Psychosis risk variants and cognitive control in clinically-referred youth

临床转介青少年的精神病风险变异和认知控制

• 批准号: 9252794
• 负责人: ALYSA E DOYLE
• 金额: $ 7.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252794
• 关键词: Alleles; Behavioral Genetics; Biology; Calcium Channel; Categories; Clinical; Clinical Research; Cognition; Cognition Disorders; Cognitive; Collaborations; Collection; Communication; Complex; Data; Data Analyses; Data Collection; Data Set; Development; Diagnosis; Diagnostic; Dissection; Early Intervention; Evaluation; Family Study; Fostering; Funding; General Hospitals; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genetic Risk; Genetic study; Genome Scan; Genotype; Goals; Health; Human Genetics; Impaired cognition; Impairment; Individual; Institutes; Investigation; Leadership; Link; Literature; Maintenance; Maps; Massachusetts; Measurable; Measures; MicroRNAs; Modeling; Molecular Genetics; Mutation; National Institute of Mental Health; Patients; Pattern; Performance; Phenotype; Predisposition; Prospective Studies; Psychiatry; Psychopathology; Psychotic Disorders; Research; Research Domain Criteria; Risk; Role; Sampling; Short-Term Memory; Signal Transduction; Structure; Synapses; Taxonomy; Testing; Twin Multiple Birth; Twin Studies; Variant; Work; Youth; base; biological systems; cognitive control; cognitive system; cognitive testing; cohort; disorder risk; effective intervention; follow-up; genetic variant; genome-wide; improved; neuropsychiatry; novel; programs; response; risk variant; severe mental illness; synaptic function; targeted treatment; trait; voltage

 DESCRIPTION (provided by applicant): Family, twin and prospective studies of psychosis provide strong but indirect evidence that impaired cognitive control is a manifestation of underlying genetic risk for this devastating form of psychopathology. Findings from recent, large-scale genomewide studies now offer the chance to extend this line of investigation directly to molecular genetic data. In response to PAR-14-007, we aim to capitalize on an available data set to pursue such analyses. Specifically, we will examine emerging psychosis-relevant genetic variants in relation to three constructs (working memory, inhibition and goal maintenance) that overlap with the domain of cognitive control, as defined in NIMH's Research Domain Criteria (RDoC). RDoC was developed precisely to encourage investigation of genetic advances such as these in relation to dimensional traits unconstrained by conventional diagnoses. Currently, we are near-completion of a pilot clinical research cohort of youth uniquely-suited to such investigation. In this sample, subjects are ascertained, regardless of diagnosis, as consecutive referrals for neuropsychiatric evaluations that include cognitive assessment. Using these data in this R03, we will test the hypothesis that, across diagnostic boundaries, a greater burden of common genetic variants that confer risk for psychosis associates with greater impairment in our three aspects of cognitive control. Second, we will test the hypothesis that variation in psychosis-relevant gene sets that support synaptic communication and plasticity will similarly associate with variation in these aspects of cognitive control. Based on our preliminary data, we expect that our findings will advance the core tenets of RDoC and suggest that genetic risk for psychosis operates beyond conventional diagnostic boundaries and can be detected in relation to cognitive control phenotypes measurable in youth. These data will further help to link these cognitive constructs to particular biological systems. As such, these data will allow us to refine cognitive phenotypes we investigate as we enlarge our sample (under separate funding) and work to improve pathophysiologically-based models of the unfolding of genetic risk for psychosis. Eventually, such findings could facilitate earlier and more effective interventions in youth at risk for severe neuropsychiatric illness.



项目成果

Cross-Disorder Cognitive Impairments in Youth Referred for Neuropsychiatric Evaluation.

• DOI: 10.1017/s1355617717000601
• 发表时间: 2018-01
• 期刊: Journal of the International Neuropsychological Society : JINS
• 作者: Doyle AE;Vuijk PJ;Doty ND;McGrath LM;Willoughby BL;O'Donnell EH;Wilson HK;Colvin MK;Toner DC;Hudson KE;Blais JE;Ditmars HL;Faraone SV;Seidman LJ;Braaten EB
• 通讯作者: Braaten EB