Comparing behavioral measures of aggression in the laboratory: Taylor Aggression Paradigm versus Point-Subtraction Aggression Paradigm.

Aggression refers to a wide range of behaviors with lasting individual and societal consequences. Recurrent, unplanned aggressive behavior is the core diagnostic criterion for intermittent explosive disorder (IED). In this study, we compared two behavioral measures of aggression in the laboratory: the Taylor Aggression Paradigm (TAP) and the Point-Subtraction Aggression Paradigm (PSAP). This sample (n = 528) included community participants who met DSM-5 criteria for IED (n = 156), met DSM-5 criteria for a nonaggressive psychiatric disorder (n = 205), or did not meet DSM-5 criteria for any psychiatric disorder (n = 167). All participants completed the TAP, a single-session PSAP, and relevant self-report measures. MANOVA analyses demonstrated differences between IED participants and nonaggressive participants; however, these group differences were no longer significant for the PSAP after including demographic variables. Correlation analyses found that the TAP and PSAP were positively related to one another and the composite variables associated with aggressive behavior (i.e., history of aggression, impulsivity, and propensity to experience anger) and; dependent correlations revealed that past aggression and trait anger were more strongly related to the TAP. Differences in TAP and PSAP outcomes may be partially attributed to operationalizations of aggression and methods of aggression and provocation. Further, as aggressive and nonaggressive participants differed on the PSAP somewhat mirroring the TAP, our results add to growing evidence of the validity of a single-session PSAP; further research is needed to fully establish single-session PSAP as a laboratory aggression task compared to the multi-session PSAP.

Defining the p-factor: an empirical test of five leading theories.

BACKGROUND: Despite statistical evidence of a general factor of psychopathology (i.e., p-factor), there is little agreement about what the p-factor represents. Researchers have proposed five theories: dispositional negative emotionality (neuroticism), impulsive responsivity to emotions (impulsivity), thought dysfunction, low cognitive functioning, and impairment. These theories have primarily been inferred from patterns of loadings of diagnoses on p-factors with different sets of diagnoses included in different studies. Researchers who have directly examined these theories of p have examined a subset of the theories in any single sample, limiting the ability to compare the size of their associations with a p-factor. METHODS: In a sample of adults (N = 1833, Mage = 34.20, 54.4% female, 53.3% white) who completed diagnostic assessments, self-report measures, and cognitive tests, we evaluated statistical p-factor structures across modeling approaches and compared the strength of associations among the p-factor and indicators of each of these five theories. RESULTS: We found consistent evidence of the p-factor's unidimensionality across one-factor and bifactor models. The p-factor was most strongly and similarly associated with neuroticism (r = .88), impairment (r = .88), and impulsivity (r = .87), χ2(1)s < .15, ps > .70, and less strongly associated with thought dysfunction (r = .78), χ2(1)s > 3.92, ps < .05, and cognitive functioning (r = -.25), χ2(1)s > 189.56, ps < .01. CONCLUSIONS: We discuss a tripartite definition of p that involves the transaction of impulsive responses to frequent negative emotions leading to impairment that extends and synthesizes previous theories of psychopathology.

Childhood and parental characteristics of adults with DSM-5 intermittent explosive disorder compared with healthy and psychiatric controls.

BACKGROUND: Intermittent Explosive Disorder (IED) is a disorder primarily of aggression, defined by recurrent behavioral outbursts out of proportion to provocations or stressors. IED first appears in childhood and adolescence. This study examines the underlying childhood environment of those with IED, particularly familial and school-related factors. METHODS: Adult participants from a larger study completed diagnostic assessments and a battery of self-report measures. Group assignment was based on the assessment: 1) IED diagnosis; 2) non-IED psychiatric diagnosis; and 3) no significant psychiatric history. Groups were compared on factors of parental demographics, intrafamilial aggression, lifetime syndromal and personality diagnoses, neurodevelopmental and learning difficulties, childhood peer relationships, and juvenile legal issues. RESULTS: Significant patterns emerged specific to IED for not being raised by both parents, greater physical aggression to participant, and greater degree of fighting with peers by age ten. LIMITATIONS: The retrospective, and cross-sectional, nature of the study, which prevent the making of causal inferences, and the basic nature of the questions asked of participants which limit a more nuanced interpretation of the data. A further limitation is bias associated with self-reported responses. CONCLUSIONS: Results suggest the prevalence childhood adversaries may be linked with IED; the childhood environment of those with IED likely is substantially more tumultuous than individuals with or without other psychiatric disorders.

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.

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.

Emotion attribution in intermittent explosive disorder.

BACKGROUND: Accurate recognition of the emotions of others is an important part of healthy neurological development and promotes positive psychosocial adaptation. Differences in emotional recognition may be associated with the presence of emotional biases and can alter one's perception, thus influencing their overall social cognition abilities. The present study aims to extend our collective understanding of emotion attribution abnormalities in individuals with Intermittent Explosive Disorder (IED). METHODS: Two-hundred and forty-two adults participated, separated into groups of those diagnosed with IED according to DSM 5 criteria, Psychiatric Controls (PC), and Healthy Controls (HC). Participants completed a modified version of the Emotional Attribution Task wherein they attributed an emotion to the main character of a short vignette. RESULTS: Participants with IED correctly identified anger stories and misattributed anger to non-anger stories significantly more often than PC and HC participants. They were also significantly less likely than HC participants to correctly identify "sad stories." LIMITATIONS: We utilized self-report assessments in a community-recruited sample. Replication in a clinical is suggested. CONCLUSIONS: Findings from this study support the validity of IED as a diagnostic entity and provide important information about how individuals with psychiatric disorders perceive and experience emotional cues.

5-HT2c agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study.

RATIONALE: Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsive aggression do not respond adequately to selective serotonin reuptake inhibitors and may require treatment with a direct 5-HT agonist. OBJECTIVES: To test the hypothesis that pretreatment with the selective 5-HT2c agonist, lorcaserin, can reduce aggressive responding in impulsively aggressive individuals. METHODS: Ten male and female adults were given lorcaserin (20 mg), or a matching placebo, in random order, on 2 days separated by at least 1 week. The Taylor aggression paradigm was used to assess aggressive responding, which was represented by mean shock setting administered to an opponent and by frequency of setting high and extreme shock levels to the opponent. RESULTS: Compared with placebo, lorcaserin attenuated provoked, but not unprovoked, aggression during the Taylor aggression paradigm. This was manifest by reduction in the frequency of selecting high and extreme levels of shock against the opponent. CONCLUSION: Lorcaserin may possess anti-aggressive properties that could prove useful in the treatment of impulsive aggressive behavior in human subjects. These data, thus, provide a rationale for a follow-up randomized clinical trial of lorcaserin in individuals with prominent histories of impulsive aggressive behavior.

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

Background: Intermittent 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. Methods: The 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. Results: A 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. Conclusions: Consistent 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.

Mild Traumatic Brain Injury and Aggression, Impulsivity, and History of Other- and Self-Directed Aggression.

Mild traumatic brain injury (mTBI) is highly prevalent, with an estimated occurrence in the United States of more than 1.3 million per year. While one consequence of mTBI is impulsive aggressive behavior, very few studies have examined the relationship between history of mTBI and aggressive behavior in impulsively aggressive individuals. The authors examined the relationship between history of mTBI in a healthy control group (HC; N=453), a control group with psychiatric disorders (PC; N=486), and individuals with intermittent explosive disorder (IED; N=695), a disorder of primary impulsive aggression. Results demonstrated that IED study participants were significantly more likely to have a history of mTBI (with or without history of a brief loss of consciousness [LOC]) compared with both HC and PC participants. A similar observation was made with regard to self-directed aggression (i.e., suicidal or self-injurious behavior), although group differences were only among those with mTBI with LOC. For both other- and self-directed aggression variables, the authors observed a stepwise increase in dimensional aggression and impulsivity scores across participants as a function of mTBI history. Given that impulsive aggressive behavior begins very early in life, these data are consistent with the hypothesis that lifelong presence of an impulsive aggressive temperament places impulsive aggressive individuals in circumstances that put them at greater risk for mTBI compared with other individuals with and without nonimpulsive aggressive psychopathology.

DSM-5 intermittent explosive disorder: Relationship with Disruptive Mood Dysregulation Disorder.

OBJECTIVE: This study was designed to estimate how many adults with DSM-5 Intermittent Explosive Disorder (IED) would also meet diagnostic criteria for Disruptive Mood Dysregulation Disorder (DMDD). This was done by examining how many individuals with IED would meet the DMDD criterion of being persistently angry in between impulsive aggressive outbursts. METHODS: The first one-hundred study participants diagnosed with DSM-5 IED in our clinical research program were included in this study. Two questions were added to the IED module from the Structured Clinical Interview for DSM-5 Disorders (SCID) inquiring about the duration of anger in between impulsive aggressive outbursts in IED study participants. Data regarding aggression, impulsivity, anger expression, and related dysphoric variables were also collected. RESULTS: The proportion of time spent as angry in between impulsive aggressive outbursts was <50% of the time (~35%) for the vast majority (92%) of study participants with DSM-5 IED. Despite this, persistently-angry (i.e., angry >50% time in between outbursts) IED study participants displayed no differences from not-persistently-angry IED study participants in dysphoric and aggression/impulsivity related variables. CONCLUSIONS: These data indicate that inter-outburst anger in those with IED is relatively brief and that such individuals do not generally display the kind of persistent anger that is a diagnostic feature of DMDD.

Development of a screening questionnaire for DSM-5 intermittent explosive disorder (IED-SQ).

OBJECTIVE: This study was designed to develop and test a screening approach to identify individuals with DSM-5 Intermittent Explosive Disorder (IED), a disorder of recurrent, problematic, impulsive aggression. METHODS: A screening approach to diagnose DSM-5 IED (IED-SQ) was developed by combining items related to life history of aggression and items related to the DSM-5 diagnostic criteria for IED. In study 1, the IED-SQ was studied in 72 adult participants; 33 that met DSM-5 criteria for lifetime IED and 39 that did not. In study 2, the IED-SQ was given to 740 undergraduates at a US university. Measures of aggression and anger expression and anger control were assessed in both studies. RESULTS: In study 1, the IED-SQ demonstrated strong concordance with the best estimate diagnoses (Kappa =.80) for lifetime IED by DSM-5 criteria and good test-retest reliability (kappa =0.71). In study 2, the IED-SQ identified 4.3% of the undergraduate sample as meeting DSM-5 criteria for lifetime IED, a rate comparable to that in recent epidemiological studies. Participants identified as meeting DSM-5 criteria for lifetime IED, in both studies, had higher aggression scores, and higher anger expression, and lower anger control scores, compared to participants that did not meet DSM-5 criteria for lifetime IED. CONCLUSIONS: These data suggest that the IED-SQ is a useful screening tool that can quickly identify the presence of IED by DSM-5 criteria in adults.

Intermittent explosive disorder and eating disorders: Analysis of national comorbidity and research samples.

OBJECTIVE: Clinical studies suggest comorbidity between eating disorders and aggressive behaviors. This study examined the pattern of comorbidity between intermittent explosive disorder (IED) and eating disorders (ED). METHODS: Data were analyzed from both the adult and adolescent samples of the National Comorbidity Survey-Replication (n = 19,430) and a clinical research sample (n = 1,642). RESULTS: Lifetime prevalence of Any ED was elevated in IED vs. non-IED for both the community and clinical research samples. Though anorexia nervosa displayed no relationship with IED in either sample, bulimia nervosa was associated with IED in the community sample and binge eating disorder was associated with IED in both the community and clinical research samples. Onset of IED preceded onset of Any ED in at least 70% of comorbid IED/ED cases in both community and clinical research samples. Associations of IED with Any ED and bulimia nervosa in the community sample, and associations of IED with binge eating disorder in the clinical research sample, remained significant after controlling for other psychiatric disorders. CONCLUSIONS: Individuals with IED are more likely to report lifetime prevalence of ED, particularly bulimic spectrum disorders. This finding, and the observation that the onset of IED occurs prior to the onset of ED in the majority of individuals, suggests that longitudinal studies are needed to clarify this relationship and determine whether IED is a risk factor for the development of ED. Early identification of individuals with IED or impulsive aggression may provide clinically useful information to determine most effective treatment interventions.

Development of a social emotional information processing assessment for adults (SEIP-Q).

An expanded self-report, vignette-based, questionnaire was developed to assess five components in a social emotional information processing model (SEIP: attribution, emotional response, response valuation, outcome expectancy, response efficacy, and response enactment), first in a population-based sample (n = 250) and, second in healthy control participants (n = 50) and in those with DSM-5 Intermittent Explosive Disorder (IED: n = 50). SEIP-Q vignettes depict, separately, both overtly aggressive and relationally aggressive as well as socially ambivalent scenarios. This expanded SEIP-Q assessment demonstrated good internal reliability, as well as convergent and discriminant validity, for all five SEIP components. IED participants differed from healthy controls in all SEIP-Q components. This expanded SEIP-Q assessment is thus proposed as a reliable and valid method for studying the various stages of SEIP in adult human subjects. Aggr. Behav. 43:47-59, 2017. © 2016 Wiley Periodicals, Inc.

Comorbid intermittent explosive disorder and posttraumatic stress disorder: Clinical correlates and relationship to suicidal behavior.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with both aggressive and suicidal behavior. Recent research suggests that the diagnosis of intermittent explosive disorder (IED), an impulse-control disorder characterized by repeated impulsive aggressive behavior, may help to identify individuals at risk for attempting suicide. Given the relationship between anger and PTSD, there is likely to be an increased prevalence of IED among individuals with PTSD; however, little is known about the overlap in these two disorders, including how individuals with comorbid IED and PTSD may differ from those with either disorder alone. The purpose of this study is to examine the clinical correlates of comorbid IED and PTSD and the contribution of these two disorders (among others) to lifetime suicide attempt and characteristics of suicidal behavior. METHOD: In a large sample of community research volunteers (N=1460), we compared individuals with PTSD, IED, and comorbid PTSD and IED on measures of current mood, trait aggression, and trait impulsivity. We also examined the contributions of PTSD, IED, and other syndromal and personality disorders to the prediction of lifetime aggression and lifetime suicide attempt, and their relationship to characteristics of suicide attempts, including level of intent, use of violent versus non-violent means, and the medical seriousness of the attempt. RESULTS: Comorbid PTSD and IED was associated with significantly elevated levels of depression, anxiety, anger, aggression, and impulsivity, as well as with high rates of comorbidity with other psychiatric disorders. IED (ß=.56, p<.001), but not PTSD, significantly and uniquely predicted lifetime aggressive behavior. Both IED and PTSD were associated with lifetime suicide attempt in multivariate analysis (ORs: 1.6 and 1.6, ps<.05). The results show that IED, when comorbid with PTSD, identifies a subgroup of individuals with particularly high levels of aggressive behavior and a high rate of suicide attempt (41.4% in this sample). CONCLUSION: These findings add support to the notion that the diagnosis of IED may aid in identifying individuals at risk for aggressive and suicidal behavior.

Cerebrospinal fluid inflammatory cytokines and aggression in personality disordered subjects.

BACKGROUND: Neurochemical studies have pointed to a modulatory role in human aggression for a variety of central neurotransmitters and neuromodulators such as cytokines. While animal studies of cytokines suggest an aggression-facilitating role for central cytokines, especially for interleukin-1ß and other cytokines, no cerebrospinal fluid studies of cytokines have yet been reported in regard to human aggression. METHODS: Basal lumbar cerebrospinal fluid samples were obtained from 38 physically healthy subjects with DSM-5 Personality Disorder and assayed for cerebrospinal fluid interleukin-6 (log IL-6) and cerebrospinal fluid soluble IL-1 Receptor II protein in the context of their relationship with measures of aggression. RESULTS: Cerebrospinal fluid soluble interleukin-1 Receptor II (r=.35, r(2) = .12, P= .03), but not log interleukin-6 (r = -.05, r(2) = .00, P= .76), levels were positively correlated with a composite measure of aggression. Adding relevant covariates, including cerebrospinal fluid levels of serotonin and dopamine metabolites, to the statistical model doubled the strength of this relationship (partial r = .54, r(2) = .29, P= .002). No relationship was seen with history of suicidal behavior or with any measure of impulsivity, negative affectivity, or of general dimensions of personality. CONCLUSION: These data suggest a positive relationship between at least one inflammatory cytokine in the central nervous system and aggression in human subjects. This finding adds to the complex picture of the central neurochemistry of impulsive aggression in human subjects.

Cerebrospinal fluid and plasma C-reactive protein and aggression in personality-disordered subjects: a pilot study.

C-reactive protein (CRP), in the plasma, serves as a marker of systemic inflammation and has been shown to correlate with history of actual aggressive behavior, and as a personality trait of aggressive tendency, in human subjects. This pilot study was conducted to determine if plasma CRP levels are correlated with cerebrospinal fluid levels (CSF CRP) and if CSF CRP also correlates with aggression. If so, this would suggest a role for central inflammatory processes in human aggression. Both plasma and basal lumbar CSF samples were obtained from 17 subjects with DSM-5 personality disorder and assayed for CRP. Plasma and CSF CRP levels were correlated (r = 0.65, p = 0.005) and each correlated with aggression (Plasma: r = 0.53, p = 0.029; CSF: r = 0.84, p < 0.001). When considered simultaneously, CSF CRP, but not plasma CRP, uniquely correlated with aggression. No relationship was seen with other measures of psychopathology. These data suggest a positive relationship between central nervous system CRP and aggression in humans.

Serotonin and impulsive aggression.

Aggression is a behavior with evolutionary origins, but is often both destructive and maladaptive in today's society. Research over the past several decades has confirmed the involvement of neurotransmitter function in aggressive behavior. This research has centered around the "serotonin hypothesis." As this literature continues to grow, guided by pre-clinical research and aided by the application of increasingly sophisticated neuroimaging methodology, a more complex picture has emerged. As current pharmacological and therapeutic interventions are effective but imperfect, it is hoped that new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behavior.

Emotion regulation deficits in intermittent explosive disorder.

Intermittent explosive disorder (IED) is a psychiatric disorder characterized by repeated acts of affective aggression. Despite the diagnostic emphasis on the failure to control aggressive impulses, there is little research on affective processes and emotion regulation in IED; however, this research suggests possible dysfunctions in experiences of emotional intensity and lability. The hypothesis in the present study was that compared to individuals with other psychiatric disorders, and psychologically healthy individuals, individuals with IED experience greater negative affect intensity and emotional lability. Participants (N = 373) consisted of 202 individuals diagnosed with IED, 68 non-IED psychiatric controls (PC), and 103 healthy volunteers (HV). Emotion regulation was assessed using the General Behavior Inventory, the Affective Lability Scale, and the Affect Intensity Measure. Results showed that IED participants reported greater negative affect intensity and greater emotional lability across several emotion domains (e.g., anger, anxiety, depression) than PC and HV participants. These findings suggest that IED is characterized by more global emotion regulation deficits than those associated with anger alone. Aggr. Behav. 41:25-33 2015. © 2014 Wiley Periodicals, Inc.

Validity of the new A1 and A2 criteria for DSM-5 intermittent explosive disorder.

A disorder of impulsive aggression has been in the Diagnostic and Statistical Manual for Mental Disorders (DSM) since the first edition. In DSM-III, this disorder was codified as Intermittent Explosive Disorder (IED) and was thought to be rare. However, DSM criteria for IED were poorly operationalized and empiric research in IED was limited until the past decade when research criteria were developed. Subsequently, renewed interest in disorders of impulsive aggression led to a recent series of community based studies that have now documented IED to be as common as many other psychiatric disorders. Recent research indicates that the core of IED (A criteria) can be captured with new criteria that identify high frequency/low intensity aggressive outbursts (A1) and low frequency/hi intensity outbursts (A2). This paper presents new data regarding the phenomenology, comorbidity/life course of IED as a function of A1 and A2 criteria. Together with reanalysis of previously published data regarding family history, biomarkers, and treatment response in individuals with recurrent, problematic, impulsive aggression, these data provide empirical support for both A1 and A2 criteria for DSM-5 IED.