Neurodevelopment of Mesolimbic Afferents in Healthy Adolescents and First-Episode Psychosis

健康青少年和首发精神病中脑边缘传入神经发育

• 批准号: 9384024
• 负责人: Vishnu Pradeep Murty
• 金额: $ 4.15万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-09 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9384024
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Age; Age-Years; Animal Model; Antipsychotic Agents; Award; Behavior; Biological Assay; Caregivers; Chronic; Clinical; Communities; Data Analyses; Deterioration; Development; Diffusion; Disease; Dopamine; Economics; Emotional; Etiology; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Grant; Hippocampus (Brain); Human; Individual; Intervention; Investigation; K-Series Research Career Programs; Knowledge; Learning; Measures; Medial; Mediating; Mentors; Modeling; Nature; Participant; Pathology; Pathway Analysis; Patients; Pharmaceutical Preparations; Phase; Play; Population; Positron-Emission Tomography; Prefrontal Cortex; Psychopathology; Psychotic Disorders; Recruitment Activity; Regulation; Research; Research Domain Criteria; Research Training; Rest; Rewards; Risk; Role; Sampling; Schizophrenia; Signal Transduction; Substantia nigra structure; System; Systems Development; Techniques; Testing; Time; Training; Translating; Translations; Universities; Ventral Tegmental Area; Visit; Work; base; clinical predictors; cognitive neuroscience; data archive; dopamine system; dopaminergic neuron; emerging adult; first episode psychosis; follow-up; insight; lens; mesolimbic system; multimodality; neurodevelopment; neuroimaging; neuroimaging marker; neuroregulation; novel; phenomenological models; programs; relating to nervous system; remediation; social; spectrograph; translational neuroscience; white matter; young adult

Project Summary/Abstract The objective of this Career Development Award is to support new mentored training in cognitive neuroscience studies of dopamine-related function in healthy adolescents and first-episode psychosis, as the candidate begins an independent research program. Psychosis is a devastating illness that afflicts ~3% of the world’s population, and has sever economic and social/emotional consequences for both patients and their caregivers. Prior research has implicated deficits in dopamine systems in both the etiology and pathology of the disorder, and thus remediation of this system has been a prominent target for intervention. Although these deficits have been well documented, open questions remains as to how and why these deficits emerge. Prominent models of psychosis have implicated aberrant development of neural systems regulating the activation of dopamine systems. However, very little research has investigated how these regulatory systems develop in normative populations; let alone how deviations from normative development may be implicated in psychosis. Thus, a full understanding of psychosis necessitates a characterization of dopamine-related networks in healthy adolescence and deviations from these trajectories in psychosis. These findings will provide insight into determinants of risk for conversion from a developmental perspective and in turn the timing of interventions. The proposed award will build upon the candidate’s prior training in cognitive neuroscience, to extend this knowledge into the domain of normative development in adolescents and aberrant development in psychosis within dopamine-related networks. Aim 1 will investigate the normative development of neural systems regulating engagement of the ventral tegmental area and substantia nigra, the core of the mesolimbic dopamine system, using multimodal neuroimaging. These developmental neuroimaging markers will then be associated with direct and indirect measures of dopamine to assess how they relate to dopaminergic function. Aim 2 will evaluate how individuals with first-episode psychosis deviate from the normative trajectories characterized in Aim 1, and further probe how these deviations relate to anti-psychotic medication status. Finally, Aim 3 will have first-episode patients return for a 2-year follow-up to characterize how the clinical course of psychosis relates to early markers of dopamine-related dysfunction. Mentored training will compliment the candidate’s expertise in neuroimaging of dopamine-related circuits in healthy adults. Paralleling the proposed research, training will focus on the candidate gaining expertise in conducting neuroimaging studies in adolescent (Aim 1) and psychosis populations (Aim 2,3). Further, the candidate will gain expertise in the translation of animal models of behavior in adolescent and psychosis population, with a focus on understanding the nature of homology across multiple species (Aims 1-3). Finally, the candidate will gain expertise in experimental techniques associated with studying neurodevelopment (e.g., longitudinal data analysis; Aims 1-3), psychosis (e.g., adjustment for antipsychotic medication, characterizing clinical phenomenology; Aims 2-3), and translational neuroscience (e.g., integration of direct/indirect measures of dopamine; Aim 3). The candidate has recruited a mentoring team with expertise in all of the above domains led by mentor Dr. Bea Luna, an expert in adolescent development, and co-mentor Deanna Barch, an expert in neuroimaging in psychosis populations. Further, the candidate will take advantage of the known strengths of the schizophrenia and adolescent research communities, as well as the emphasis on cross-species translation at the University of Pittsburgh. The proposed research will offer novel insight into dopamine dysfunction in psychosis through the lens of adolescent neurodevelopment. Further, the training will lay the foundation for an independent research program assaying the neurodevelopmental of neuromodulatory systems in psychosis. !

项目总结/文摘