The Prevalence and Correlates of DSM-IV Intermittent Explosive Disorder in the National Comorbidity Survey Replication

Central serotonergic (5-HT) activity has long been implicated in the regulation of impulsive aggressive behavior. This study was performed to use a highly selective agent for 5-HT (d-Fenfluramine, d-FEN) in a large group of human subjects to further explore this relationship dimensionally and categorically. One hundred and fifty healthy subjects (100 with personality disorder, PD and 50 healthy volunteer controls, HV) underwent d-FEN challenge studies. Residual peak delta prolactin (DPRL[d-FEN]-R; ie, after the removal of potentially confounding variables) was used as the primary 5-HT response variable. Composite measures of aggression and impulsivity were used as dimensional measures, and history of suicidal/self-injurious behavior as well as the presence of intermittent explosive disorder (IED) were used as categorical variables. DPRL[d-FEN]-R responses correlated inversely with composite aggression, but not composite impulsivity, in all subjects and in males and females examined separately. The correlation with composite aggression was strongest in male PD subjects. DPRL [d-FEN]-R values were reduced in PD subjects with a history of suicidal behavior but not, selfinjurious behavior. DPRL [d-FEN]-R values were also reduced in patients meeting Research Criteria for IED. Physiologic responses to 5-HT stimulation are reduced as a function of aggression (but not generalized impulsivity) in human subjects. The same is true for personality disordered subjects with a history of suicidal, but not self-injurious, behavior and for subjects with a diagnosis of IED by research criteria. These data have particular relevance to the notion of impulsive aggression and the biological validity of IED.

The revision effort leading to the publication of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was flawed in process, goals and outcome. The revision process suffered from lack of an adequate public record of the rationale for changes, thus shortchanging future scholarship. The goals, such as dimensionalising diagnosis, incorporating biomarkers and separating impairment from diagnosis, were ill-considered and mostly abandoned. However, DSM-5's greatest problem, and the target of the most vigorous and sustained criticism, was its failure to take seriously the false positives problem. By expanding diagnosis beyond plausible boundaries in ways inconsistent with DSM-5's own definition of disorder, DSM-5 threatened the validity of psychiatric research, including especially psychiatric epidemiology. I present four examples: increasing the symptom options while decreasing the diagnostic threshold for substance use disorder, elimination of the bereavement exclusion from major depression, allowing verbal arguments as evidence of intermittent explosive disorder and expanding attention-deficit/hyperactivity disorder to adults before addressing its manifest false positives problems.

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short-and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions.