Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia

精神分裂症动机缺失的定量行为和影像表型

• 批准号: 9070768
• 负责人: DANIEL H WOLF
• 金额: $ 40万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-05 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070768
• 关键词: Adult; Anhedonia; Animal Experimentation; Animal Model; Animals; Anterior; Antipsychotic Agents; Behavior; Behavioral; Biological Markers; Biology; Brain; Brain Diseases; Clinical; Clinical assessments; Complex; Data; Delusions; Development; Disease; Emotional; Emotions; Family; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Hallucinations; Health; Human; Image; Individual; Interview; Investigation; Laboratories; Measures; Mental disorders; Modeling; Motivation; Pattern; Pharmaceutical Preparations; Phenotype; Prevention; Process; Psychiatry; Quality of life; Research; Rewards; Risk; Role; Sampling; Schizophrenia; Severities; Societies; Staging; Symptoms; System; Techniques; Testing; Therapeutic; Therapeutic Human Experimentation; Time; Translational Research; Translations; Validation; Variant; Ventral Striatum; Work; behavior measurement; brain abnormalities; brain behavior; cost; disability; discount; discounting; drug development; effective therapy; functional disability; hedonic; motivated behavior; neural circuit; neurobehavioral; neuroimaging; novel; pleasure; prodromal psychosis; relating to nervous system; response; social

DESCRIPTION (provided by applicant): The proposed study aims to discover the neural circuit abnormalities contributing to amotivation in schizophrenia, and identify quantitative behavioral and imaging measures of amotivation that can accelerate future translational and therapeutic research. A pathological loss of motivation is one of the "negative symptoms" of schizophrenia, which involve deficits in emotional and social capacities. Together with other negative symptoms such as anhedonia (reduced pleasure), asociality (reduced social drive), and reduced expressivity, amotivation contributes strongly to the disability caused by schizophrenia. Unlike positive symptoms (hallucinations, delusions) which are generally responsive to antipsychotic medications, negative symptoms including amotivation respond poorly to current treatments, and therefore constitute a major unmet therapeutic need in psychiatry. Despite this importance, amotivation in schizophrenia has been understudied and the brain abnormalities causing this deficit remain largely unknown. Validation and application of laboratory motivation paradigms in schizophrenia has lagged behind research in hedonic and emotion- processing deficits, and narrowing this gap is a major aim of this proposal. Over four years, the proposed study will evaluate motivation in 80 adults with schizophrenia with a wide range of negative symptoms, as well as 40 healthy control subjects. The specific aims are: 1) To quantify motivational deficits in schizophrenia using translational laboratory tasks, 2) To identif neural circuit dysfunction associated with motivation deficits in schizophrenia, and 3) To define a complex whole-brain phenotype predicting amotivation severity. To achieve these aims we will apply novel behavioral and functional imaging tasks together with advanced multivariate pattern analysis techniques. This study will provide a detailed brain-behavior pattern predicting amotivation severity which will help advance the understanding, treatment, and prevention of schizophrenia.

描述（由申请人提供）：拟议的研究旨在发现有助于精神分裂症失动的神经回路异常，并确定可加速未来转化和治疗研究的失动的定量行为和成像测量。病理性动机丧失是精神分裂症的“阴性症状”之一，涉及情感和社交能力的缺陷。与其他负面症状，如快感缺乏（减少的快乐），社会性（减少的社会驱动力），和减少的表达，动机强烈有助于精神分裂症引起的残疾。与通常对抗精神病药物有反应的阳性症状（幻觉、妄想）不同，阴性症状（包括失动）对当前治疗的反应较差，因此构成精神病学中主要未满足的治疗需求。尽管这一重要性，精神分裂症的动机已经研究不足，大脑异常导致这种赤字仍然在很大程度上未知。精神分裂症的实验室动机范式的验证和应用已经落后于享乐和情绪处理缺陷的研究，缩小这一差距是本提案的主要目的。在四年的时间里，这项拟议中的研究将评估80名患有精神分裂症的成年人的动机，以及40名健康对照受试者。具体目标是：1）使用翻译实验室任务量化精神分裂症的动机缺陷，2）识别与精神分裂症动机缺陷相关的神经回路功能障碍，3）定义一个 复杂的全脑表型预测失动的严重程度。为了实现这些目标，我们将应用新的行为和功能成像任务与先进的多元模式分析技术。这项研究将提供一个详细的脑行为模式预测动机严重程度，这将有助于促进理解，治疗和预防精神分裂症。

项目成果

Causes of death and clinical characteristics of 34 patients with Mucopolysaccharidosis II in Taiwan from 1995-2012.

• DOI: 10.1186/s13023-016-0471-6
• 发表时间: 2016-06-27
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Lin HY;Chuang CK;Huang YH;Tu RY;Lin FJ;Lin SJ;Chiu PC;Niu DM;Tsai FJ;Hwu WL;Chien YH;Lin JL;Chou YY;Tsai WH;Chang TM;Lin SP
• 通讯作者: Lin SP

Schizophrenia Imaging Signatures and Their Associations With Cognition, Psychopathology, and Genetics in the General Population.

• DOI: 10.1176/appi.ajp.21070686
• 发表时间: 2022-09
• 期刊: AMERICAN JOURNAL OF PSYCHIATRY
• 影响因子: 17.7
• 作者: Chand, Ganesh B.;Singhal, Pankhuri;Dwyer, Dominic B.;Wen, Junhao;Erus, Guray;Doshi, Jimit;Srinivasan, Dhivya;Mamourian, Elizabeth;Varol, Erdem;Sotiras, Aristeidis;Hwang, Gyujoon;Dazzan, Paola;Kahn, Rene S.;Schnack, Hugo G.;Zanetti, Marcus, V;Meisenzahl, Eva;Busatto, Geraldo F.;Crespo-Facorro, Benedicto;Pantelis, Christos;Wood, Stephen J.;Zhuo, Chuanjun;Shinohara, Russell T.;Shou, Haochang;Fan, Yong;Koutsouleris, Nikolaos;Kaczkurkin, Antonia N.;Moore, Tyler M.;Verma, Anurag;Calkins, Monica E.;Gur, Raquel E.;Gur, Ruben C.;Ritchie, Marylyn D.;Satterthwaite, Theodore D.;Wolf, Daniel H.;Davatzikos, Christos
• 通讯作者: Davatzikos, Christos

Cardiac features and effects of enzyme replacement therapy in Taiwanese patients with Mucopolysaccharidosis IVA.

• DOI: 10.1186/s13023-018-0883-6
• 发表时间: 2018-08-29
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Lin HY;Chen MR;Lin SM;Hung CL;Niu DM;Chuang CK;Lin SP
• 通讯作者: Lin SP

Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta.

• DOI: 10.1186/s13023-015-0370-2
• 发表时间: 2015-12-01
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Lin HY;Chuang CK;Su YN;Chen MR;Chiu HC;Niu DM;Lin SP
• 通讯作者: Lin SP