Brain functional connectivity associated with cognitive deficits in younger patients at first episode of schizophrenia

Background

Cognitive deficits are a core feature of schizophrenia and are influenced by the age at onset of psychosis. Both preclinical and early-onset schizophrenia patients exhibit abnormalities in the frontal cortex, parahippocampus, precuneus, and hippocampus—regions that are closely associated with cognitive deficits. This study examines whether cognitive-related functional connectivity (FC) within these regions differs in first-episode schizophrenia (FES) patients with varying ages of onset.

Methods

FES patients (ages 18–45, n = 24) and matched healthy controls (HC, n = 29) were divided into younger and older subgroups based on the median age of 25 years: FES_young, FES_older, HC_young, and HC_older. All participants completed the MATRICS Consensus Cognitive Battery (MCCB) and underwent resting-state functional magnetic resonance imaging. FC within regions of interest (ROIs) was analyzed using the CONN toolbox.

Results

Significant cognitive differences were observed between the four groups (H = 13.447, p = 0.004, Rank ε² = 0.259). The most prominent differences were found between the FES_young and HC_young groups (Holm-adjusted p = 0.012). Cognitive deficits in FES patients were significantly associated with reduced FC between the right precuneus (A31_R) and right parahippocampal gyrus (TI_R) (rho = 0.549, p = 0.010, Fisher's z = 0.616). FES_young showed significantly lower FC between A31_R and TI_R compared to HC_young (Holm-adjusted p = 0.001).

Conclusion

Earlier onset schizophrenia is associated with more severe cognitive deficits and specific impairments in brain functional connectivity. These findings highlight the importance of considering age of onset when assessing cognitive and neural dysfunction in schizophrenia.