A systematic review of the etiology and neurobiology of intermittent explosive disorder
- PMID: 40023093
- DOI: 10.1016/j.psychres.2025.116410
A systematic review of the etiology and neurobiology of intermittent explosive disorder
Abstract
Intermittent Explosive Disorder (IED) is characterized by repeated inability to control aggressive impulses. Although the etiology and neurobiology of impulsive anger and impulse control disorders have been reviewed, no systematic review on these aspects has been published for IED specifically. We conducted a systematic search in seven electronic databases for publications about IED, screened by two authors, and retained twenty-four studies for the review. Our findings highlight a multifactorial etiology and neurobiology of IED, emphasizing the role of the amygdala and orbitofrontal cortex in emotional regulation and impulse control, and supporting interventions that target serotonergic signaling. Research also shows that childhood trauma and adverse family environment may significantly contribute to the development of IED. Yet, genetic studies focusing on IED were largely lacking, despite many examining the genetics underlying aggression as a general trait or other related disorders. Future research using consistently defined IED as a phenotype is required to better understand the etiology and underlying mechanisms and assist in informing the development of more effective interventions for IED.
Keywords: Aggression; Amygdala; Childhood trauma; Family environment; Hypothalamus; Impulsive aggression; Intermittent explosive disorder; Orbitofrontal cortex; Serotonin; Socioeconomic status.
Copyright © 2025 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest SVF received income, potential income, travel expenses continuing education support and/or research support from Aardvark, Aardwolf, AIMH, Akili, Atentiv, Axsome, Genomind, Ironshore, Johnson & Johnson/Kenvue, Kanjo, KemPharm/Corium, Noven, Otsuka, Sky Therapeutics, Sandoz, Supernus, Tris, and Vallon. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.ADHDEvidence.org and www.ADHDinAdults.com. SVF received research support from Corium Pharmaceuticals, Tris Pharmaceuticals and Supernus Pharmaceutical Company. JS declares financial relationships with the following entities: Amneal Pharmaceuticals LLC, Viatris Inc., Organon & Co. Inc., Medtronic Inc., Bristol-Myers Squibb, and Psychological Skills Press, all of which include equity or stock holdings. Additionally, he serves as a board member for the Organization for Psychoeducational Tutoring, Inc. Joseph Strayhorn declares financial relationships with the following entities: Amneal Pharmaceuticals LLC, Viatris Inc., Organon & Co. Inc., Medtronic Inc., Bristol-Myers Squibb, and Psychological Skills Press, all of which include equity or stock holdings. Additionally, he serves as a board member for the Organization for Psychoeducational Tutoring, Inc. JP, SE, AU, ASS, JE and YZJ have no disclosures to report.
Update of
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A Systematic Review of the Etiology and Neurobiology of Intermittent Explosive Disorder.medRxiv [Preprint]. 2024 Sep 13:2024.09.12.24313573. doi: 10.1101/2024.09.12.24313573. medRxiv. 2024. Update in: Psychiatry Res. 2025 May;347:116410. doi: 10.1016/j.psychres.2025.116410. PMID: 39314952 Free PMC article. Updated. Preprint.
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