ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment

Francina Fonseca, Mònica Gratacòs, Geòrgia Escaramís, Rafael De Cid, Rocío Martín-Santos, Magi Farré, Xavier Estivill, Marta Torrens

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Abstract

Methadone maintenance treatment is the most widely-used therapy in opioid dependence, but some patients relapse or drop out from treatment. We genotyped a genetic variant in the succinic semialdehyde dehydrogenase enzyme gene, ALDH5A1, and found that subjects carrying the T variant allele have a higher risk to be nonresponders to methadone treatment (OR=3.16; 95% CI [1.48-6.73], P=0.0024). This could be due to a reduction in the ALDH5A1 enzyme activity, that would increase endogenous gamma-hydroxbutyric acid (GHB) and gamma-aminobutyric acid (GABA) levels and therefore, inducing symptoms such as sedation and impaired pschomotor performance. These neuropsychological effects related with the reduction in enzyme activity could be responsible for a higher propensity to relapse in these genetically predisposed patients. © 2013 Elsevier B.V. and ECNP.
Original languageEnglish
Pages (from-to)420-424
JournalEuropean Neuropsychopharmacology
Volume24
Issue number3
DOIs
Publication statusPublished - 1 Mar 2014

Keywords

  • ALDH5A1 gene
  • Gamma-aminobutyric acid
  • Gamma-hydroxibutyric acid (GHB)
  • Methadone maintenance treatment (MMT)
  • Opioid dependence
  • Pharmacogenetics

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    Fonseca, F., Gratacòs, M., Escaramís, G., De Cid, R., Martín-Santos, R., Farré, M., Estivill, X., & Torrens, M. (2014). ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment. European Neuropsychopharmacology, 24(3), 420-424. https://doi.org/10.1016/j.euroneuro.2013.10.003