Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Rachel C Rice; Daniela V Gil; Annalisa M Baratta; Remy R Frawley; Shirley Y Hill; Sean P Farris; Gregg E Homanics

doi:10.1016/j.ynstr.2023.100603

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Neurobiol Stress. 2023 Dec 25:29:100603. doi: 10.1016/j.ynstr.2023.100603. eCollection 2024 Mar.

Authors

Rachel C Rice¹, Daniela V Gil¹, Annalisa M Baratta¹, Remy R Frawley², Shirley Y Hill^{3

4

5}, Sean P Farris^{1

2

6}, Gregg E Homanics^{1

2

7}

Affiliations

¹ Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA.
² Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Chronic stress and alcohol (ethanol) use are highly interrelated and can change an individual's behavior through molecular adaptations that do not change the DNA sequence, but instead change gene expression. A recent wealth of research has found that these nongenomic changes can be transmitted across generations, which could partially account for the "missing heritability" observed in genome-wide association studies of alcohol use disorder and other stress-related neuropsychiatric disorders. In this review, we summarize the molecular and behavioral outcomes of nongenomic inheritance of chronic stress and ethanol exposure and the germline mechanisms that could give rise to this heritability. In doing so, we outline the need for further research to: (1) Investigate individual germline mechanisms of paternal, maternal, and biparental nongenomic chronic stress- and ethanol-related inheritance; (2) Synthesize and dissect cross-generational chronic stress and ethanol exposure; (3) Determine cross-generational molecular outcomes of preconception ethanol exposure that contribute to alcohol-related disease risk, using cancer as an example. A detailed understanding of the cross-generational nongenomic effects of stress and/or ethanol will yield novel insight into the impact of ancestral perturbations on disease risk across generations and uncover actionable targets to improve human health.

Keywords: Alcohol; Epigenetics; Inheritance; Intergenerational; Stress; Transgenerational.

Abstract

Grants and funding