Importance: Intermittent Explosive Disorder (IED) is an understudied psychiatric condition that presents with repeated episodes of impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities will allow for enhanced screening, diagnosis, and treatment of patients. Objective: To investigate prevalence and associations of IED with psychiatric, neurological, and somatic disorders using real-world data Design: Matched cohorts of patients with or without IED diagnosis were identified using data from the TriNetX Research Network (until January 31, 2024). Cox proportional hazard models were used to estimate and compare the probabilities of acquiring other diagnoses using patients' available medical records. Setting: Analysis of electronic medical records from two patient populations. Participants: 30,357 individuals with IED and equal number of demographically matched individ-uals without IED from the TriNetX Research. Exposure: IED diagnosis identified through the associated ICD codes. Main Outcomes and Measures: The main outcomes were ICD-10-CM diagnostic categories and root codes for disorders and health conditions in both cohorts. Main measures are total numbers and proportions of patients who had the diagnostic codes, as well as adjusted hazard ratios for IED diagnosis. Results: Although only 0.03% of the total patient population had an IED diagnosis, we found ex-tensive and widespread comorbidities with psychiatric, neurological and somatic conditions. A significant 95.7% of the individuals with IED had another psychiatric diagnosis. All psychiatric sub-categories and 95% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2 to 77. Among neurological conditions, neurodegenerative diseases and epi-lepsy had the highest HRs, followed by extrapyramidal and movement disorders, cerebral palsy and other paralytic syndromes, and sleep disorders. Notable associations with IED also includes conditions such as obesity, hyperlipidemia, hypertension, and GERD. Conclusion and Relevance: Our findings illuminate the extensive comorbid relationships be-tween IED and psychiatric, neurological, and somatic disorders. This underscores the necessity for an integrated diagnostic and treatment approach that addresses both the psychological and physical health aspects of IED. Additionally, our work highlights the need for more accurate and inclusive diagnosis of IED in patients with mental disorders.

Stephen Faraone in the past 36 months received income, potential income, travel expenses continuing education support and/or research support from Arbor, Aardvark, Aardwolf, AIMH, Akili, Atentiv, Axsome, Genomind, Ironshore, Johnson & Johnson/Kenvue, Kanjo, KemPharm/Corium, Medice, Noven, Ondosis, Otsuka, Rhodes, Sky Therapeutics, Sandoz, Supernus, Takeda, 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. Dr. Faraone's research is supported by the Upstate Foundation, the European Union's Horizon 2020 research and innovation programme under grant agreement 965381; NIH/NIMH grants U01AR076092-01A1, 1R21MH1264940, U01AR076092, R01MH116037, 1R01NS128535, R01MH131685, 1R01MH130899, U01MH135970, and Supernus Pharmaceuticals. His continuing medical education programs are supported by The Upstate Foundation, Corium Pharmaceuticals, Oregon Health & Science University, Tris Pharmaceuticals and Supernus Pharmaceuticals. All other authors have no disclosures to report.

The study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Because only de-identified medical records were used, the study was determined to be non-human study by the SUNY Upstate Medical University Institutional Review Board.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present work are contained in the manuscript and available online at MedRxiv. Patient medical records were only available directly from TriNetX.