Adolescent Neurodevelopment and Impaired Intrinsic Motivation in Psychosis Risk

青少年神经发育和内在动机受损导致精神病风险

• 批准号: 10320342
• 负责人: DANIEL H WOLF
• 金额: $ 57.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320342
• 关键词: Address; Adolescence; Adolescent; Age; Awareness; Behavioral; Brain; Clinical; Clinical assessments; Cognitive; Cognitive remediation; Complex; Corpus striatum structure; Curiosities; Data; Decision Making; Development; Dimensions; Early Diagnosis; Early identification; Family; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image; Impairment; Individual; Individual Differences; Intervention; Interview; Investigation; Learning; Measures; Mental disorders; Modeling; Motivation; Occupational; Outcome; Participant; Pathologic; Patient Self-Report; Pattern; Pharmaceutical Preparations; Phenotype; Philadelphia; Prevalence; Prevention; Psychiatry; Psychological reinforcement; Psychopathology; Psychoses; Public Health; Punishment; Research; Resistance; Resources; Rest; Rewards; Risk; Risk Factors; Sampling; Schizophrenia; Severities; Societies; Stimulus; Structure; Symptoms; Testing; Time; Ventral Striatum; Work; Youth; brain abnormalities; cognitive performance; cohort; cost; critical period; design; disability; effective therapy; extrinsic motivation; follow-up; functional disability; functional outcomes; gray matter; imaging biomarker; intrinsic motivation; multimodality; neural circuit; neural correlate; neurobehavioral; neurodevelopment; neuroeconomics; neuroregulation; novel; predictive marker; prospective; psychosis risk; psychosocial; recruit; response; reward circuitry; satisfaction; schizophrenia risk; social; targeted treatment; theories; therapy development; visual memory; vulnerable adolescent

Project Summary Intrinsic motivation is the desire for internal satisfactions like curiosity, challenge, and mastery. It depends upon the ability to self-generate reward responses while performing an activity, even in the absence of any external rewards. The proposed study aims to discover the neurodevelopmental abnormalities contributing to impairment of intrinsic motivation in adolescents at risk for psychosis, in order to accelerate future efforts at early detection, treatment, and prevention. Pathological loss of motivation is a key treatment- resistant driver of disability in schizophrenia. Recent research shows that negative symptoms including amotivation often arise in adolescence in those who are vulnerable to psychosis. These negative symptoms can be the first indicators of the illness prodrome, and they tend to persist and cause poor functional outcomes even in those individuals who never convert to frank psychosis. Intrinsic motivation deficits appear to be selectively related to clinical impairment, but they have not been studied in psychosis risk, and the contributory brain abnormalities remain largely unknown. Recent research has shown that motivation deficits in schizophrenia are associated with hypofunction in brain reward circuitry including ventral striatum (VS). This deficit is not only evident in response to monetary reward, but also in response to internal awareness of correct cognitive performance, providing an imaging marker of impaired intrinsic motivation. However, so far no studies have examined any specific measures of intrinsic motivation in psychosis risk, and greater understanding of both intrinsic and extrinsic aspects of motivation will be essential. The proposed five-year study will conduct multilevel phenotyping of motivation deficits at baseline and at 2-year follow-up in youth age 16-23 at risk for psychosis, leveraging and extending resources from the Philadelphia Neurodevelopmental Cohort. This work will characterize the neurodevelopmental pathophysiology of amotivation and develop predictive biomarkers, with the ultimate goal of ameliorating disabling amotivation in psychosis risk. The specific aims are: 1) To characterize neural circuitry responsive to intrinsic reinforcement in adolescents; 2) To characterize brain circuit abnormalities associated cross-sectionally with amotivation severity in psychosis risk; and 3) To identify longitudinal relationships between neurodevelopment and amotivation in psychosis risk.

项目摘要 内在动机是对内部满足的渴望，如好奇心，挑战和掌握。它 取决于在执行活动时自我产生奖励反应的能力，即使在没有 任何外部奖励。这项研究旨在发现神经发育异常 有助于精神病风险青少年内在动机的损害，以加速 未来的努力，在早期发现，治疗和预防。病理性的动力丧失是一种关键的治疗方法- 精神分裂症中的抵抗性残疾驱动因素。最近的研究表明，消极的症状，包括 那些易患精神病的人往往在青春期出现动力丧失。这些负面症状 可能是疾病前驱症状的第一个指标，它们往往会持续存在并导致不良的功能结局 即使是那些从未转变为精神病的人。内在动机缺陷似乎是 选择性地与临床损害相关，但尚未在精神病风险中进行研究， 大脑异常在很大程度上仍然未知。最近的研究表明， 精神分裂症与包括腹侧纹状体（VS）在内大脑奖赏回路功能减退有关。这 赤字不仅在对金钱奖励的反应中很明显，而且在对正确的内部意识的反应中也很明显。 认知表现，提供受损的内在动机的成像标记。然而，到目前为止， 研究已经检查了精神病风险内在动机的任何具体措施， 理解动机的内在和外在方面是必不可少的。拟议五年 一项研究将在基线和2年随访时对年轻人的动机缺陷进行多级表型分析 16-23岁有精神病风险，利用和扩展费城神经发育中心的资源 队列。这项工作将描述神经发育的病理生理学的失动和发展 预测性生物标志物，最终目标是改善精神病风险中的失能动力。的 具体目标是：1）表征青少年对内在强化反应的神经回路; 2） 表征与精神病风险中的失动严重程度相关的脑回路异常; （3）确定精神病风险中神经发育和动机丧失之间的纵向关系。

项目成果

Two Neuroanatomical Signatures in Schizophrenia: Expression Strengths Over the First 2 Years of Treatment and Their Relationships to Neurodevelopmental Compromise and Antipsychotic Treatment.

• DOI: 10.1093/schbul/sbad040
• 发表时间: 2023-07-04
• 期刊: SCHIZOPHRENIA BULLETIN
• 影响因子: 6.6
• 作者: du Plessis, Stefan;Chand, Ganesh B.;Erus, Guray;Phahladira, Lebogang;Luckhoff, Hilmar K.;Smit, Retha;Asmal, Laila;Wolf, Daniel H.;Davatzikos, Christos;Emsley, Robin
• 通讯作者: Emsley, Robin

Asymmetric signaling across the hierarchy of cytoarchitecture within the human connectome.

• DOI: 10.1126/sciadv.add2185
• 发表时间: 2022-12-14
• 期刊: Science advances
• 影响因子: 13.6