Disrupted Social Preference in Early Psychosis: A Longitudinal Multimodal Neuroimaging Study

早期精神病中社会偏好的破坏：一项纵向多模态神经影像学研究

• 批准号: 10256656
• 负责人: Junghee Lee
• 金额: $ 53.29万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256656
• 关键词: Admission activity; Adult; Affect; Aftercare; Age of Onset; Behavior assessment; Behavioral; Brain; Clinical Sciences; Data; Development; Elements; Foundations; Functional Magnetic Resonance Imaging; Glutamates; Human; Impaired cognition; Individual; Intervention; Lead; Learning; Life; Link; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measures; Mediating; Modeling; N-Methyl-D-Aspartate Receptors; N-methyl-D-glutamate; National Institute of Mental Health; Neurosciences; Patient Recruitments; Patients; Phase; Prefrontal Cortex; Process; Protons; Psychoses; Research; Rewards; Rodent; Role; Schizophrenia; Science; Social Functioning; Social Interaction; Stimulus; System; Testing; Theoretical model; Therapeutic Agents; Ventral Striatum; base; cognitive development; cognitive performance; cognitive training; critical period; design; early adolescence; emerging adult; first episode schizophrenia; improved; indexing; interest; multimodality; neuroimaging; preference; programs; psychosocial; psychosocial development; relating to nervous system; response; skills; social; social cognition; social deficits; theories

ABSTRACT Schizophrenia (SZ) is characterized by a severe and debilitating loss of social functioning. Despite considerable efforts to find ways to improve social functioning, little satisfactory progress has been made. The typical age of onset for SZ (i.e., late adolescence / early adulthood) coincides with a period of critical psychosocial development, during which individuals learn to form and maintain relationships, skills that serve as a foundation for successful social interactions throughout adulthood. During this period, dynamic changes also occur in the brain, which could have life-long effects on social functioning. A longitudinal study of individuals early in their course of illness will provide a window into this critical phase of development, allowing us to examine potential mechanisms affecting social functioning in SZ. We recently proposed a theoretical model in which disrupted social preference and glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction are crucial to understanding social dysfunction in SZ. Social preference refers to the bias or tendency for individuals to prioritize processing of social over nonsocial stimuli. This model is based on convergent evidence from developmental science, clinical science, and behavioral neuroscience. This R01 aims to evaluate the above model using a longitudinal multimodal neuroimaging approach applied to seventy- two patients with first-episode SZ and seventy-two demographically matched controls. We will recruit patients immediately after their admission into the UCLA Aftercare Research Program, in which they will receive an intensive psychosocial intervention, including social cognitive training, for 6 months, as part of the Aftercare Program. Patients will be assessed at both baseline and 6 months; controls will be assessed only at baseline. Using functional magnetic resonance imaging (fMRI), we will measure neural activation by contrasting social versus nonsocial reward during a social preference task. Using proton magnetic resonance spectroscopy (1H MRS), we will obtain an index of glutamatergic activity (i.e., glutamate levels). The primary regions of interest for both fMRI and 1H MRS will be the ventral striatum and ventromedial prefrontal cortex. Social cognition and social functioning will also be assessed. With this design, we will determine whether 1) first-episode patients show aberrant neural activation and glutamate levels 2) longitudinal changes in neural activations and glutamate levels are associated with changes in social cognitive performance as patients receive integrated treatments after their first episode. As an exploratory aim, using a multimodal approach integrating fMRI, 1H MRS and behavioral assessment data, we will test associations among disrupted social preference, glutamate levels, and social functioning in patients early in their courses of illness. The findings of this project could provide a much-needed link between social dysfunction and the pathophysiological processes of schizophrenia as well as suggesting directions for potential therapeutic agents for social dysfunction that target the glutamatergic system.

ABSTRACT Schizophrenia (SZ) is characterized by a severe and debilitating loss of social functioning. Despite considerable efforts to find ways to improve social functioning, little satisfactory progress has been made. The typical age of onset for SZ (i.e., late adolescence / early adulthood) coincides with a period of critical psychosocial development, during which individuals learn to form and maintain relationships, skills that serve as a foundation for successful social interactions throughout adulthood. During this period, dynamic changes also occur in the brain, which could have life-long effects on social functioning. A longitudinal study of individuals early in their course of illness will provide a window into this critical phase of development, allowing us to examine potential mechanisms affecting social functioning in SZ. We recently proposed a theoretical model in which disrupted social preference and glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction are crucial to understanding social dysfunction in SZ. Social preference refers to the bias or tendency for individuals to prioritize processing of social over nonsocial stimuli. This model is based on convergent evidence from developmental science, clinical science, and behavioral neuroscience. This R01 aims to evaluate the above model using a longitudinal multimodal neuroimaging approach applied to seventy- two patients with first-episode SZ and seventy-two demographically matched controls. We will recruit patients immediately after their admission into the UCLA Aftercare Research Program, in which they will receive an intensive psychosocial intervention, including social cognitive training, for 6 months, as part of the Aftercare Program. Patients will be assessed at both baseline and 6 months; controls will be assessed only at baseline. Using functional magnetic resonance imaging (fMRI), we will measure neural activation by contrasting social versus nonsocial reward during a social preference task. Using proton magnetic resonance spectroscopy (1H MRS), we will obtain an index of glutamatergic activity (i.e., glutamate levels). The primary regions of interest for both fMRI and 1H MRS will be the ventral striatum and ventromedial prefrontal cortex. Social cognition and social functioning will also be assessed. With this design, we will determine whether 1) first-episode patients show aberrant neural activation and glutamate levels 2) longitudinal changes in neural activations and glutamate levels are associated with changes in social cognitive performance as patients receive integrated treatments after their first episode. As an exploratory aim, using a multimodal approach integrating fMRI, 1H MRS and behavioral assessment data, we will test associations among disrupted social preference, glutamate levels, and social functioning in patients early in their courses of illness. The findings of this project could provide a much-needed link between social dysfunction and the pathophysiological processes of schizophrenia as well as suggesting directions for potential therapeutic agents for social dysfunction that target the glutamatergic system.