The prevalence of autism spectrum disorder (ASD)—a type of neurodevelopmental disorder—is increasing and is around 2% in North America, Asia, and Europe. Besides the known genetic link, environmental, epigenetic, and metabolic factors have been implicated in ASD etiology. Although highly heterogeneous at the behavioral level, ASD comprises a set of core symptoms including impaired communication and social interaction skills as well as stereotyped and repetitive behaviors. This has led to the suggestion that a large part of the ASD phenotype is caused by changes in a few and common set of signaling pathways, the identification of which is a fundamental aim of autism research. Using advanced bioinformatics tools and the abundantly available genetic data, it is possible to classify the large number of ASD-associated genes according to cellular function and pathways. Cellular processes known to be impaired in ASD include gene regulation, synaptic transmission affecting the excitation/inhibition balance, neuronal Ca²⁺ signaling, development of short-/long-range connectivity (circuits and networks), and mitochondrial function. Such alterations often occur during early postnatal neurodevelopment. Among the neurons most affected in ASD as well as in schizophrenia are those expressing the Ca²⁺-binding protein parvalbumin (PV). These mainly inhibitory interneurons present in many different brain regions in humans and rodents are characterized by rapid, non-adaptive firing and have a high energy requirement. PV expression is often reduced at both messenger RNA (mRNA) and protein levels in human ASD brain samples and mouse ASD (and schizophrenia) models. Although the human PVALB gene is not a high-ranking susceptibility/risk gene for either disorder and is currently only listed in the SFARI Gene Archive, we propose and present supporting evidence for the Parvalbumin Hypothesis, which posits that decreased PV level is causally related to the etiology of ASD (and possibly schizophrenia).

自闭症谱系障碍 (ASD)（一种神经发育障碍）的患病率正在增加，在北美、亚洲和欧洲约为 2%。除了已知的遗传联系外，环境、表观遗传和代谢因素也与 ASD 病因有关。尽管自闭症谱系障碍在行为层面上存在高度异质性，但它包含一系列核心症状，包括沟通和社交技能受损以及刻板和重复的行为。这导致有人提出，很大一部分自闭症谱系障碍表型是由少数常见信号通路的变化引起的，识别这些信号通路是自闭症研究的基本目标。利用先进的生物信息学工具和丰富的遗传数据，可以根据细胞功能和途径对大量 ASD 相关基因进行分类。已知 ASD 中受损的细胞过程包括基因调控、影响兴奋/抑制平衡的突触传递、神经元 Ca ²⁺信号传导、短程/长程连接（电路和网络）的发展以及线粒体功能。这种改变经常发生在产后早期神经发育过程中。在 ASD 和精神分裂症中受影响最严重的神经元是那些表达 Ca ²⁺结合蛋白小清蛋白 (PV) 的神经元。这些主要是抑制性中间神经元存在于人类和啮齿动物的许多不同大脑区域中，其特征是快速、非适应性放电，并且具有高能量需求。在人类 ASD 大脑样本和小鼠 ASD（和精神分裂症）模型中，PV 表达在信使 RNA (mRNA) 和蛋白质水平上通常都会降低。 虽然人类聚乙烯吡咯烷酮基因不是这两种疾病的高级易感性/风险基因，目前仅列在 SFARI 基因档案中，我们提出并提供小白蛋白假说的支持证据，该假说认为 PV 水平下降与 ASD 的病因有因果关系（也可能是精神分裂症）。