Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, CA, 94305, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94305, USA.
Neuropsychopharmacology. 2019 Jan;44(1):9-21. doi: 10.1038/s41386-018-0153-2. Epub 2018 Jul 16.
The study of sexual dimorphism in psychiatric and neurodevelopmental disorders is challenging due to the complex interplay of diverse biological, psychological, and social factors. Males are more susceptible to neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and attention-deficit activity disorder. Conversely, after puberty, females are more prone to major depressive disorder and anxiety disorders compared to males. One major biological factor contributing to sex differences is the sex chromosomes. First, the X and Y chromosomes have unique and specific genetic effects as well as downstream gonadal effects. Second, males have one X chromosome and one Y chromosome, while females have two X chromosomes. Thus, sex chromosome constitution also differs between the sexes. Due to this complexity, determining genetic and downstream biological influences on sexual dimorphism in humans is challenging. Sex chromosome aneuploidies, such as Turner syndrome (X0) and Klinefelter syndrome (XXY), are common genetic conditions in humans. The study of individuals with sex chromosome aneuploidies provides a promising framework for studying sexual dimorphism in neurodevelopmental and psychiatric disorders. Here we will review and contrast four syndromes caused by variation in the number of sex chromosomes: Turner syndrome, Klinefelter syndrome, XYY syndrome, and XXX syndrome. Overall we describe an increased rate of attention-deficit hyperactivity disorder and autism spectrum disorder, along with the increased rates of major depressive disorder and anxiety disorders in one or more of these conditions. In addition to contributing unique insights about sexual dimorphism in neuropsychiatric disorders, awareness of the increased risk of neurodevelopmental and psychiatric disorders in sex chromosome aneuploidies can inform appropriate management of these common genetic disorders.
性二态性在精神和神经发育障碍中的研究具有挑战性，因为其涉及到多种生物学、心理学和社会因素的复杂相互作用。男性更容易患神经发育障碍，包括智力障碍、自闭症谱系障碍和注意力缺陷多动障碍。相反，青春期后，女性比男性更容易患重度抑郁症和焦虑症。导致性别差异的一个主要生物学因素是性染色体。首先，X 和 Y 染色体具有独特而特定的遗传效应以及下游性腺效应。其次，男性有一条 X 染色体和一条 Y 染色体，而女性有两条 X 染色体。因此，性染色体组成在两性之间也存在差异。由于这种复杂性，确定遗传和下游生物学因素对人类性二态性的影响具有挑战性。性染色体非整倍体，如特纳综合征（X0）和克氏综合征（XXY），是人类常见的遗传疾病。研究性染色体非整倍体个体为研究神经发育和精神障碍中的性二态性提供了一个有前景的框架。在这里，我们将回顾和对比由性染色体数量变异引起的四种综合征：特纳综合征、克氏综合征、XYY 综合征和 XXX 综合征。总体而言，我们描述了这些情况下注意力缺陷多动障碍和自闭症谱系障碍的发生率增加，以及重度抑郁症和焦虑症的发生率增加。除了为神经精神障碍中的性二态性提供独特的见解外，对性染色体非整倍体中神经发育和精神障碍风险增加的认识可以为这些常见遗传疾病的适当管理提供信息。
