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Sex Differences in Brain Disorders Emerging Transcriptomic Evidence: Proceedings of a Workshop (2021) / Chapter Skim
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2 Transcriptomic Evidence for Sex Differences in Stress- and Reward-Related Disorders
Pages 5-14

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From page 5...
... . • Transcriptome analyses in post-mortem brain tissue have dem onstrated highly distinct profiles and gene networks with little overlap between men and women with depression, and these findings have been replicated in mouse models (Issler, Seney)
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From page 6...
... She added that females with substance use disorders demonstrate a higher propensity for stress-induced relapse and a higher incidence of comorbid stress-related psychiatric disorders. Valentino added that cognitive and affective features associated with depression, anxiety, PTSD, and pain disorders -- negative affect, increased arousal, and reward deficit -- are also linked to stress in that they have a common circuitry that interacts with stress circuitry.
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From page 7...
... They have used large-scale transcriptomic studies conducted using unbiased approaches such as microarray or RNA sequencing technologies. For example, in what Seney called a tour-de-force study, Eric Nestler's lab used transcriptomic approaches to analyze a large cohort of well-­ characterized post-mortem brains across six different brain regions involved in mood regulation (Labonté et al., 2017)
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From page 8...
... Her lab went on to show that differentially expressed genes were enriched for synapse structure, function, and organization (decreased expression in men versus increased expression in women) and immune function (increased expression or no change in men versus decreased expression in women)
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From page 9...
... Girgenti and colleagues examined the impact of multiple covariates on differential gene expression and found, to their surprise, that the overwhelming amount of differential variance was caused by sex. In females, substantial gene expression changes were seen in three brain regions, while in males, differential gene expression occurred only in one region, and there was very little overlap between male and female brains in terms of their gene expression profiles.
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From page 10...
... Her research as a postdoctoral fellow in Nestler's lab using an adolescent stress paradigm in mice demonstrated that social isolation drives a big sex difference in behavior: In comparison to group-housed animals where males and females showed an equal preference for cocaine, socially isolated males showed a greater
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From page 11...
... To assess changes in global transcriptional structure and potentially identify targets that regulate sex differences in reward, Walker and colleagues used an updated co-expression analytical technique called multiscale embedded gene coexpression network analysis (MEGENA)
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From page 12...
... Using an inflammatory pain model, Price and colleagues have shown in female mice that a CGRP-sequestering antibody prevented both the development of mechanical hypersensitivity and the transition to a chronic pain state called hyperalgesic priming. In males, the antibody had no such effect, he said.
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From page 13...
... This could explain why antagonists against specific receptors may have limited effectiveness in different population groups, suggested Price. ADDITIONAL FACTORS CONTRIBUTING TO SEX DIFFERENCES IN STRESS- AND REWARD-RELATED DISORDERS While the workshop focused on transcriptomic evidence, genetic regulatory networks are also affected by epigenetic mechanisms triggered by environmental influences, including stress, according to Farah Lubin, associate professor of neurobiology at The University of Alabama at Birmingham.
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Key Terms

  • chronic pain
  • brain disorders
  • socially isolated
  • little overlap
  • brain regions

  • transcriptomic differences
  • prefrontal cortex
  • robust sex
  • transcriptomic studies
  • neuropathic pain

  • expression changes
  • increased expression
  • decreased expression
  • technique called
  • social isolation

  • depressed women
  • endothelial cells
  • differentially expressed
  • identify gene
  • differential gene

  • gene networks
  • adolescent stress
  • stress disorder
  • isolated males
  • marianne seney

  • isolated females
  • dorsolateral prefrontal
  • transcriptional response
  • mood regulation
  • frontal cortex


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