Neighborhood social fragmentation in relation to impaired mismatch negativity among youth at clinical high risk for psychosis and healthy comparisons

Neuropsychopharmacology. 2025 Apr 2. doi: 10.1038/s41386-025-02093-4. Online ahead of print.

Abstract

Impairments in mismatch negativity (MMN) are well-established in schizophrenia and have been observed in youth at clinical high-risk for psychosis (CHR-P). Prior animal studies have shown that social isolation may be related to neurobiological changes, including reduced MMN-like responses and schizophrenia-like behaviors. In parallel, neighborhood social fragmentation has been shown to be associated with the onset of psychosis. This study investigates the association between neighborhood social fragmentation and MMN impairment among CHR-P youth and healthy comparisons (HC). Data were collected from the North American Prodrome Longitudinal Study Phase 2. Electroencephalography was recorded during an unattended auditory oddball paradigm with duration-, pitch-, and double-deviant tones. Generalized linear mixed models tested the association between neighborhood social fragmentation and the frontal-central averaged MMN for three deviant types for youth at CHR-P and HC separately. The models adjusted for age, sex, race/ethnicity, parental education, parental history of psychosis, and neighborhood poverty. Participants (mean [SD] age: 18.69 [4.59], 41.9% females, 51.3% White non-Hispanic) included 304 CHR-P and 92 HC. In the CHR-P group, greater neighborhood social fragmentation was associated with impaired duration-deviant MMN (bootstrapped β = 0.18, 95% CI: 0.04 to 0.33, p = .022) but not for pitch-deviant (bootstrapped β = 0.09, 95% CI: -0.05 to 0.22, p = .199) or double-deviant MMN (bootstrapped β = 0.10, 95% CI: -0.09 to 0.17, p = .559). Greater neighborhood social fragmentation was associated with impaired duration-deviant MMN amplitude among high-risk individuals. Further research is needed to explore underlying mechanisms.