多巴胺在精神分裂症阳性症状中的心理机制：新近理论和研究进展

Psychological mechanisms of dopamine in psychotic symptoms of schizophrenia: Recent theoretical and empirical advances

精神分裂症是造成个人和社会巨大经济负担的中枢神经系统疾病之一,病因至今未明.由于还原论在科研领域的指导作用,人们过多地重视了由基因、分子及受体水平得到的发现去解释该疾病的发病机制.科学家们倾向于通过基因、分子及受体水平的研究结果去解释该病的发病机制.虽然该病是在中枢神经系统障碍的这一微观水平上产生的,但临床的诊断和治疗评定都是根据患者的行为表现这一宏观层面做出的.因此,要更全面地认识精神分裂症,研究者们需要有一套以基本的神经科学理论为基础的心理学理论来阐明该病发生发展中出现的许多现象,同时结合分子水平的研究进展更好地探究本病的发病机制.本文将以该病的妄想和幻觉这阳性症状为主线,选择性地阐述多巴胺神经递质系统在精神分裂症的病因、病理生理学和药物治疗学中的作用及相关神经系统功能的变化,并进一步用心理学的理论来诠释这些现象发生的原因.我们将重点叙述由Shitij Kapur提出的多巴胺-动机突显学说,并结合本实验室在条件反射躲避动物模型实验中的行为药理学研究结果对该理论进行深化和支持.文中介绍的这一学说将分子水平观察到的变化和行为改变彼此之间有机联系起来,强调了精神分裂症患者中枢神经系统存在多巴胺功能紊乱,导致了动机突显这一心理过程的异常,进而引起了患者阳性症状的出现.抗精神分裂症药物正是通过阻断多巴胺递质系统,抑制了异常的动机突显过程,从而改善了患者的症状.希望读者通过阅读本文能够对精神分裂症和多巴胺系统功能异常之间的关系有一个框架性的认识,从多巴胺分子水平和心理学的变化的角度更好地理解精神分裂症的发病原因、药物治疗机理、动物模型研究进展.

Schizophrenia is one of the most severe neuropsychiatric disorders that exert a huge financial burden on individuals and societies. Its etiology is still unknown. Due to the influence of the dominant reductionist approach in this field, much research has been devoted to the studies of the genes, molecules and neuroreceptors and their possible contributions to the development of schizophrenia. Although schizophrenia is considered as a brain disorder, its diagnosis and evaluation of symptom improvement are all based on behavioral observations. Therefore, in order to gain a complete understanding of schizophrenia, we need a psychological theory rooted in basic neurobiology to explain various symptoms of schizophrenia. The present paper focuses on the delusions and hallucinations—two main positive symptoms of schizophrenia—and attempts to delineate the roles of dopamine in the etiology, pathophysiology, and psychopharmacological treatment of schizophrenia and further discuss how these symptoms arise from a psychological perspective. We present findings from our animal psychopharmacology work using the conditioned avoidance response model in the framework of the motivational salience hypothesis proposed by Shitij Kapur. We elaborate on how this hypothesis explains changes at the molecular level （e.g. dopamine） leading to the changes at the behavioral level （e.g. psychosis）. It is thought that hyperactivity of dopamine neurotransmission causes excess incentive learning （e.g., hyperactivity of associations of thoughts） and heightened motivational salience of stimuli （e.g., thoughts, actions, etc.）, which generate many ＂erroneous＂ conclusions in the form of delusions or hallucinations. Antipsychotic drugs are supposed to correct the hyperdoperminergic state in which psychotic beliefs are generated by halting incentive learning or weakening aberrantly heightened salience of psychosis. From this paper, we hope that readers will have a better understanding of the roles of dopamine in the etiology and treatment effects of schizophrenia at the molecular and psychological levels and how animal work can inform psychological mechanisms involved in the development of psychosis.