The first treatments showing effectiveness for some psychiatric disorders, such as lithium for bipolar disorder and chlorpromazine for schizophrenia, were discovered by accident. Currently, psychiatric drug design is seen as a scientific enterprise, limited though it remains by the complexity of brain development and function. Relatively few novel and effective drugs have, however, been developed for many years. The purpose of this article is to demonstrate how evolutionary biology can provide a useful framework for psychiatric drug development. The framework is based on a diametrical nature of autism, compared with psychotic-affective disorders (mainly schizophrenia, bipolar disorder and depression). This paradigm follows from two inferences: (i) risks and phenotypes of human psychiatric disorders derive from phenotypes that have evolved along the human lineage and (ii) biological variation is bidirectional (e.g. higher vs lower, faster vs slower, etc.), such that dysregulation of psychological traits varies in two opposite ways. In this context, the author review the evidence salient to the hypothesis that autism and psychotic-affective disorders represent diametrical disorders in terms of current, proposed and potential psychopharmacological treatments. Studies of brain-derived neurotrophic factor, the PI3K pathway, the NMDA receptor, kynurenic acid metabolism, agmatine metabolism, levels of the endocannabinoid anandamide, antidepressants, anticonvulsants, antipsychotics, and other treatments, demonstrate evidence of diametric effects in autism spectrum disorders and phenotypes compared with psychotic-affective disorders and phenotypes. These findings yield insights into treatment mechanisms and the development of new pharmacological therapies, as well as providing an explanation for the longstanding puzzle of antagonism between epilepsy and psychosis. Lay Summary: Consideration of autism and schizophrenia as caused by opposite alterations to brain development and function leads to novel suggestions for pharmacological treatments.

中文翻译：

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自闭症和精神情感障碍的比较精神药理学提出了新的治疗目标。

第一个对某些精神疾病有效的治疗方法，例如锂盐治疗双相情感障碍和氯丙嗪治疗精神分裂症，都是偶然发现的。目前，精神科药物设计被视为一项科学事业，尽管它仍然受到大脑发育和功能的复杂性的限制。然而，多年来开发出的新型有效药物相对较少。本文的目的是展示进化生物学如何为精神科药物开发提供有用的框架。该框架基于自闭症与精神情感障碍（主要是精神分裂症、躁郁症和抑郁症）的直接性质。这一范式源自两个推论：（i）人类精神疾病的风险和表型源自沿着人类谱系进化的表型；（ii）生物变异是双向的（例如更高与更低、更快与更慢等），例如心理特征的失调以两种相反的方式变化。在这种背景下，作者回顾了这一假设的重要证据，即自闭症和精神情感障碍代表了当前、拟议和潜在的精神药理学治疗的直接疾病。对脑源性神经营养因子、PI3K 通路、NMDA 受体、犬尿酸代谢、胍丁胺代谢、内源性大麻素 anandamide 水平、抗抑郁药、抗惊厥药、抗精神病药和其他治疗的研究，证明了自闭症谱系障碍和表型中直接影响的证据与精神情感障碍和表型相比。这些发现为治疗机制和新药理学疗法的开发提供了深入的见解，并为癫痫和精神病之间长期存在的对抗难题提供了解释。简单总结：自闭症和精神分裂症是由大脑发育和功能的相反改变引起的，这为药物治疗提出了新的建议。