Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder

Robert Hitzemann, Susan E. Bergeson, Ari E. Berman, Jason A. Bubier, Elissa J. Chesler, Deborah A. Finn, Matthew Hein, Paula Hoffman, Andrew Holmes, Brent R. Kisby, Denesa Lockwood, Kerrie H. Lodowski, Michelle McManus, Julie A. Owen, Angela R. Ozburn, Praneetha Panthagani, Igor Ponomarev, Laura Saba, Boris Tabakoff, Aashlesha WalchaleRobert W. Williams, Tamara J. Phillips

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


There is compelling evidence that sex and gender have crucial roles in excessive alcohol (ethanol) consumption. Here, we review some of the data from the perspective of brain transcriptional differences between males and females, focusing on rodent animal models. A key emerging transcriptional feature is the role of neuroimmune processes. Microglia are the resident neuroimmune cells in the brain and exhibit substantial functional differences between males and females. Selective breeding for binge ethanol consumption and the impacts of chronic ethanol consumption and withdrawal from chronic ethanol exposure all demonstrate sex-dependent neuroimmune signatures. A focus is on resolving sex-dependent differences in transcriptional responses to ethanol at the neurocircuitry level. Sex-dependent transcriptional differences are found in the extended amygdala and the nucleus accumbens. Telescoping of ethanol consumption is found in some, but not all, studies to be more prevalent in females. Recent transcriptional studies suggest that some sex differences may be due to female-dependent remodeling of the primary cilium. An interesting theme appears to be developing: at least from the animal model perspective, even when males and females are phenotypically similar, they differ significantly at the level of the transcriptome.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalBiological Psychiatry
Issue number1
StatePublished - Jan 1 2022


  • Binge
  • Ethanol
  • Functional genomics
  • Neural circuitry
  • Neuroimmune function
  • Therapeutics

ASJC Scopus subject areas

  • Biological Psychiatry


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