性发病率较高的生物学基础的研究工作包括讨论女性遗传负担较高，以及性别特异性基因突变或表观遗传变化，这些变化会使男性面临风险，而使女性得到保护。讨论的其他机制包括性染色体和性激素的参与。具体而言，胎儿睾酮参与了发育的许多方面，可能与神经递质、神经肽或免疫途径相互作用，导致男性易感性。最后，还讨论了女性漏诊的可能性和多打击假说。本综述重点介绍了目前关于发育障碍中男性偏倚的理论。讨论的主题包括环境、遗传和表观遗传机制；性染色体、激素、神经内分泌和免疫功能的理论；女性漏诊；以及多打击假说。
