The advent of non-invasive connectivity-oriented neuroimaging methods has shed new light onto the inner workings of the brain. The brain's functional and structural connectome play key roles in regulating the pathways from genes to neural systems to mental illnesses. Along these pathways, we hypothesize that abnormal activity in the innate stress-immune pathways has a major contribution to the brain connectome disruption in early stage of schizophrenia spectrum disorder and to its clinical consequence. The project proposes to extend the Connectome Project in Mental Illness to characterize brain circuitry and its relation to stress-immune axis dysfunction in early stage of schizophrenia spectrum disorder in China. We propose a longitudinal study in a large sample of patients that aims to overcome the heterogeneity in the relationship between mental illness and stress-immune-connectome axis, a well-recognized barrier to advancing research and treatment. We will recruit 500 patients with schizophrenia spectrum disorders within five years of disease onset. They will be assessed using modern chronic stress and acute psychological stress laboratory paradigms to define the stress biomarkers at baseline. The patients will be compared with 250 age and sex matched healthy controls. The collaboration leverages the clinical stress research expertise by the U.S. partner and the the clinical immunology research expertise in schizophrenia by the Chinese partner. The proposed study also builds on our ongoing work using acute and chronic stress paradigms to understand how stress is linked to brain structural and functional connectome in schizophrenia spectrum disorders. This novel proposition in U.S. and Chinese mental health research field is strongly supported by preliminary data. The ability to apply the cutting edge connectome protocol using the advanced research designated scanner in Beijing will also enhance our ability to use multimodal imaging tools to aid biologically based heterogeneity reduction. Together, this study will generate actionable strategies to treat and prevent brain connectome deterioration and facilitate clinical recovery after psychosis onset.

Public Health Relevance

The U.S. - China Collaboration project will collect data from a large group of schizophrenia spectrum disorder patients in their early stage of disease. The project aims to study how stress and immune adaptive function or dysfunction may impact brain circuitry and disease progression or recovery, so that doctors can provide more effective prevention and treatment options to these patients in the future.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hillefors, MI
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Schools of Medicine
United States
Zip Code
Fan, Fengmei; Zou, Yizhuang; Tan, Yunlong et al. (2017) Computerized cognitive remediation therapy effects on resting state brain activity and cognition in schizophrenia. Sci Rep 7:4758
Ryan, Meghann; Kochunov, Peter; Rowland, Laura M et al. (2017) Lipid Metabolism, Abdominal Adiposity, and Cerebral Health in the Amish. Obesity (Silver Spring) 25:1876-1880
Chiappelli, Joshua; Kochunov, Peter; Savransky, Anya et al. (2017) Allostatic load and reduced cortical thickness in schizophrenia. Psychoneuroendocrinology 77:105-111
Savransky, Anya; Chiappelli, Joshua; Rowland, Laura M et al. (2017) Fornix Structural Connectivity and Allostatic Load: Empirical Evidence From Schizophrenia Patients and Healthy Controls. Psychosom Med 79:770-776
Kochunov, Peter; Coyle, Thomas R; Rowland, Laura M et al. (2017) Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia. JAMA Psychiatry 74:958-966
Bruce, H A; Kochunov, P; Paciga, S A et al. (2017) Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia. Genes Brain Behav 16:515-521