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Dynamic alterations in gene co-expression networks and gene-transcript associations characterize co-morbidities in cocaine use disorder.
Nwaneshiudu, Chinwe; Girdhar, Kiran; Kleopoulos, Steven P; Fullard, John F; Butelman, Eduardo R; Parvaz, Muhammad A; Goldstein, Rita Z; Alia-Klein, Nelly; Roussos, Panos.
Affiliation
  • Nwaneshiudu C; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Girdhar K; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kleopoulos SP; Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fullard JF; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Butelman ER; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Parvaz MA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Goldstein RZ; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Alia-Klein N; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Roussos P; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
bioRxiv ; 2024 Jul 11.
Article de En | MEDLINE | ID: mdl-39026764
ABSTRACT
Background- Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. Methods- We conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. Results- Genes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. Conclusion- We demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: BioRxiv Année: 2024 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: BioRxiv Année: 2024 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: États-Unis d'Amérique