Functional Brain Imaging of Impulsive Aggression

Abstract

Impulsive aggressive behaviour, including deliberate self-harm and impulsive aggression towards others as well as suicidal behaviour, constitute a major problem in mental health care. Primate and human research on anatomical brain lesions and epileptic activity has pointed to prefrontal and temporal limbic regions as the neuroanatomical regions involved in impulsive aggressive behaviour and suicidal behaviour. Indirect measurements of the neurotransmitter serotonin found diminished functioning of the serotonin system, supposed to be the neurochemical underpinning of impulsive aggressive behaviour and suicidal behaviour. Although studies on post-mortem tissue, peripheral body fluids and serotonergic challenge studies have been conducted, the specific nature of the serotonergic dysfunction remains unclear. PET and SPECT techniques visualize brain metabolism and perfusion patterns in the living human brain and therefore contribute substantially to exploring neural circuits of anger/aggression as normal emotions in healthy human and impulsive aggression in psychiatric patients. The ventral and medial part of the prefrontal cortex appeared to be hypo-activated in association with aggressive and/or suicidal behaviour, while abnormal activity was reported in limbic regions. Novel applications of the PET and SPECT techniques enable assessment of specific aspects of the serotonergic transmission, including the responsivity of brain metabolism to serotonin challenge. Compared to normal controls, blunted responses to a serotonergic stimulus are found in regions comparable to the hypo-activated areas in baseline perfusion/metabolism studies, which implies serotonergic modulation of these regions. Findings from imaging studies that investigate serotonin receptor systems, the serotonin transporter and markers of serotonin synthesis, suggest diminished serotonin synthesis, lower serotonin reuptake sites and a reduced binding index of some postsynaptic receptor subtypes in impulsive aggressive and/or suicidal behaviour. Functional neuro-imaging techniques have proven to be useful tools to elucidate the neurobiological underpinnings of impulsive aggressive and suicidal behaviour. Study results support the hypothesis that impulsive aggression and suicidal behaviour share a common underlying predisposition. Unfortunately, the lack of consensus in defining impulsive aggression and methodological issues have complicated interpretations, and hence conclusions. Integrating these biological findings with personality-related, cognitive and emotional correlates of impulsive aggressive and suicidal behaviour can be expected to increase the insight into the pathophysiology of impulsive aggression. This may lead to the development of much needed new approaches to the prevention and management of aggression and suicidal behaviour.