# Neurobiology of Aggression Comorbidity in Autism

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $432,500

## Abstract

PROJECT SUMMARY
 Aggression is a frequent comorbidity in autism spectrum disorders (ASD). The problem is one of the
major reasons families seek medical therapy. Understanding the molecular basis and deciphering the neural
circuits that contribute to the development of this aggression comorbidity could inform novel targeted
therapeutics. Increased copies of maternal chromosome 15q11-13 region [interstitial duplication with a
single extra copy and extranumerary isodicentric chromosome 15q (Idic15) with two extra copies] are
frequent and strongly penetrant (Idic15) causes of ASD. We have recently established that extra copies
of Ube3a alone (15q11-13 gene expressed exclusively from maternal allele in neurons) are sufficient to
reproduce ASD-like deficits in mice (Smith et al. 2011). Interestingly, mice with extra copies of Ube3a
also show increased aggression. Taken together, these observations indicate that aberrant expression of
Ube3a underlies multiple ASD-associated behavioral problems. In this project we will dissect Ube3a's
role in controlling the aggression-comorbidity of ASD: 1) Identify specific neuronal cell types where
increased Ube3a gene dosage increase aggression and identify underlying transcriptional and
electrophysiological changes; and 2) Identify synaptic connections that are disrupted by increased Ube3a
gene dosage to increase aggression within those neuronal cell types. The project promotes the agency's
mission to further a deeper understanding of the neuronal cells, circuits, and genes involved in ASD via
genetic models. The novel molecular insights and genetic tools will facilitate development of treatments
for these life-long behavioral disabilities.

## Key facts

- **NIH application ID:** 9929029
- **Project number:** 5R01MH114858-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** MATTHEW P ANDERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,500
- **Award type:** 5
- **Project period:** 2017-09-12 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929029

## Citation

> US National Institutes of Health, RePORTER application 9929029, Neurobiology of Aggression Comorbidity in Autism (5R01MH114858-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9929029. Licensed CC0.

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