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Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework.

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Title:	Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework.
Authors:	Russell NM; Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 2409 University Ave., Austin, TX, 78712, USA., Frier MD; Department of Psychology, Tufts University, Medford, MA, USA., Bortolato M; Department of Cellular and Systems Pharmacology, College of Pharmacy, University of Florida, Gainesville, 1345 Center Dr, 32611, FL, USA. mbortolato@ufl.edu., Mangieri RA; Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 2409 University Ave., Austin, TX, 78712, USA. reginamangieri@utexas.edu.; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX, USA. reginamangieri@utexas.edu.
Source:	Psychopharmacology [Psychopharmacology (Berl)] 2025 Oct 31. Date of Electronic Publication: 2025 Oct 31.
Publication Model:	Ahead of Print
Publication Type:	Journal Article; Review
Language:	English
Journal Info:	Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7608025 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2072 (Electronic) Linking ISSN: 00333158 NLM ISO Abbreviation: Psychopharmacology (Berl) Subsets: MEDLINE
Imprint Name(s):	Original Publication: Berlin, New York, Springer-Verlag.
Abstract:	Rationale: The relationship between alcohol misuse and aggression has long intrigued clinical and preclinical researchers. While acute alcohol use is well known to promote aggression, converging evidence indicates a more complex, bidirectional association. Both behaviors often arise from shared genetic, neurobiological, and environmental vulnerabilities and can mutually increase risk, creating a vicious spiral in which alcohol misuse and aggression reinforce one another over time. Objective: This review synthesizes epidemiological, clinical, and experimental findings to establish an integrated framework linking alcohol misuse and aggression, while introducing a translational perspective connecting human and animal research. Results & Conclusions: The relationship between alcohol misuse and aggression can be conceptualized through two complementary models. In the first, alcohol use facilitates aggression: acute intoxication disrupts executive control and heightens emotional reactivity, while chronic exposure induces neuroadaptations that sensitize individuals to aggression-promoting effects and may elevate aggression during abstinence. In the second, aggression increases vulnerability to alcohol misuse: longitudinal studies reveal that aggressive traits, emotional dysregulation, and externalizing psychopathology frequently precede problematic drinking. These pathways are influenced by shared dysfunctions within prefrontal-limbic circuits involved in emotion regulation and impulse control. Despite progress in modeling alcohol-induced aggression, little research addresses how aggressive phenotypes contribute to alcohol misuse, representing an important translational gap. Overall, this relationship is best understood as a dynamic, bidirectional system rooted in overlapping neurobehavioral mechanisms. By integrating clinical findings with preclinical models, this framework highlights targets for mechanistic investigation and the development of tailored therapeutic strategies. (© 2025. The Author(s).)
Competing Interests:	Declarations. Ethical approval: Not Applicable. Consent to participate: Not applicable. Consent to publish: All authors consent to this manuscript being published. Conflict of interest: On behalf of all authors, the corresponding authors state that there is no conflict of interest.
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Grant Information:	AA030256 United States AA NIAAA NIH HHS; AA030256 United States AA NIAAA NIH HHS; AA016651 United States AA NIAAA NIH HHS; MH104603 United States MH NIMH NIH HHS; MH104603 United States MH NIMH NIH HHS; Billi Terresa Cowden Endowment Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin
Contributed Indexing:	Keywords: Aggression; Alcohol; Animal models; Behavior; Early-Life stress; Neurodevelopment; Neuroimaging
Entry Date(s):	Date Created: 20251031 Latest Revision: 20251031
Update Code:	20251101
DOI:	10.1007/s00213-025-06938-0
PMID:	41171339
Database:	MEDLINE

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