Growth hormone responses to GABAB receptor challenge with baclofen and impulsivity in healthy control and personality disorder subjects

Abstract

The role of abnormal GABAergic neural transmission in impulsive aggression is not well understood. We have previously shown that central levels of GABA are positively correlated with impulsivity in adult humans with and without personality disorder. An important regulator of GABAergic function is the GABA(B) receptor, a presynaptic autoreceptor and heteroreceptor. GABA(B) receptor sensitivity may be tested by measuring the growth hormone response to the receptor-agonist baclofen. The purpose of this investigation is to test the hypothesis that dimensional measures of impulsivity and impulsive aggression are negatively correlated with growth hormone response. Twenty healthy volunteers (without Axis I or II disorder) and 20 personality-disordered subjects (meeting DSM-IV general criteria for personality disorder) underwent challenge with 20 mg baclofen administered orally, followed by a time series of blood samples for measure of growth hormone response analyzed by repeated measures ANOVA. An expected significant effect for drug and drug × time interaction verified that baclofen caused a surge in growth hormone level. There was no effect of group (healthy volunteer or personality disorder) or interaction with group on the time series or peak growth hormone response. As hypothesized, peak growth hormone response was negatively correlated with impulsivity as measured by the Barratt Impulsivity Scale (BIS-11; r = -0.39, n = 37, p < 0.02). The relationship remained significant when examining the healthy volunteer and personality disorder groups separately, indicating that the relationship with impulsivity was not merely due to the presence or absence of personality disorder. The relationship with impulsive aggression was only at a trend level of significance. The magnitude of growth hormone response to baclofen, an index of GABA(B) receptor function, was negatively correlated with a dimensional measure impulsivity, but not related to the categorical diagnosis of personality disorder. Further work is necessary to understand how GABAergic dysfunction may play a role in impulsive aggression.