Olfactory and facial markers of developmental risk for psychosis in 22q11 deletion syndrome

22q11 缺失综合征精神病发育风险的嗅觉和面部标记

• 批准号: 10023944
• 负责人: PAUL J MOBERG
• 金额: $ 74.04万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10023944
• 关键词: 22q11.2; 3-Dimensional; Acoustic Rhinometry; Behavioral; Biometry; Body part; Brain region; Characteristics; Classification; Clinical; Craniofacial Abnormalities; Data; Development; DiGeorge Syndrome; Diffuse; Dimensions; Distress; Dysmorphology; Ear; Etiology; Event; Exhibits; Eye; Face; Functional disorder; Genetic Diseases; Genetic Risk; Geometry; Head; Image; Impaired cognition; Impairment; Individual; Lead; Machine Learning; Magnetic Resonance Imaging; Mandible; Measures; Medial; Mental disorders; Minor; Modeling; Morphology; Nasal cavity; Neurobiology; Nose; Odors; Olfactory Cortex; Olfactory Pathways; Oral cavity; Patients; Performance; Peripheral; Phenotype; Process; Psychiatry; Psychophysics; Psychotic Disorders; Public Health; Research; Risk; Sampling; Schizophrenia; Severities; Smell Perception; Societies; Structural defect; Structure; Symptoms; Syndrome; Techniques; Temporal Lobe; Testing; Three-Dimensional Imaging; Work; Youth; associated symptom; base; behavior measurement; brain dysfunction; clinically relevant; cohort; cost; effective therapy; functional outcomes; genetic disorder diagnosis; high risk; improved; innovation; machine learning algorithm; microdeletion; multilevel analysis; neurodevelopment; neuromechanism; neuropathology; olfactory bulb; olfactory sulcus; precision medicine; psychotic symptoms; resilience; trait

Project Summary: 22q11.2 deletion syndrome (22q11DS) is associated with an increased risk for psychiatric disorders, including psychosis with similar symptoms to individuals with idiopathic schizophrenia (SZ), and about 1-2% of cases of idiopathic SZ have 22q11.2 deletions. Thus, targeted approaches detailing specific brain dysfunction in 22q11DS may elucidate critical neural mechanisms in psychosis. Specifically, approaches that capture abnormalities common to individuals at-risk for psychosis and with a genetic risk to psychosis, such as 22q11DS, may help explain risk and resilience for psychosis. Minor physical anomalies (MPAs) are phenotypic abnormalities of aberrant development. MPAs include subtle abnormalities of morphological structures encompassing numerous body parts including eyes, ears, mouth and head. Abnormalities of the face and head likely represent a disruption of early embryologic development, including the olfactory system and facial morphology, making these promising entry points for understanding neurodevelopmental neuropathology associated with 22q11DS and psychosis In this study, we seek to compare 1) measures of olfactory function; 2) structural abnormalities of the olfactory system and 3) structural abnormalities of the face in a large cohort of patients with 22q11DS (n=100), including those with and without psychosis, to typically developing (TD) individual. Finally, we will employ machine learning algorithms to select features that best differentiate 22q11DS+ from 22q11DS- and use those features to classify individual with idiopathic risk for psychosis (PS). In addition, analyses will leverage recent advances in machine learning to predict salient features associated with dimensional measures of psychosis. We believe this innovative approach can significantly advance our understanding of the etiology of psychosis and provide advances to precision medicine in psychiatry. Through the proposed multi-level analysis, this innovative research will provide a substantial advance in our understanding of the neurodevelopmental substrates of psychosis.

项目总结：22q11.2缺失综合征（22q11DS）与精神疾病风险增加相关