Functional disconnection between subsystems of the default mode network in schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Brain Imaging

Background:

• Dysfunctional default mode network (DMN) connectivity is observed in schizophrenia.
• The stability of DMN deficits across schizophrenia stages remains unclear.

Purpose of the Study:

• To investigate the functional connectivity of DMN subsystems in first-episode schizophrenia (FES) and recurrent schizophrenia (RES) patients.
• To determine if DMN connectivity deficits are stable across different stages of schizophrenia.
• To explore the relationship between DMN connectivity, symptoms, and illness duration.

Main Methods:

• Resting-state functional connectivity analysis was performed on 125 FES/RES patients and 82 controls, with validation in a second cohort.
• Connectivity within and between DMN subsystems (core, dMPFC, MTL) was examined.
• Correlations between connectivity, clinical symptoms, and illness duration were analyzed.

Main Results:

• Schizophrenia patients showed reduced connectivity between core-MTL and within MTL subsystems, consistent across FES and RES groups and validated in a second sample.
• Connectivity between dMPFC-MTL subsystems was also reduced in schizophrenia patients.
• Reduced core subsystem connectivity correlated negatively with clinical symptoms, but no correlation with illness duration was found.

Conclusions:

• Default mode network (DMN) subsystem connectivity deficits are present in schizophrenia and appear early, suggesting a trait-like nature.
• These stable DMN alterations, especially medial temporal lobe (MTL) dysfunction, may be crucial for schizophrenia pathophysiology and early diagnosis.