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Updated: Nov 22, 2025

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
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Published on: December 11, 2016

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Candidate pharmacological treatments for substance use disorder and suicide identified by gene co-expression

Brenda Cabrera-Mendoza1,2, José Jaime Martínez-Magaña1,3, Nancy Monroy-Jaramillo4

  • 1Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
|January 6, 2021
PubMed

Insights

This study explored the brain

Area of Science:

  • Neurobiology
  • Genetics
  • Psychiatry

Background:

  • Patients with substance use disorders (SUD) face a heightened risk of suicide.
  • The underlying neurobiology connecting SUD and suicidal behavior remains largely unknown.
  • Identifying specific biological targets is crucial for developing effective treatments.

Purpose of the Study:

  • To identify potential pharmacological targets by analyzing hub genes in brain gene co-expression networks.
  • To investigate these targets in individuals with SUD, considering both suicidal and non-suicidal contexts.
  • To explore the neurobiological underpinnings of the association between SUD and suicide.

Main Methods:

  • Analysis of post-mortem prefrontal cortex samples from 79 individuals categorized by SUD and suicide status.
  • Gene expression profiling using Illumina HumanHT-12 v4 arrays.
  • Construction of co-expression networks using Weighted Gene Co-expression Network Analysis (WGCNA) and identification of differentially expressed genes.
  • Drug-gene interaction analysis using the Drug-Gene Interaction database (DGIdb).

Main Results:

  • Hub genes in suicides with SUD showed interactions with MAOA inhibitors and dextromethorphan.
  • Hub genes in non-suicide individuals with SUD interacted with eglumegad and antipsychotics (e.g., olanzapine, clozapine).
  • Modafinil interacted with hub genes in both suicidal and non-suicidal individuals with SUD.

Conclusions:

  • MAOA inhibitors, dextromethorphan, eglumegad, and specific antipsychotics are potential therapeutic candidates for SUD patients.
  • Modafinil may hold therapeutic potential across different SUD patient groups.
  • Further research into these drug-gene interactions is encouraged to develop targeted treatments for SUD and suicidal behavior.
Keywords:
WGCNAdrug-repositioninggene expressionpostmortemprefrontal cortexsubstance-related disorders

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