Cited by 111Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesAlcohol Consumption and Health Effects

Transcriptome organization for chronic alcohol abuse in human brain

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Farris, S P, Arasappan, D, Hunicke-Smith, S, Harris, R A, Mayfield, R D·2015·Molecular Psychiatry

Abstract

Alcohol dependence is a heterogeneous psychiatric disorder characterized by high genetic heritability and neuroadaptations occurring from repeated drug exposure. Through an integrated systems approach we observed consistent differences in transcriptome organization within postmortem human brain tissue associated with the lifetime consumption of alcohol. Molecular networks, determined using high-throughput RNA sequencing, for drinking behavior were dominated by neurophysiological targets and signaling mechanisms of alcohol. The systematic structure of gene sets demonstrates a novel alliance of multiple ion channels, and related processes, underlying lifetime alcohol consumption. Coordinate expression of these transcripts was enriched for genome-wide association signals in alcohol dependence and a meta-analysis of alcohol self-administration in mice. Further dissection of genes within alcohol consumption networks revealed the potential interaction of alternatively spliced transcripts. For example, expression of a human-specific isoform of the voltage-gated sodium channel subunit SCN4B was significantly correlated to lifetime alcohol consumption. Overall, our work demonstrates novel convergent evidence for biological networks related to excessive alcohol consumption, which may prove fundamentally important in the development of pharmacotherapies for alcohol dependence.

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Authors
Farris, S. P., Arasappan, D., Hunicke-Smith, S., Harris, R. A., & Mayfield, R. D.
Affiliations
The University of Texas at Austin (US)
Corresponding author
Mayfield, R D
Venue
Molecular Psychiatry
Published
2014-12-02
Volume
20
Issue
11
Pages
1438-1447
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2052338190
Cited by
111
References
76
Citations by year
2026: 6 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 6
FWCI
4.57
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Texas at Austin
  • University of Sydney
  • National Health and Medical Research Council
  • National Medical Research Council
  • National Institute on Alcohol Abuse and Alcoholism (AA013517, AA020926, P01AA020683, U01AA013517, AA019382, RC2AA019382, R24AA012725, U24AA013517, AA007471, AA012404, R28AA012725, R01AA012404, T32AA007471, U01AA020926)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
chronic alcohol abuse, alcoholism, postmortem brain, gene co-expression network, ion channels, SCN4B, voltage-gated sodium channels, alternative splicing, alcohol self-administration, neural adaptation, alcohol consumption
MeSH terms
Alcohol Drinking, Alcoholism, Animals, Brain, Chronic Disease, Humans, Postmortem Changes, Computational Biology, Gene Expression Profiling, Mice, Gene Regulatory Networks, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Transcriptome, Voltage-Gated Sodium Channel beta-4 Subunit

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