Personality Disorder Symptoms in Intermittent Explosive Disorder: A Latent Class Analysis.

Intermittent explosive disorder (IED) is characterized by recurrent reactive aggression. IED is associated with significant personality pathology that is suggestive of higher levels of general personality disorder (PD). However, little is known about how personality factors impact the severity and presentation of IED. The present study employed a latent class analysis to assess for distinct PD symptom classes within IED and to evaluate whether these classes differed in terms of severity and behavioral presentation. Statistical and clinical indicators revealed a four-class model, with latent classes distinguished primarily on general levels of PD symptoms (low, moderate, high). However, the two moderate PD symptom classes were distinguished from other classes on avoidant PD. In addition, classes differed in terms of severity and presentation, suggesting important implications for both general PD and avoidant PD comorbidity within IED. Results provide further insight into the heterogeneity within IED and suggest a more nuanced approach in treating this serious condition.

Posterior Hypothalamic Region Deep Brain Stimulation for the Treatment of Aggression Disorders in Patients with Intellectual Disability: A Systematic Review.

INTRODUCTION: Aggressive disorders, in patients with intellectual disability, are satisfactorily managed with an educational, psychological, and pharmacological approach. Posterior hypothalamic region deep brain stimulation emerged in the last two decades as a promising treatment for patients with severe aggressive disorders. However, limited experiences are reported in the literature. METHODS: A systematic review was performed following PRISMA guidelines and recommendations by querying PubMed and Embase on August 24th, 2022, with the ensuing string parameters: ([deep brain stimulation] OR [DBS]) AND ([aggressiv*] OR disruptive). Cochrane Library, DynaMed, and ClinicalTrials.gov were consulted using the combination of keywords "deep brain stimulation" and "aggressive" or "aggression". The clinical outcome at the last follow-up and the rate of complications were considered primary and secondary outcomes of interest. RESULTS: The initial search identified 1,080 records, but only 10 studies met the inclusion criteria and were considered. The analysis of clinical outcome and complications was therefore performed on a total of 60 patients. Quality of all selected studies was classified as high, but one. Mean Overt Aggression Scale (OAS) improvement was 68%, while Inventory for Client Agency Planning (ICAP) improvement ranged between 38.3% and 80%. Complications occurred in 4 patients (6.7%). CONCLUSION: Posterior hypothalamic region deep brain stimulation may be considered a valuable option for patients with severe aggression disorders and ID. This review can represent a mainstay for those who will be engaged in the surgical treatment of these patients.

Mental health professionals' use of the ICD-11 classification of impulse control disorders and behavioral addictions: An international field study.

Background and aims: The ICD-11 chapter on mental, behavioral and neurodevelopmental disorders contains new controversial diagnoses including compulsive sexual behavior disorder (CSBD), intermittent explosive disorder (IED) and gaming disorder. Using a vignette-based methodology, this field study examined the ability of mental health professionals (MHPs) to apply the new ICD-11 diagnostic requirements for impulse control disorders, which include CSBD and IED, and disorders due to addictive behaviors, which include gaming disorder, compared to the previous ICD-10 guidelines. Methods: Across eleven comparisons, members of the WHO's Global Clinical Practice Network (N = 1,090) evaluated standardized case descriptions that were designed to test key differences between the diagnostic guidelines of ICD-11 and ICD-10. Results: The ICD-11 outperformed the ICD-10 in the accuracy of diagnosing impulse control disorders and behavioral addictions in most comparisons, while the ICD-10 was not superior in any. The superiority of the ICD-11 was particularly clear where new diagnoses had been added to the classification system or major revisions had been made. However, the ICD-11 outperformed the ICD-10 only in a minority of comparisons in which mental health professionals were asked to evaluate cases with non-pathological high involvement in rewarding behaviors. Discussion and Conclusions: Overall, the present study indicates that the ICD-11 diagnostic requirements represent an improvement over the ICD-10 guidelines. However, additional efforts, such as training programs for MHPs and possible refinements of diagnostic guidance, are needed to avoid over-diagnosis of people who are highly engaged in a repetitive and rewarding behavior but below the threshold for a disorder.

Laboratory assessment of aggression: The Taylor Aggression Paradigm in adults with and without a disorder of impulsive aggression.

INTRODUCTION: The modified Taylor Aggression Paradigm (TAP) has been used to study impulsive aggression in experimental designs and has been relatively successful in addressing critiques of aggression paradigms; however, little has been done to examine the potential of using the TAP as a direct measure of aggression. This study aimed to explore the psychometric properties of the TAP behavioral indexes as measures of aggression. METHODS: A community sample of 962 adults were divided into three groups based on diagnostic assessments: Intermittent Explosive Disorder; Non-Aggressive Psychiatric Disorder; or healthy controls. Participants then completed the TAP and self-report measures to assess construct validity. A subset of 47 participants completed a second TAP within one year to assess reliability. TAP indexes were based on number of "extreme" shocks selected (high shock index), average shock levels selected (mean shock index), and shocks levels selected without provocation (unprovoked aggression). RESULTS: Overall, TAP indexes were consistent and reliable. IED participants had the highest high shock and mean shock indexes of all groups (X2 = 49.93, p < 0.001). High shock index was related to trait aggression (ß = 0.184, p < 0.001) after including covariates; mean shock index had a trending association with trait anger (ß = 0.102, p = 0.059). CONCLUSION: TAP behavioral indexes demonstrated promising psychometrics as a measure of aggression. High shock index appears to be more strongly associated with aggressive behavior; mean shock index may better measure general hostile responding. Future research might include comparisons specifically with impulse control disorders.

Serotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine.

RATIONALE: Characterizing the neuroanatomical basis of serotonergic abnormalities in severe, chronic, impulsive aggression will allow for rational treatment selection, development of novel therapeutics, and biomarkers to identify at-risk individuals. OBJECTIVES: The aim of this study is to identify associations between regional serotonin transporter (5-HTT) availability and trait and state aggression, as well as response to the anti-aggressive effects of fluoxetine. METHODS: We examined 5-HTT availability using positron emission tomography (PET) imaging with [11C]DASB in personality disordered patients with current physical intermittent explosive disorder (IED; n = 18), and healthy comparison participants (HC; n = 11), in the anterior cingulate cortex (ACC), amygdala (AMY), ventral striatum (VST), and midbrain (MID). After PET imaging, IED patients were treated with fluoxetine 20 mg daily (n = 9) or placebo (n = 6) for 12 weeks. Trait and state aggression, trait callousness, and childhood trauma were assessed. RESULTS: In IED patients, trait aggression was positively associated with [11C]DASB binding in the ACC and VST; covarying for trait callousness and childhood trauma enhanced these correlations. Baseline state aggression was positively correlated with ACC [11C]DASB in IED patients. Greater baseline VST [11C]DASB binding predicted greater decreases in state aggression with fluoxetine treatment. CONCLUSIONS: Consistent with prior reports, ACC 5-HTT is related to trait aggression, and adjusting for factors related to proactive (callousness) and reactive (childhood trauma) aggression subtypes further resolves this relationship. Novel findings of the study include a better understanding of the association between regional 5-HTT availability and state aggression, and the involvement of VST 5-HTT with trait aggression, and with the anti-aggressive effects of fluoxetine.

Theorizing the Role of Dopaminergic Polymorphic Risk Alleles with Intermittent Explosive Disorder (IED), Violent/Aggressive Behavior and Addiction: Justification of Genetic Addiction Risk Severity (GARS) Testing.

Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward-deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant association with the D2 variant and a trend with the dopamine transporter variant. Results support our hypothesis and the involvement of at least two gene risk alleles with adolescent violent/aggressive behaviors. This study and the research presented in this paper suggest that violent/aggressive behaviors are associated with a greater risk of addiction, mediated via various genes linked to the BRC. This review provides a contributory analysis of how gene polymorphisms, especially those related to the brain reward circuitry, are associated with violent behaviors.

Cognitive-Behavioral Versus Supportive Psychotherapy for Intermittent Explosive Disorder: A Randomized Controlled Trial.

Few clinical trials have evaluated the efficacy of psychotherapy for Intermittent Explosive Disorder (IED). The present study tested the efficacy of a cognitive behavioral intervention (versus supportive psychotherapy) among adults with IED. In this randomized clinical trial, 44 participants with IED (22 men and 22 women) aged 20-55 years completed twelve 50-minute individual sessions of either a multi-component cognitive behavioral intervention for IED (n = 19) or a time equated supportive psychotherapy (n = 25). At baseline, posttreatment, and 3-month follow-up, all participants received the Overt Aggression Scale-Modified, which was conducted by an interviewer who was blind to the participant's study condition. During these visits, participants also completed self-report measures of relational aggression (Self-Report of Relational Aggression and Social Behavior), anger (State-Trait Anger Expression Inventory-2), cognitive biases (e.g., Social Information Processing Questionnaire Attribution and Emotional Response Questionnaire), and associated symptoms (e.g., Beck Depression Inventory). Primary study outcomes were aggressive behavior and anger. Though participants in both treatments tended to improve over time, the cognitive behavioral intervention was superior to supportive psychotherapy in decreasing aggressive behavior and relational aggression. These findings support the efficacy of a multicomponent cognitive behavioral intervention in treating aggression in IED.

Pharmacotherapy of impulse control disorders: A systematic review.

There are currently no evidence-based treatment recommendations for impulse control disorders, which include intermittent explosive disorder (IED), kleptomania and pyromania. Therefore, this systematic review sought to identify all randomized controlled trials (RCTs) that investigated pharmacological treatments for impulse control disorders, to evaluate their efficacy and tolerability. Searches were conducted within MEDLINE, PsychINFO, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eight studies were included, six investigated pharmacotherapies for IED, while two investigated management for kleptomania. For the treatment of IED, oxcarbazepine and fluoxetine were the most efficacious. Importantly, divalproex was not superior to placebo in decreasing IED symptoms and was associated with significant adverse effects. In the treatment of kleptomania, only naltrexone was effective. The existing data suggest that the pharmacological treatment for impulse control disorders is an understudied area of psychiatry. Much of the current research on impulse control disorders focuses on management with anticonvulsants and antidepressants. Further studies conducted on these interventions in this population may yield promising results.

A latent class analysis of intermittent explosive disorder symptoms.

Intermittent explosive disorder (IED), the sole diagnosis in the DSM-5 for which the cardinal symptom is recurrent affective aggressive outbursts, is a common and substantially impairing disorder. IED is also associated with several cognitive and affective impairments. However, little is known about the heterogeneity of the disorder and how this may correspond to aggression severity and related adverse outcomes. The current study employed a latent class analysis (LCA) among individuals diagnosed with lifetime DSM-5 IED to derive distinct subgroups that differed in the quality and/or frequency of cognitive-affective symptoms. These subgroups were then externally validated on a number of adverse outcomes. Statistical and clinical indicators supported a four-class model. Classes were distinguished mainly by the level of emotion dysregulation participants endorsed, with two moderate emotion dysregulation classes differing on their emotional information processing and impulsive tendencies. The external validation analysis revealed that classes differed in terms of various adverse outcomes (e.g., interpersonal problems, life satisfaction, suicide risk). Overall, the present study suggests distinct cognitiveaffective symptom profiles among those with IED that differ meaningfully with regard to risk for adverse outcomes. These findings provide evidence of the heterogeneity within IED and may suggest a more personalized therapeutic approach to patients with IED.

Mapping the neurocircuitry of impulsive aggression through the pharmacologic review of anti-impulsive aggressive agents.

Impulsive aggression, in contradistinction to premeditated aggression in humans or predatory aggression in animals, corresponds to defensive aggression in animal models. At the core of the neurocircuitry of impulsive aggression, from murine to feline to human species, it is the medial amygdala-mediobasal hypothalamus-dorsal periaqueductal gray pathway. Here, we update current knowledge on the neurocircuitry of impulsive aggression by placing the neurocircuitry and its neurophysiological substrates into the top-down/bottom-up hypothesis of impulsive aggression. We then reverse the neurotranslational approach, which applies neuroscience to developing therapeutic drugs, and apply current understanding of potential mechanisms of anti-impulsive aggression agents to further clarify, at least heuristically and hypothetically, the dynamic biochemical components of the neurocircuitry of impulsive aggression. To do this, we searched the medical literature for studies attempting to clarify the neurobiological and neurochemical effects of the five most widely studied anti-impulsive aggressive agents, particularly as they pertain to the top-down/bottom-up hypothesis. Multiple different mechanisms are discussed, all of which fitting in the hypothesis by way of either promoting the "top-down" part (i.e., enhancing inhibitory neurotransmitters), or suppressing the "bottom-up" part (i.e., decreasing excitatory neurotransmitters). The hypothesis appears consistent with the current psychopharmacological understanding of these agents, as well as to account for the likely multifactorial etiology of the condition. Limitations of the hypothesis and future directions are finally discussed.

Assessment of subjective sleep quality and issues in aggression: Intermittent Explosive Disorder compared with psychiatric and healthy controls.

BACKGROUND: While prior research has linked clinical sleep issues and aggression, little is known about how clinical sleep issues among individuals with Intermittent Explosive Disorder (IED), which is characterized by a pervasive pattern of impulsive aggression and associated with consequences across multiple life-domains. The present study aims to examine clinical sleep issues among individuals with IED in contrast to individuals with other psychopathology and healthy controls. METHODS: 257 adults, including 100 healthy controls, 85 psychiatric controls and 72 individuals with IED, took part in this study. Participants completed the Structured Clinical Interview for DSM-V Diagnoses, Assessment of clinical sleep issues included the Pittsburgh Sleep Quality Inventory (PSQI), obstructive sleep apnea (OSA) screening, and the Epworth Sleepiness Scale (ESS) as well as assessments of aggression and impulsivity. RESULTS: IED study participants reported significantly worse sleep quality, increased sleep latency, greater daytime sleepiness and symptoms of OSA. Daytime sleepiness and sleep quality was correlated with impulsivity and aggression. CONCLUSIONS: This study suggests that individuals with IED have clinically relevant sleep anomalies, and that these are directly associated with measures of impulsivity and aggression. Clinicians treating aggressive individuals are advised to assess and treat such individuals for sleep issues.

Gender Moderates the Association Between Exposure to Interpersonal Violence and Intermittent Explosive Disorder Diagnosis.

Exposure to interpersonal violence (EIV) is a prevalent risk-factor for aggressive behavior; however, it is unclear whether the effect of EIV on clinically significant aggressive behavior is similar across gender. We examined whether gender moderates the association between experiencing and witnessing interpersonal violence and the diagnosis of intermittent explosive disorder (IED). We also examined potential pathways that might differentially account for the association between EIV and IED in men and women, including emotion regulation and social information processing (SIP). Adult men and women (N = 582), who completed a semistructured clinical interview for syndromal and personality disorders, were classified as healthy controls (HC; n = 118), psychiatric controls (PC; n = 146) or participants with an IED diagnosis (n = 318). Participants also completed the life history of experienced aggression (LHEA) and life history of witnessed aggression (Lhwa) structured interview and self-report measures of emotion regulation and SIP. Men reported more EIV over the lifetime. In multiple logistic regression analysis, experiencing and witnessing aggression within the family and experiencing aggression outside the family were associated with lifetime IED diagnosis. We found that the relationship between EIV and IED was stronger in women than in men. Affective dysregulation mediated certain forms of EIV, and this relation was observed in both men and women. SIP biases did not mediate the relation between EIV and IED. EIV across the lifespan is a robust risk factor for recurrent, clinically significant aggressive behavior (i.e., IED). However, the relationship between EIV and IED appears to be stronger in women. Further, this relation appears partially mediated by affective dysregulation.

Neural responses to induced emotion and response to social threat in intermittent explosive disorder.

BACKGROUND: Individuals with intermittent explosive disorder (IED) are reported to exhibit amygdala (AMYG) hyper-activation to anger faces during functional magnetic resonance imaging (fMRI).  However, it remains unknown if emotional experience is different in study participants with IED compared with healthy controls (HC).  Thus, we examined the comparative effect of pleasant and unpleasant IAPS pictures in IED and HC individuals. METHOD: Eighty study participants (40 IED and 40 HC) underwent fMRI scanning while viewing blocks of angry and happy faces and while viewing blocks of pleasant and unpleasant pictures from the International Affective Picture System (IAPS). RESULTS: Compared with HC participants, IED participants exhibited greater AMYG responses to angry, but not happy, faces; IED and HC participants, however, did not differ in AMYG responses to pleasant or unpleasant IAPS pictures.  There were no group differences in Orbital-Frontal Cortical (OFC) responses to emotional faces or IAPS pictures other than a significantly higher OFC response pleasant, compared with unpleasant, IAPS pictures. CONCLUSION: These findings suggest that, compared with healthy individuals, those with IED have a hypersensitive amygdala to social-emotional threat but that this characteristic does not extend to neural responses related to the experience of emotion in the context of the paradigms tested.

Posterior hypothalamus as a target in the treatment of aggression: From lesioning to deep brain stimulation.

Intermittent explosive disorder can be described as a severe "affective aggression" condition, for which drugs and other supportive therapies are not fully effective. In the first half of the 19th century, experimental studies progressively increased knowledge of aggressive disorders. A neurobiologic approach revealed the posterior hypothalamic region as a key structure for the modulation of aggression. In the 1960s, patients with severe aggressive disorder, frequently associated with intellectual disability, were treated by bilateral stereotactic lesioning of the posterior hypothalamic area, with efficacy. This therapy was later abandoned because of issues related to the misuse of psychosurgery. In the last 2 decades, however, the same diencephalic target has been selected for the reversible treatment by deep brain stimulation, with success. This chapter presents a comprehensive approach to posterior hypothalamic surgery for the treatment of severely aggressive patients and discusses the experimental steps that allowed this surgical target to be selected. Surgical experiences are reported, together with considerations on target features and related encephalic circuits.

Directional Deep Brain Stimulation of the Posteromedial Hypothalamus for Refractory Intermittent Explosive Disorder: A Case Series Using a Novel Neurostimulation Device and Intraoperative Microdialysis.

BACKGROUND: Intermittent explosive disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behavior. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. We sought to evaluate efficacy and safety of pHyp-DBS using 8-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. METHODS: This was a prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with 8-contact directional electrodes. Follow-up was performed at 3, 6, and 12 months after surgery. RESULTS: Four patients (3 men, mean age 27 ± 2.8 years) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one had a co-diagnosis of infantile autism, and the fourth presented with drug-resistant epilepsy. There was a marked increase in the levels of gamma-aminobutyric acid and glycine during intraoperative stimulation. The average improvement in aggressive behavior in the last follow-up was 6 points (Δ: 50%, P = 0.003) while also documenting an important improvement of the Short Form Health Survey in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. CONCLUSIONS: This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with rIED and to demonstrate the corresponding mechanism of action through increases in gamma-aminobutyric acid and glycine concentration in the pHyp.

Evidence for the taxonic latent structure for DSM-5 intermittent explosive disorder in adults.

BACKGROUND: Identification of individuals with clinically significant aggressive behavior is critical for the prevention and management of human aggressive behavior. A previous population-based taxometric study reported that the Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) intermittent explosive disorder (IED) belongs to its own discrete class (taxon) rather than existing along a continuum. METHODS: This study sought to extend previous population-based findings in a clinical research sample of adults with DSM-5 IED (n = 346), adults with non-aggressive DSM-5 disorders (n = 293), and adults without any DSM-5 disorder (n = 174), using standardized assessments of DSM-5 diagnoses, aggression, and other related measures not available in past studies. RESULTS: Analyses revealed a taxonic latent structure that overlapped with the DSM-5 diagnosis of IED. Within the sample, taxon group members had higher scores on a variety of measures of psychopathology than did the complement members of the sample. Comorbidity of other diagnoses with IED did not affect these results. CONCLUSION: These findings support the proposition that DSM-5 IED represents a distinct behavioral disorder rather than the severe end of an aggressive behavior continuum.

The association between adverse childhood experiences and mental health problems in young offenders.

High rates of adverse childhood experiences (ACEs, e.g., abuse and neglect) have been found in young offenders. Furthermore, ACEs seem to increase the risk of developing relevant mental health problems, in non-offending juveniles and adults. However, this association has only seldomly been addressed in offending juveniles and young adults. The present study aimed at evaluating the prevalence of ACEs and mental health problems as well as their association within a sample of male and female young offenders. Altogether, 161 adolescent and young adult offenders (16.8% females) from the youth detention center Worms (Germany) filled out questionnaires concerning ACEs and mental health problems with a focus on attention-deficit/hyperactivity disorder and intermittent explosive disorder. Considerable rates of mental health problems were found, e.g., a prevalence of 35.9% was found for intermittent explosive disorder. Furthermore, a greater proportion of the female offenders fell into the clinically significant category for somatic complaints, anxiety/depression, and attention problems than the male offenders. Female young offenders also reported more frequently about all forms of ACEs compared to the male offenders. Latent class analysis defined three subtypes of young offenders depending on their individual ACE patterns: (1) low ACEs, (2) mainly neglectful ACEs, and (3) multiple ACEs. ACEs were significantly associated with the occurrence of both internalizing and externalizing mental health disturbances, with the multiple-ACE subtype being most likely to report about significant mental health problems. The results of the present study point towards the relevance to routinely assess ACEs in young offenders to identify possible precursors of mental health problems and of future criminal behaviors.

Directional deep brain stimulation of the posteromedial hypothalamus for refractory intermittent explosive disorder: a case series using a novel neurostimulation device and intraoperative microdialysis

Intermittent Explosive Disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behaviour. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. Objective To evaluate efficacy and safety of pHyp-DBS using eight-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. Methods A prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with eight-contact directional electrodes. Follow-up was performed at 3, 6 and 12 months after surgery. Results Four patients (3 men, mean age 27 ± 2.8 yr) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one has co-diagnosis of infantile autism and the fourth presents with drug-resistant epilepsy. There was a marked increase in the levels of GABA and glycine during intraoperative stimulation. The average improvement in aggressive behaviour in the last follow-up was 6 points (Δ: 50%, p= 0.003) while also documenting an important improvement of the SF-36 in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. Conclusions This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with refractory Intermittent Explosive Disorder and to demonstrate the corresponding mechanism of action through increases in GABA and glycine concentration in the pHyp.

Intermittent explosive disorder subtypes in the general population: association with comorbidity, impairment and suicidality.

AIMS: Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment. METHODS: IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment. RESULTS: The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people ('hurt people only' and 'destroy property and hurt people'), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults. CONCLUSIONS: The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.

Gray Matter Deficits and Dysfunction in the Insula Among Individuals With Intermittent Explosive Disorder.

Although numerous neuroimaging studies have evaluated the characteristics of intermittent explosive disorder (IED), studies on the structural alterations and focal dysfunction in the brain in this condition are limited. This study aimed to identify gray matter deficits and functional alterations in individuals with IED using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) analyses. Fifteen men with IED and 15 age- and sex-matched healthy controls participated in this study. Gray matter volume and brain activation while viewing the anger-inducing films were measured using 7T MRI. VBM results indicated that individuals with IED had significantly reduced gray matter volume in the insula, amygdala, and orbitofrontal area, relative to controls. Gray matter volume in the left insula was negatively correlated with composite aggression scores. fMRI results demonstrated that relative to healthy controls, individuals with IED showed greater activation in the insula, putamen, anterior cingulate cortex, and amygdala during anger processing. Left insular activity was positively correlated with composite aggression scores. Collectively, these findings suggest that structural and functional alterations in the left insula are linked to IED; this provides insight into the neural mechanisms underlying IED.