The goal of this Mentored Career Development Award proposal is to provide Dr. Fei Wang advanced training in integrating multidisciplinary research methods, including multimodal neuroimaging techniques and molecular genetics, to study the frontotemporal neural system involved in bipolar disorder (BD) and schizophrenia (SZ). Dr. Wang's rich background implementing multimodal neuroimaging techniques and molecular genetics in the study of BD and SZ makes her uniquely suited to conduct this work. Utilizing the aforementioned techniques, she proposes to conduct direct comparisons between individuals with BD, SZ and healthy comparison participants necessary to elucidate the distinct pathophyisology involved in each disorder. Emerging data in BD and SZ simultaneously support overlapping susceptibility to genes that regulate the development of frontotemporal neural systems as well as features offrontotemporalabnormalities that are distinct to each disorder. Frontotemporal neural system abnormalities in BD are centered in more ventral structures including ventral prefrontal cortex and amygdala;while deficits in more dorsal areas are implicated in SZ including dorsal lateral prefrontal cortex and the hippocampus. Furthermore, she will investigate the differential impact of genetic variation in neuregulin 1 and its receptor ErbB4 on the frontotemporal neural systems in BD and SZ. Training components will include supervised research, formal coursework, and advanced training in multimodal neuroimaging techniques and molecular genetics. The multidisciplinary nature of this project, conducted under the mentorship of Drs. Hilary Blumberg, John Krystal, R. Todd Constable and Joel Gelernter, in collaboration with experts in BD and SZ research, neuroimaging analysis, molecular genetics, molecular modeling strategies for neuroimaging studies and clinical neuroscience will provide a valuable opportunity for the candidate to address issues regarding the effects of genetic variation on the frontotemporal neural systems in BD and SZ. The project will provide the vital support and training necessary for Dr. Wang to become an independent investigator expert in the application of multimodal neuroimaging and molecular genetics to identify underlying frontotemporal neural system abnormalities in BD and SZ.

Public Health Relevance

This project aims to investigate differences in the distribution of brain abnormalities in bipolar disorder and schizophrenia and to determine which genes may contribute to the distinct distributions. This work will enhance our understanding of the causes of these disorders, our ability to detect the disorders early and to develop novel and more effective treatments. Finally, it will enable the training of an investigator uniquely suited to conduct this work by combining advanced research techniques from various fields of science.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Wynne, Debra K
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Yale University
Schools of Medicine
New Haven
United States
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Najt, Pablo; Wang, Fei; Spencer, Linda et al. (2016) Anterior Cortical Development During Adolescence in Bipolar Disorder. Biol Psychiatry 79:303-10
Geng, Haiyang; Wu, Feng; Kong, Lingtao et al. (2016) Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression. PLoS One 11:e0148345
Rich, Alyson M; Cho, Youngsun T; Tang, Yanqing et al. (2016) Amygdala volume is reduced in early course schizophrenia. Psychiatry Res 250:50-60
Tang, Yanqing; Chen, Kaiyuan; Zhou, Yifang et al. (2015) Neural activity changes in unaffected children of patients with schizophrenia: A resting-state fMRI study. Schizophr Res 168:360-5
Liu, Jie; Ren, Ling; Womer, Fay Y et al. (2014) Alterations in amplitude of low frequency fluctuation in treatment-naïve major depressive disorder measured with resting-state fMRI. Hum Brain Mapp 35:4979-88
Liu, Hu; Tang, Yanqing; Womer, Fay et al. (2014) Differentiating patterns of amygdala-frontal functional connectivity in schizophrenia and bipolar disorder. Schizophr Bull 40:469-77
Xu, Ke; Liu, Hu; Li, Huanhuan et al. (2014) Amplitude of low-frequency fluctuations in bipolar disorder: a resting state fMRI study. J Affect Disord 152-154:237-42
Zuo, Lingjun; Wang, Kesheng; Wang, Guilin et al. (2014) Common PTP4A1-PHF3-EYS variants are specific for alcohol dependence. Am J Addict 23:411-4
Anticevic, Alan; Tang, Yanqing; Cho, Youngsun T et al. (2014) Amygdala connectivity differs among chronic, early course, and individuals at risk for developing schizophrenia. Schizophr Bull 40:1105-16
Kong, Lingtao; Chen, Kaiyuan; Womer, Fay et al. (2013) Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder. J Psychiatr Res 47:733-9

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