Crespi Bernard, Badcock Christopher
Department of Biosciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Behav Brain Sci. 2008 Jun;31(3):241-61; discussion 261-320. doi: 10.1017/S0140525X08004214.
Autistic-spectrum conditions and psychotic-spectrum conditions (mainly schizophrenia, bipolar disorder, and major depression) represent two major suites of disorders of human cognition, affect, and behavior that involve altered development and function of the social brain. We describe evidence that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autistic-spectrum versus psychotic-spectrum conditions, with a focus on schizophrenia. This suite of traits is inter-correlated, in that autism involves a general pattern of constrained overgrowth, whereas schizophrenia involves undergrowth. These disorders also exhibit diametric patterns for traits related to social brain development, including aspects of gaze, agency, social cognition, local versus global processing, language, and behavior. Social cognition is thus underdeveloped in autistic-spectrum conditions and hyper-developed on the psychotic spectrum.;>We propose and evaluate a novel hypothesis that may help to explain these diametric phenotypes: that the development of these two sets of conditions is mediated in part by alterations of genomic imprinting. Evidence regarding the genetic, physiological, neurological, and psychological underpinnings of psychotic-spectrum conditions supports the hypothesis that the etiologies of these conditions involve biases towards increased relative effects from imprinted genes with maternal expression, which engender a general pattern of undergrowth. By contrast, autistic-spectrum conditions appear to involve increased relative bias towards effects of paternally expressed genes, which mediate overgrowth. This hypothesis provides a simple yet comprehensive theory, grounded in evolutionary biology and genetics, for understanding the causes and phenotypes of autistic-spectrum and psychotic-spectrum conditions.
自闭症谱系障碍和精神病性谱系障碍(主要是精神分裂症、双相情感障碍和重度抑郁症)代表了人类认知、情感和行为的两大主要疾病组,它们涉及社会脑的发育和功能改变。我们描述了一系列证据,表明大量表型特征在自闭症谱系障碍和精神病性谱系障碍中呈现出截然相反的表型,重点关注精神分裂症。这一系列特征相互关联,因为自闭症涉及一种普遍的过度生长受限模式,而精神分裂症则涉及生长不足。这些疾病在与社会脑发育相关的特征方面也呈现出截然相反的模式,包括注视、能动性、社会认知、局部与整体加工、语言和行为等方面。因此,社会认知在自闭症谱系障碍中发育不足,而在精神病性谱系中过度发育。
我们提出并评估了一个新的假说,该假说可能有助于解释这些截然相反的表型:这两组疾病的发展部分是由基因组印记的改变介导的。关于精神病性谱系障碍的遗传、生理、神经和心理基础的证据支持这样一种假说,即这些疾病的病因涉及偏向于母源表达的印记基因的相对效应增加,从而导致一种普遍的生长不足模式。相比之下,自闭症谱系障碍似乎涉及父源表达基因效应的相对偏向增加,这介导了过度生长。这个假说为理解自闭症谱系障碍和精神病性谱系障碍的病因和表型提供了一个基于进化生物学和遗传学的简单而全面的理论。