Study Identifies Comorbidities of Intermittent Explosive Disorder

A new study identified comorbidities of intermittent explosive disorder: substance use disorder, adult personality and behavior disorders, neurodegenerative diseases, epilepsy, movement disorders, cerebral palsy, sleep disorders, obesity, hyperlipidemia, hypertension, and gastroesophageal reflux disease. Some of these comorbidities had a greater risk in this patient population than others, such as disorders of adult personality and behavior which had a hazard risk of 76.6.

“Although IED is a quintessential externalizing disorder, it was strongly comorbid with both anxiety and mood disorders,” wrote investigators, led by Yanli Zhang-James, MD, PhD, from Norton College of Medicine, SUNY Upstate Medical University in Syracuse.

Intermittent explosive disorder, characterized by impulsive aggression and emotional dysregulation, is diagnosed in individuals who do not meet the criteria for bipolar disorder, borderline personality disorder, intoxication, or withdrawal from substances. It can occur with ADHD or oppositional defiant disorder but remains challenging to diagnose. According to the Mayo Clinic, intermittent explosive disorder increases the risk for problems with relationships, work or school, mood, alcohol and drug abuse, physical health, and self-harm.2

Investigators emphasized that while aggression is common across bipolar disorder or borderline personality disorder, it does not equate to intermittent explosive disorder for those with aggressive tendencies. Since research on its comorbidities is limited, investigators sought to characterize the presence of the comorbidities of intermittent explosive disorder, particularly its association with psychiatric, neurological, and somatic disorders.

The team included patients from the TriNetX Research Network, matching those with and without explosive disorders. In each group, 70% were male (n = 21,313), with a mean age of 26 years at the first visit. In total, 0.03% of patients in the network had intermittent explosive disorder, representing 33,410 individuals.

“The low diagnostic rates and high psychiatric comorbidity together may likely reflect the well-known challenges in diagnosing IED, where individuals may receive alternative diagnoses first or no diagnosis at all, depending on the clinician’s awareness and familiarity with IED, as well as their preference for diagnosing and treating aggression within the context of other comorbidities,” investigators wrote.

The team observed patients with intermittent explosive disorder had extensive comorbidities with psychiatric, neurological, and somatic conditions. Intermittent explosive disorder was associated with the greatest risk of mental, behavioral, and neurodevelopmental disorders (hazard ratio [HR], 3.4; 95% confidence interval [CI], 3.3 – 3.5), followed by nervous system diseases (HR, 1.9; 95% CI, 1.8 – 2.0).

95.7% of patients with intermittent explosive disorder (n = 29,054) had another psychiatric diagnosis, whereas only 28.6% of individuals without intermittent explosive disorder had ≥ 1 psychiatric disorder. Psychiatric conditions significantly associated with intermittent explosive disorder included disordes of adult personality and behavior (HR, 76.6; 95% CI, 65.4 – 89.6) and substance use disorder (HR, 2.1; 95% CI, 2.0 – 2.2).

Patients with intermittent explosive disorder, compared to patients without, had greater prevalence in neurodegenerative diseases (4.4% vs 0.5%; HR, 5.0; 95% CI, 4.1 – 6.1) and epilepsy (14.1% vs 1.7%; HR, 4.9; 95% CI, 4.2 – 5.6). Intermittent explosive disorder was also associated with extrapyramidal and movement disorders (HR, 3.1; 95% CI, 2.8 – 3.5), cerebral palsy and other paralytic syndromes (HR, 2.6; 95% CI, 2.2 – 3.0), and sleep disorders (HR, 2.2; 95% CI, 2.1 – 2.3). The study also showed more patients with intermittent explosive disorder than without had migraine (9.5% vs 3.7%).

A greater proportion of patients with intermittent explosive disorder had alcohol-related disorders (15.1% vs 3.4%), cannabis-related disorders (15.3% vs 2.0%). Intermittent explosive disorder was also associated with falls, burns, poisonings, injuries, obesity (HR, 1.6; 95% CI, 1.5 – 1.7), hyperlipidemia (HR, 1.5; 95% CI, 1.4 – 1.5), hypertension (HR, 1.6; 95% CI, 1.5 – 1.7, and gastroesophageal reflux disease (HR, 1.7; 95% CI, 1.7 – 1.9).

The study also showed disorders that are significantly associated in both patients with and without intermittent explosive disorder, including developmental disorders (44.5% vs 5.4%), anxiety (59% vs 12.2%), depression (60.3% vs 9.3%), ADHD (37.7% vs 4.9%), and sleep disorders (27.7% vs 7.1%). Overall, patients with intermittent explosive disorder have a significantly increased overall disease burden (P < .001).

“Our findings shed unique light on how IED is diagnosed in clinical practice, distinct from research settings,” investigators wrote. “Highlighting aggression as a separate diagnosis may focus more attention on aggressive behavior and facilitate the development of targeted treatments. Otherwise, aggressive behavior remains somewhat hidden as a feature within other disorders.”

References

1. Zhang-James Y, Paliakkara J, Schaeffer J, Strayhorn J, Faraone SV. Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder. JAMA Psychiatry. 2025 Jan 22. doi: 10.1001/jamapsychiatry.2024.4465. Epub ahead of print. PMID: 39841469.
2. Intermittent Explosive Disorder. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/intermittent-explosive-disorder/symptoms-causes/syc-20373921. Accessed January 22, 2025.