2. Academic Validation
  3. Candidate pharmacological treatments for substance use disorder and suicide identified by gene co-expression network-based drug repositioning

Candidate pharmacological treatments for substance use disorder and suicide identified by gene co-expression network-based drug repositioning

  • Am J Med Genet B Neuropsychiatr Genet. 2021 Apr;186(3):193-206. doi: 10.1002/ajmg.b.32830.
Brenda Cabrera-Mendoza 1 2,  José Jaime Martínez-Magaña 1 3,  Nancy Monroy-Jaramillo 4,  Alma Delia Genis-Mendoza 1,  Cristóbal Fresno 5,  Gabriel Rodrigo Fries 6,  Consuelo Walss-Bass 6,  Mauro López Armenta 7,  Fernando García-Dolores 7,  Carlos Enrique Díaz-Otañez 7,  Gonzalo Flores 8,  Rubén Antonio Vázquez-Roque 8,  Humberto Nicolini 1
Affiliations

Affiliations

  • 1 Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico.
  • 2 PECEM, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
  • 3 Multidisciplinary Academic Division of Comalcalco, Juárez Autonomous University of Tabasco, Comalcalco, Tabasco, Mexico.
  • 4 Department of Genetics, National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
  • 5 Department of Technological Development, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico.
  • 6 Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • 7 Institute of Forensic Sciences, Mexico City, Mexico.
  • 8 Neuropsychiatry Laboratory, Institute of Physiology, Meritorious Autonomous University of Puebla, Puebla, Mexico.
PMID: 33403748 DOI: 10.1002/ajmg.b.32830
Abstract

Patients with substance use disorders (SUD) are at high risk to die by suicide. So far, the neurobiology of the suicide-SUD association has not been elucidated. This study aimed to identify potential pharmacological targets among hub genes from brain gene co-expression networks of individuals with SUD in a suicidal and non-suicidal context. Post-mortem samples from the prefrontal cortex of 79 individuals were analyzed. Individuals were classified into the following groups: suicides with SUD (n = 28), suicides without SUD (n = 23), nonsuicides with SUD (n = 9), nonsuicides without SUD (n = 19). Gene expression profiles were evaluated with the Illumina HumanHT-12 v4 array. Co-expression networks were constructed in WGCNA using the differentially expressed genes found in the comparisons: (a) suicides with and without SUD and (b) nonsuicides with and without SUD. Hub genes were selected for drug-gene interaction testing in the DGIdb database. Among drugs interacting with hub genes in suicides we found MAOA inhibitors and dextromethorphan. In the nonsuicide individuals, we found interactions with eglumegad and antipsychotics (olanzapine, clozapine, loxapine). Modafinil was found to interact with genes in both suicides and nonsuicides. These drugs represent possible candidate treatments for patients with SUD with and without suicidal behavior and their study in each context is encouraged.

Keywords

WGCNA; drug-repositioning; gene expression; postmortem; prefrontal cortex; substance-related disorders.

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