Department of Clinical Research Promotion, National Center Hospital, National Center of Neurology and Psychiatry Tokyo, Japan.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo, Japan.
Front Neurosci. 2014 Dec 4;8:395. doi: 10.3389/fnins.2014.00395. eCollection 2014.
Negative symptoms (e.g., decreased spontaneity, social withdrawal, blunt affect) and disturbances of cognitive function (e.g., several types of memory, attention, processing speed, executive function, fluency) provide a major determinant of long-term outcome in patients with schizophrenia. Specifically, motivation deficits, a type of negative symptoms, have been attracting interest as (1) a moderator of cognitive performance in schizophrenia and related disorders, and (2) a modulating factor of cognitive enhancers/remediation. These considerations suggest the need to clarify neurobiological substrates regulating motivation. Genetic studies indicate a role for the monoamine systems in motivation and key cognitive domains. For example, polymorphism of genes encoding catecholamine-O-methyltransferase, an enzyme catabolizing dopamine (DA), affects performance on tests of working memory and executive function in a phenotype (schizophrenia vs. healthy controls)-dependent fashion. On the other hand, motivation to maximize rewards has been shown to be influenced by other genes encoding DA-related substrates, such as DARPP-32 and DA-D2 receptors. Serotonin (5-HT) receptors may also play a significant role in cognitive and motivational disabilities in psychoses and mood disorders. For example, mutant mice over-expressing D2 receptors in the striatum, an animal model of schizophrenia, exhibit both decreased willingness to work for reward and up-regulation of 5-HT2C receptors. Taken together, genetic predisposition related to 5-HT receptors may mediate the diversity of incentive motivation that is impaired in patients receiving biological and/or psychosocial treatments. Thus, research into genetic and neurobiological measures of motivation, in association with 5-HT receptors, is likely to facilitate intervention into patients seeking better social consequences.
阴性症状（例如，自发性降低、社会退缩、情感迟钝）和认知功能障碍（例如，多种类型的记忆、注意力、加工速度、执行功能、流畅性）是精神分裂症患者长期预后的主要决定因素。具体来说，动机缺陷作为一种阴性症状，已引起关注，因为它是（1）精神分裂症和相关障碍认知表现的调节剂，以及（2）认知增强剂/矫正的调节因素。这些考虑表明需要阐明调节动机的神经生物学基础。遗传研究表明单胺系统在动机和关键认知领域中起作用。例如，编码儿茶酚-O-甲基转移酶（一种代谢多巴胺（DA）的酶）的基因多态性，以表型（精神分裂症与健康对照组）依赖的方式影响工作记忆和执行功能测试的表现。另一方面，对最大化奖励的动机已被证明受到其他编码与 DA 相关的底物的基因的影响，例如 DARPP-32 和 DA-D2 受体。5-羟色胺（5-HT）受体也可能在精神分裂症和心境障碍的认知和动机障碍中发挥重要作用。例如，纹状体中过度表达 D2 受体的突变小鼠，一种精神分裂症的动物模型，表现出工作意愿降低和 5-HT2C 受体上调。总之，与 5-HT 受体相关的遗传易感性可能介导接受生物和/或心理社会治疗的患者受损的激励动机的多样性。因此，对与 5-HT 受体相关的动机的遗传和神经生物学测量的研究，可能有助于干预寻求更好社会后果的患者。
