A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Florence F. Roussotte, Neda Jahanshad, Derrek P. Hibar, Elizabeth R. Sowell, Omid Kohannim, Marina Barysheva, Narelle K. Hansell, Katie L. Mcmahon, Greig I. de Zubicaray, Grant W. Montgomery, Nicholas G. Martin, Margaret J. Wright, Arthur W. Toga, Clifford R Jr. Jack, Michael W. Weiner, Paul M. Thompson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.

Original languageEnglish (US)
Pages (from-to)1226-1236
Number of pages11
JournalHuman Brain Mapping
Volume35
Issue number4
DOIs
StatePublished - 2014

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delta Opioid Receptor
Brain
Population
Genes
Nervous System Diseases
Neuroimaging
Twin Studies
Queensland
Street Drugs
Opioid Receptors
Individuality
Neurodegenerative Diseases
Substance-Related Disorders
Single Nucleotide Polymorphism
Psychiatry
Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Alleles
Genotype

Keywords

  • Drug addiction
  • Genetics
  • Neurodegeneration
  • Neuroimaging
  • Opiates

ASJC Scopus subject areas

  • Clinical Neurology
  • Anatomy
  • Neurology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Medicine(all)

Cite this

A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes : Replication in elderly and young populations. / Roussotte, Florence F.; Jahanshad, Neda; Hibar, Derrek P.; Sowell, Elizabeth R.; Kohannim, Omid; Barysheva, Marina; Hansell, Narelle K.; Mcmahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Toga, Arthur W.; Jack, Clifford R Jr.; Weiner, Michael W.; Thompson, Paul M.

In: Human Brain Mapping, Vol. 35, No. 4, 2014, p. 1226-1236.

Research output: Contribution to journalArticle

Roussotte, FF, Jahanshad, N, Hibar, DP, Sowell, ER, Kohannim, O, Barysheva, M, Hansell, NK, Mcmahon, KL, de Zubicaray, GI, Montgomery, GW, Martin, NG, Wright, MJ, Toga, AW, Jack, CRJ, Weiner, MW & Thompson, PM 2014, 'A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations', Human Brain Mapping, vol. 35, no. 4, pp. 1226-1236. https://doi.org/10.1002/hbm.22247
Roussotte, Florence F. ; Jahanshad, Neda ; Hibar, Derrek P. ; Sowell, Elizabeth R. ; Kohannim, Omid ; Barysheva, Marina ; Hansell, Narelle K. ; Mcmahon, Katie L. ; de Zubicaray, Greig I. ; Montgomery, Grant W. ; Martin, Nicholas G. ; Wright, Margaret J. ; Toga, Arthur W. ; Jack, Clifford R Jr. ; Weiner, Michael W. ; Thompson, Paul M. / A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes : Replication in elderly and young populations. In: Human Brain Mapping. 2014 ; Vol. 35, No. 4. pp. 1226-1236.
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