Symptom networks and working memory in schizophrenia: a multi-methodological cross-sectional study from phenotype to...

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Working memory (WM) deficits are a hallmark of schizophrenia, but their precise relationship with specific symptoms remains unclear.
• Understanding these links is crucial for developing targeted interventions for schizophrenia.
• This study investigates the neural and molecular underpinnings of WM impairment in schizophrenia.

Purpose of the Study:

• To explore the connectome patterns linking working memory deficits and psychiatric symptoms in schizophrenia.
• To identify core symptoms influenced by working memory performance using symptom network analysis (SNA).
• To investigate the genetic and molecular basis of the identified neural networks.

Main Methods:

• Utilized symptom network analysis (SNA) to identify key symptoms associated with working memory performance.
• Employed Connectome-Based Predictive Modeling (CPM) to link functional brain connectome patterns to symptom severity.
• Performed gene annotation enrichment analysis to explore molecular pathways involved in the predictive network.

Main Results:

• Symptom network analysis identified disorganized attention (PANSS G11) as the most prominent symptom linked to working memory deficits.
• Connectome-Based Predictive Modeling demonstrated that the working memory-related functional connectome significantly predicted disorganized attention severity in two independent patient samples.
• The predictive network primarily involved frontoparietal and frontolimbic brain regions, with gene enrichment analysis pointing to a role for cytoplasmic protein binding.

Conclusions:

• Impaired working memory in schizophrenia is associated with altered frontoparietal and frontolimbic connectivity.
• This connectivity preferentially impacts the severity of disorganized attention.
• Cytoplasmic protein binding may represent a key molecular mechanism underlying working memory deficits and attentional disorganization in schizophrenia, meriting further research.