期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 1, 页码 267-286出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2310-14.2015
关键词
computational modeling; first episode; hyperconnectivity; longitudinal; prefrontal cortex; schizophrenia
资金
- National Natural Science Foundation [81030027, 81227002, 81220108013]
- National Key Technologies R and D Program [2012BAI01B03]
- Program for Changjiang Scholars and Innovative Research Team in University of China [IRT1272]
- National Institutes of Health [DP5OD012109-02]
- National Institute on Alcohol Abuse and Alcoholism [2P50AA012870-11, MH096801, R01-MH062349, T32GM 007205]
- National Alliance for Research on Schizophrenia and Depression
- Fulbright Foundation
- Yale Center for Clinical Investigation
Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for hypoconnectivity. At the whole-brain level, we observed hyperconnectivity around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications.
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