# Disentangling the biological links between violence and alcohol use

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $547,986

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol misuse is often associated with pathological aggression, a recurrent pattern of disruptive and violent
behavior. Despite the significant socioeconomic burden imposed by the repercussions of this comorbidity, avail-
able treatments are limited and inadequate. A critical problem in treating the association of alcohol misuse and
pathological aggression lies in the complex links between these two entities: on the one hand, alcohol worsens
violence propensity in predisposed individuals; on the other hand, anger and aggression increase the risk of
alcohol use. Disentangling the links between these conditions is critical to developing better therapies.
To study these neurobiological mechanisms, we focused on the best-characterized gene × environment (G×E)
interaction underlying pathological aggression and alcohol use, occurring between low-activity alleles of the
MAOA gene (encoding the enzyme monoamine oxidase A) and child maltreatment. We recently developed the
first animal model of this G×E interaction by subjecting a line of mice with an MAOA hypomorphic mutation to
early-life stress during the first week of life.
The studies proposed in this application will test the hypothesis that the interaction of low-activity MAOA variants
and child maltreatment leads to alterations of the prefrontal cortex and nucleus accumbens, which predispose
to a vicious cycle of increased alcohol use and aggression. The three Aims of this proposal will focus on 1) the
common neurodevelopmental mechanisms of these two problems; 2) the adverse effects of alcohol drinking on
aggression; and 3) the impact of anger and social reactivity on the propensity to drink alcohol. Taken together,
this research will help elucidate the mechanisms of the comorbidity of alcohol misuse and pathological aggres-
sion and identify new potential targets for the prevention and treatment of alcohol-associated violence.

## Key facts

- **NIH application ID:** 10852919
- **Project number:** 5R01AA030256-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Marco Bortolato
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $547,986
- **Award type:** 5
- **Project period:** 2023-06-01 → 2024-12-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852919

## Citation

> US National Institutes of Health, RePORTER application 10852919, Disentangling the biological links between violence and alcohol use (5R01AA030256-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852919. Licensed CC0.

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