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Defining and Engaging a Novel rTMS Target for Nicotine Craving in Psychotic Disorders

Heather Burrell Ward1, Sophia H Blyth1, Simon Vandekar2

  • 1Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN.

Medrxiv : the Preprint Server for Health Sciences
|November 19, 2025
PubMed

Insights

Tobacco use in schizophrenia is linked to altered default mode network (DMN) organization. Engaging the DMN with repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing nicotine craving in psychosis patients.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Addiction Medicine

Background:

  • Tobacco use is a leading cause of preventable mortality in schizophrenia, yet its underlying mechanisms are poorly understood.
  • Previous studies suggest nicotine may normalize default mode network (DMN) disorganization in schizophrenia.
  • The Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) cohort provides a large sample to investigate psychosis spectrum disorders.

Purpose of the Study:

  • To validate the association between DMN organization and tobacco use in a large psychosis-spectrum sample.
  • To evaluate the impact of single and multiple sessions of DMN-targeted repetitive transcranial magnetic stimulation (rTMS) on nicotine craving.

Main Methods:

  • Cross-sectional analysis of the B-SNIP2 cohort (n=596) to assess DMN connectivity in relation to smoking status.
  • A single-session rTMS study (n=10) using intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), or sham, with pre-/post-neuroimaging and craving assessment.
  • An accelerated, multi-session rTMS study (n=12) using DMN-targeted cTBS over 5 sessions, with pre-/post-neuroimaging and craving assessment.

Main Results:

  • In B-SNIP2, current smokers exhibited significantly lower DMN connectivity compared to former and never smokers, a finding consistent within the psychosis subgroup.
  • Single-session iTBS was associated with increased craving, while multi-session DMN-targeted cTBS significantly reduced craving after each session and decreased DMN connectivity.
  • The results suggest a potential mechanism linking nicotine use to DMN alterations in psychosis.

Conclusions:

  • Altered DMN connectivity is associated with tobacco use in individuals with psychosis.
  • DMN-targeted repetitive transcranial magnetic stimulation (rTMS), particularly multi-session cTBS, may serve as a novel therapeutic target for reducing nicotine craving in psychosis.
  • Further research is warranted to explore the therapeutic potential of rTMS for smoking cessation interventions in this population.
Keywords:
default mode networknicotine dependencepsychosisresting-state functional connectivityschizophreniatheta-burst stimulationtranscranial magnetic stimulation

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