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Candidate pharmacological treatments for substance use disorder and suicide identified by gene co‐expression network‐based drug repositioning
Author(s) -
CabreraMendoza Brenda,
MartínezMagaña José Jaime,
MonroyJaramillo Nancy,
GenisMendoza Alma Delia,
Fresno Cristóbal,
Fries Gabriel Rodrigo,
WalssBass Consuelo,
López Armenta Mauro,
GarcíaDolores Fernando,
DíazOtañez Carlos Enrique,
Flores Gonzalo,
VázquezRoque Rubén Antonio,
Nicolini Humberto
Publication year - 2021
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32830
Subject(s) - context (archaeology) , psychiatry , drug , candidate gene , olanzapine , medicine , substance abuse , gene , dextromethorphan , pharmacology , schizophrenia (object oriented programming) , psychology , bioinformatics , biology , genetics , paleontology
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.