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Parietal Default Mode Network Connectivity is Associated with Tobacco Use in Psychosis
Medrxiv : the Preprint Server for Health Sciences
|March 23, 2026
Summary
Psychosis alters the link between default mode network (DMN) connectivity and tobacco use. Targeting DMN connectivity may offer a specific treatment for nicotine dependence in psychosis patients.
Area of Science:
- Neuroscience
- Psychiatry
- Addiction Research
Background:
- Abnormal default mode network (DMN) connectivity is linked to both tobacco use and psychotic disorders.
- The impact of psychosis on the DMN connectivity-tobacco use relationship is not well understood.
- The left lateral parietal DMN node (LLP_DMN) is a potential target for modulating DMN connectivity and nicotine craving in psychosis.
Purpose of the Study:
- To investigate the relationship between DMN connectivity, psychotic illness, and tobacco use.
- To determine if psychosis diagnosis modifies the association between DMN connectivity and tobacco use.
- To identify specific DMN nodes and networks involved in this interaction.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) was used in 336 participants (161 with psychosis, 175 controls).
- Connectivity within and between the DMN and salience network (SN) was analyzed, focusing on the LLP_DMN.
- Logistic and LASSO regression models examined diagnosis-by-connectivity interactions on lifetime tobacco use, with exploratory brainwide analyses for daily cigarette use.
Main Results:
- A significant diagnosis-by-DMN connectivity interaction was found for lifetime tobacco use, with higher DMN connectivity associated with increased odds in the psychosis group.
- Key predictors of lifetime tobacco use included age, diagnosis, LLP_DMN connectivity to SN and DMN nodes, and their interactions.
- Brainwide analysis revealed that higher LLP_DMN connectivity correlated with increased daily cigarette use in bilateral somatomotor clusters.
Conclusions:
- Psychosis diagnosis significantly modifies the relationship between DMN connectivity and tobacco use.
- Modulating DMN connectivity presents a potential psychosis-specific therapeutic target for tobacco dependence.
- Findings highlight the role of specific DMN nodes, like LLP_DMN, in the interplay between psychosis and nicotine addiction.
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