Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects

Abstract

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 (DeltaPRL[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. DeltaPRL[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. DeltaPRL[d-FEN]-R values were reduced in PD subjects with a history of suicidal behavior but not, self-injurious behavior. DeltaPRL[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.

Figure 1

Correlation between PRL[d-FEN]-R and composite aggression values in all PD and all HC subjects. Correlation in all subjects: r=−0.34, p<0.001; correlation in all PD subjects: r=−0.28, p=0.011; correlation in all HC subjects: r=−0.17, p=0.273.

Figure 2

Mean (±SEM) PRL[d-FEN]-R values in HC subjects (left) and in PD subjects without history of suicide attempt (middle; PD/SA−) and in PD subjects with history of suicide attempt (right; PD/SA+). ^*p<0.02 for PD/SA− vs HC, ^**p<0.05 for PD/SA+ vs PD/SA− and p<0.001 for PD/SA+ vs HC.

Figure 3

Mean (±SEM) PRL[d-FEN]-R values in PD subjects with and without IED by DSM-IV criteria (left), by IED-R criteria (middle), and by IED-IR criteria (right).