Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?
Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?
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DOI：
10.1038/npp.2016.79
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发表时间：
2017-01-01
影响因子：
7.6
通讯作者：
McCarthy, Margaret M.
中科院分区：
文献类型：
--
作者：
Joel, Daphna;McCarthy, Margaret M.
了解性可以改变大脑的多种方式对于制定有益于所有人类的政策和治疗方法至关重要。这在神经精神药理学领域尤其如此，因为许多神经精神疾病在频率、严重程度或对治疗的反应方面表现出性别偏见。本文的目的是提供两种观点，一种是关于性与大脑之间关系的最新研究现状，一种是关于性与大脑之间关系的研究，这种关系几乎完全是通过在特定的终点上比较女性和男性来研究的，从基因表达到行为。我们首先提出一个框架，定义什么是被测量的，它意味着什么。我们认为，“性别差异”可以分为四个维度：（1）持久与短暂的整个生命周期;（2）上下文独立与依赖;（3）二态性与连续;（4）直接与间接的后果的性别。为了准确地将性别差异沿着这些维度进行分类，可能需要在不同条件下比较女性和男性。接下来，我们将讨论目前关于大脑性别分化机制和大脑性别差异的数据，从而得出结论，每个男性和女性的大脑都是相对男性化、女性化和相同性的马赛克，理论上可以产生无限多样的个体。我们还提出了大脑中性别差异的可能性，这可能会增强和抑制男性和女性之间的差异。最后，我们讨论在研究神经精神疾病时如何考虑性。
Understanding the multiplicity of ways in which sex can alter the brain is essential to crafting policies and treatments that are beneficial for all human beings. This is particularly true for the field of neuropsychopharmacology, as many neuropsychiatric disorders exhibit gender bias in the frequency, severity, or response to treatment. The goal of this circumspective is to provide two views on the current state of the art of the relations between sex and the brain, relations that are studied almost exclusively by comparing females and males on specific end points, from gene expression to behavior. We start by suggesting a framework for defining what is being measured and what it means. We suggest that 'sex differences' can be classified on four dimensions: (I) persistent vs transient across the lifespan; (2) context independent vs dependent; (3) dimorphic vs continuous; and (4) a direct vs an indirect consequence of sex. To accurately classify a sex difference along these dimensions, one may need to compare females and males under varied conditions. We next discuss current data on the mechanisms of sexual differentiation of the brain and on sex differences in the brain to conclude that the brain of each male and female is a mosaic of relative masculinization, feminization, and sameness, which theoretically could produce an infinite variety of individuals. We also raise the possibility that sex differences in the brain are canalized, which may act to both enhance and restrain variation between males and females. We end by discussing ways to consider sex when studying neuropsychiatric disorders.