Intermittent Explosive Disorder Subjects Research Articles

T68. Seed Based Correlation Analysis of Amygdala and Orbitofrontal Regions in Resting State Activity of an Intermittent Explosive Disorder Population

Intermittent Explosive Disorder (IED) has been studied using task-based functional magnetic resonance imaging. Amygdala and orbitofrontal (OFC) brain regions are altered during emotional processing in IED subjects. However, no research has assessed differences in resting state activity to determine whether intrinsic neural activity in IED is altered.

Comorbidity of personality disorder with intermittent explosive disorder

There is ambiguity in how recurrent anger and aggression are accounted for by psychiatric nosology. One area of uncertainty is the extent to which Intermittent Explosive Disorder (IED) overlaps with and is distinct from Personality Disorder (PD). Accordingly, we conducted a study of individuals with IED and PD in order to understand the nature of comorbidity relationships seen across these two areas of psychopathology. One-thousand-five-hundred-twenty-one adults were studied (441 Healthy Controls (HC), 430 Psychiatric Controls (PC), and 650 IED subjects) and assessed for DSM-5 psychiatric disorders, life history of aggressive behavior, trait aggression, state and trait anger reactivity, and impulsivity. While nearly half of IED study participants had a comorbid PD diagnosis, nearly half with a Cluster B PD, almost as many had other personality disorders. IED predicted anger symptoms and history of aggressive behavior above and beyond a PD diagnosis. Comorbidity between IED and either Antisocial (AsPD) or Borderline (BPD) PD was associated with the highest levels of aggressive behavior. However, having IED comorbid with either AsPD and/or BPD PD was not associated with higher levels of impulsivity. Underlying personality traits related to anger, affect, and social behavior, but not identity disturbance, contribute to the shared symptom profile of IED and PD. IED is usually comorbid with PD, but does not have a unique relationship with any single PD. When comorbid with PD, a diagnosis of IED predicts more severe anger and aggression, but not necessarily increased impulsivity. These results suggest that IED and PD diagnoses retain clinical utility when made in cases meeting criteria for both.

Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis

BackgroundIntermittent explosive disorder is defined as a recurrent, problematic, and impulsive aggression that affects 3% to 4% of the US population. While behavioral genetic studies report a substantial degree of genetic influence on aggression and impulsivity, epigenetic mechanisms underlying aggression and intermittent explosive disorder are not well known.MethodsThe sample included 44 subjects (22 with a DSM-5 diagnosis of intermittent explosive disorder and 22 comparable subjects without intermittent explosive disorder). Peripheral blood DNA methylome was profiled using the Illumina Infinium HumanMethylation450 Beadchip. Intermittent explosive disorder-associated genome-wide DNA methylation changes were analyzed using the CpGassoc R package, with covariates age, sex, and race being adjusted. A gene-based functional enrichment analysis was performed to identify pathways that were overrepresented by genes harboring highly differentially methylated CpG sites.ResultsA total of 27 CpG sites were differentially methylated in IED participants (P<5.0×10–5), but none reached genome-wide significant threshold. Functional enrichment analysis revealed that genes mapped by these CpG sites are involved in the inflammatory/immune system, the endocrine system, and neuronal differentiation.ConclusionsConsistent with our previous studies showing an association of inflammatory response with aggressive behavior in intermittent explosive disorder subjects, our gene-based pathway analysis using differentially methylated CpG sites supports inflammatory response as an important mechanism involved in intermittent explosive disorder and reveals other novel biological processes possibly associated with intermittent explosive disorder.

Differential fMRI BOLD responses in amygdala in intermittent explosive disorder as a function of past Alcohol Use Disorder

BackgroundIndividuals with intermittent explosive disorder (IED) were previously found to exhibit amygdala (AMYG) hyperactivation to anger faces during functional magnetic resonance imaging (fMRI). However, acute alcohol consumption, and/or life history of alcoholism, may blunt amygdala responses to negative emotional stimuli. Thus, we examined the influence of a past history of DSM-5 Alcohol Use Disorder (AUD) on the fMRI BOLD AMYG response to anger faces in IED. MethodForty-two IED participants, 18 with a past history of AUD (IED+AUD) and 24 without Past AUD (IED), and 32 healthy control (HC) participants, underwent fMRI scanning while viewing blocks of angry, fearful, and happy faces. ResultsCompared to HC and IED+AUD participants, IED subjects exhibited greater AMYG responses to angry, but not to fear or happy, faces in the left AMYG. There were no group differences in responses to anger, fear, or happy, faces in the OFC. ConclusionThese findings suggest the possibility of a longstanding effect of AUD on AMYG response in IED to anger-related stimuli and highlight the possibility that history of AUD should be considered as an important factor in the interpretation of fMRI studies involving the AMYG response to negative emotional stimuli.

Amygdala hyperactivation to angry faces in intermittent explosive disorder

BackgroundIndividuals with intermittent explosive disorder (IED) were previously found to exhibit amygdala hyperactivation and relatively reduced orbital medial prefrontal cortex (OMPFC) activation to angry faces while performing an implicit emotion information processing task during functional magnetic resonance imaging (fMRI). This study examines the neural substrates associated with explicit encoding of facial emotions among individuals with IED. MethodTwenty unmedicated IED subjects and twenty healthy, matched comparison subjects (HC) underwent fMRI while viewing blocks of angry, happy, and neutral faces and identifying the emotional valence of each face (positive, negative or neutral). We compared amygdala and OMPFC reactivity to faces between IED and HC subjects. We also examined the relationship between amygdala/OMPFC activation and aggression severity. ResultsCompared to controls, the IED group exhibited greater amygdala response to angry (vs. neutral) facial expressions. In contrast, IED and control groups did not differ in OMPFC activation to angry faces. Across subjects amygdala activation to angry faces was correlated with number of prior aggressive acts. ConclusionsThese findings extend previous evidence of amygdala dysfunction in response to the identification of an ecologically-valid social threat signal (processing angry faces) among individuals with IED, further substantiating a link between amygdala hyperactivity to social signals of direct threat and aggression.

Inflammatory markers and chronic exposure to fluoxetine, divalproex, and placebo in intermittent explosive disorder

Intermittent Explosive Disorder (IED) is a disorder of impulsive aggression affecting 4–7% of the U.S. population during some period of life. In addition to other biological correlates, elevations of plasma inflammatory markers have been reported in IED, compared with control, subjects. In this study we sought to explore if treatment exposure to anti-aggressive agents, compared with placebo, would be associated with a reduction in circulating levels of inflammatory markers. Thirty IED subjects, from a 12-week, double-blind, randomized, placebo-controlled trial of fluoxetine and divalproex, in which both pre- and post-treatment levels of C-Reactive Protein (CRP), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were obtained. Efficacy measures included the Overt Aggression Scale-Modified (OAS-M) score for Aggression and for Irritability, rate of Clinical Global Impression of Improvement (CGI-I), and rate of IED Remitters at study completion. As compared to placebo, neither fluoxetine nor divalproex reduced any of the measures of aggression. In addition, levels of CRP and pro- and anti-inflammatory cytokines showed no changes from pre- to post-treatment for any treatment condition. Correlations between pre- and post- treatment plasma CRP/cytokines were substantial (mean r=0.71, r2=0.50, p<0.001). Overall, circulating markers of inflammation markers were unaffected by treatment with fluoxetine or divalproex, consistent with the absence of change in measures of impulsive aggression.

Morphometric analysis of amygdla and hippocampus shape in impulsively aggressive and healthy control subjects

BackgroundImpulsive aggressive behavior is thought to be facilitated by activation of the limbic brain, particularly the amygdala and hippocampus., Functional imaging studies suggest abnormalities in limbic brain activity during emotional information processing in impulsively aggressive subjects with Intermittent Explosive Disorder (IED). It is not known if IED is associated with altered amygdala and hippocampus volume and shape. MethodsWe examined the volume and shape of the amygdala–hippocampal complex, using morphometric analysis of high resolution structural 3T MR scans in healthy control (HC: n = 73) subjects without history of Axis I or II psychiatric conditions and in subjects with IED (n = 67). ResultsWhile no volume differences were observed between HC and IED subjects, a significant level of morphometric deformation, suggestive of cell loss, in both amygdala and hippocampal structures was observed bilaterally in IED subjects. Analysis of a canonical variable that used the first 10 eigenvectors from both sides of the brain revealed that these morphometric deformations in the IED subjects were not due the presence of confounding variables or to comorbidities among IED subjects. ConclusionsThese data reveal that IED is associated with a significant loss of neurons in both the amygdala and hippocampus. These changes may play a role in the functional abnormalities observed in previous fMRI studies and in the pathophysiology of impulsive aggressive behavior.

Intermittent Explosive Disorder and aversive parental care

Parental bonding has been shown to have lasting impacts on the psychological development of children. Despite a growing body of research examining trauma as it relates to Intermittent Explosive Disorder (IED), no prior research has examined the relationship between parental bonding and IED. Six hundred fifty eight subjects were studied and categorized into one of three groups: Normal Control (no history of current or lifetime Axis I or Axis II disorder), Psychiatric Control (current and/or lifetime Axis I and/or Axis II disorders without IED), and IED (met current and/or lifetime criteria for IED). Self-reported parental care was assessed using the Parental Bonding Inventory (PBI). PBI Care scores were lowest among IED subjects, which were lower than among Psychiatric Control subjects, which were lower than among Normal Control subjects. PBI Control scores were highest among IED and Psychiatric Control subjects, which were higher than among Normal Control subjects. The diagnostic group differences in PBI Care/PBI Control scores were not impacted by the number of Axis I/II diagnoses. The findings in this study expand the link between childhood trauma exposure, violent behavior, and IED. This is the first report of an association of IED with an aversive childhood parenting environment.

History of childhood maltreatment in Intermittent Explosive Disorder and suicidal behavior

Intermittent Explosive Disorder (IED) is a relatively common disorder of impulsive aggression that typically emerges by adulthood. Maltreatment in childhood (CM) may contribute to the development of IED, but little is known about the association between CM and IED, including about how subtypes of CM may specifically relate to IED. This study aimed to test the association between CM and IED diagnosis. A second aim was to examine history of CM in suicide attempters, and to explore whether impulsivity and aggression account for the relationship between CM and suicide attempt (SA). Adults with Intermittent Explosive Disorder (IED; n = 264), with non-IED psychiatric (Axis I or II) disorders (psychiatric controls; PC; n = 199), and with no psychiatric disorder (healthy control subjects; HC; n = 185) were assessed for history of childhood maltreatment, aggression, impulsivity, and history of SA. IED subjects reported significantly greater CM compared to PC and HC subjects, and suicide attempters (n = 62) reported greater CM compared to non-attempters (n = 586). Physical abuse in childhood was independently associated with IED, while sexual abuse and emotional abuse were independently associated with SA. Impulsivity and aggression were potential mediators of the relationship between physical abuse and IED and emotional abuse and SA, but sexual abuse was associated with SA independently of aggression and impulsivity. The results suggest pathways by which environmental factors may influence impulsivity and aggression and, in turn, clinically significant self- and other-directed aggression.

99. Plasma markers of inflammation are elevated in intermittent explosive disorder and as a function of aggression in human subjects

Behavior can influence immune function, inflammatory activity, and psychological functioning; these relationships are often bi-directional. Aggressive behavior is associated with elevations in inflammatory mediators in animals, but few studies have examined these connections in humans. The present study explored relationships between aggressive behavior and serum levels of interleukin-6 (IL-6), soluble interleukin-1B receptor type II (IL1BrII), and C-reactive protein (CRP) in patients with Intermittent Explosive Disorder (IED), controls with Axis I and/or Axis II, disorders (Psychiatric Controls: PC), and subjects with no evidence of psychopathology (Healthy Controls: HC). Inflammatory markers were highly correlated with aggressive behavior, and impulsivity and aggression were highly related in all subjects ( p < .05). Each of the three inflammatory markers was correlated with life history of aggression (LHA) for all groups ( p s < .05). Among the psychiatric (PC and IED) subjects, higher inflammatory markers were associated with life history of suicidal attempts although further analysis showed that this was accounted for by LHA. Finally, IED subjects had significantly elevated levels of all three inflammatory markers compared to PC and HC ( p s < .05). These results suggest a relationship between aggressive behavior and inflammatory activity which is especially notable in patients with IED compared to PC and HC. Additional work is necessary to elucidate the significance of these findings for not only health and immunity but also for the management and treatment of IED.

Language and the Modulation of Impulsive Aggression

Language and the Modulation of Impulsive Aggression

Prevalence of suicidal and self-injurious behavior among subjects with intermittent explosive disorder

The prevalence of suicidal attempts and self-injurious behavior among 376 subjects diagnosed with Intermittent Explosive Disorder (IED) was assessed via structured interviews. Results showed 16% of IED subjects reported self-aggression, with 12.5% reporting suicide attempts and 7.4% reporting non-lethal self-injurious behaviors. Additional risk factors were identified.

Intermittent explosive disorder-integrated research diagnostic criteria: Convergent and discriminant validity

Research on intermittent explosive disorder (IED) has been hindered by vague and restrictive DSM-IV diagnostic criteria. Integrated research criteria have been developed for IED (IED-IR) that address the DSM-IV criteria’s shortcomings. The purpose of this study was to examine the convergent and discriminant validity of the IED-IR criteria set by comparing adults meeting these criteria ( n = 56) to healthy controls ( n = 56) and to individuals with an Axis I major mental disorder ( n = 33) or an Axis II personality disorder ( n = 22) diagnoses on measures of aggression (self-report and behavioral) and global functioning. IED-IR individuals demonstrated higher levels of aggression compared to the other three groups, and were rated as more impaired than the healthy control and Axis I individuals. Subgroup analyses showed that IED-IR subjects who did not meet DSM IED criteria did not differ from DSM IED subjects on self-report measures of aggressiveness or global functioning. Furthermore, the IED-IR subjects evidenced more behavioral aggression than their DSM-IED counterparts.

Regional variations in admission rates for schizophrenia in England: A comparison of geographic and social factors

Intermittent Explosive Disorder (IED) is a relatively common disorder of impulsive aggression that typically emerges by adulthood. Maltreatment in childhood (CM) may contribute to the development of IED, but little is known about the association between CM and IED, including about how subtypes of CM may specifically relate to IED. This study aimed to test the association between CM and IED diagnosis. A second aim was to examine history of CM in suicide attempters, and to explore whether impulsivity and aggression account for the relationship between CM and suicide attempt (SA). Adults with Intermittent Explosive Disorder (IED; n = 264), with non-IED psychiatric (Axis I or II) disorders (psychiatric controls; PC; n = 199), and with no psychiatric disorder (healthy control subjects; HC; n = 185) were assessed for history of childhood maltreatment, aggression, impulsivity, and history of SA. IED subjects reported significantly greater CM compared to PC and HC subjects, and suicide attempters (n = 62) reported greater CM compared to non-attempters (n = 586). Physical abuse in childhood was independently associated with IED, while sexual abuse and emotional abuse were independently associated with SA. Impulsivity and aggression were potential mediators of the relationship between physical abuse and IED and emotional abuse and SA, but sexual abuse was associated with SA independently of aggression and impulsivity. The results suggest pathways by which environmental factors may influence impulsivity and aggression and, in turn, clinically significant self- and other-directed aggression.