Neuroimaging findings in major depression, suicidal behavior and aggression

Abstract

Studies of the neurobiology of suicidal behavior have focused on serotonergic abnormalities. We will review neuroimaging studies of major depression since the few studies of suicidal behavior were conducted in this population. Because of the relationship between suicidal behavior, aggression and serotonergic dysfunction, studies of aggression also will be reviewed. Magnetic resonance imaging (MRI) studies suggest that frontal lobe volume is reduced in major depressives. Major depression appears to be associated with hyperperfusion of the amygdala, orbital cortex, medial thalamus, ventrolateral PFC, subgenual cortex and anterior insula and decreased perfusion in other PFC areas and the striatum. Metabolic changes in cortical regions have been correlated with symptom severity or treatment resistance. In one study, depressed subjects, two of whom were suicide attempters, showed a blunted metabolic response to fenfluramine compared to normal controls. A similar study of depressed women with no suicidal behavior using PET to assess changes in CBF after intravenous d-fenfluramine, found no differences in response compared to healthy volunteers. Lower serotonin transporter receptor binding potential (BP) is associated with major depression. Depressed subjects also have lower 5HT 1A BP in the raphe nucleus and in the mesiotemporal cortex (amygdala and hippocampus together). Some, but not all studies show that depressed subjects have lower 5-HT 2A BP in frontal, temporal and parietal cortex. Changes in 5-HT 2A receptor BP may be related to suicidal behavior rather than depression. A comparison of high lethality and low lethality suicide attempters with major depression showed that the high lethality attempters appeared to had a relative hypofunction in prefrontal cortex compared to depressed low lethality attempters. That difference became more extensive after fenfluramine administration. Aggressive individuals appear to have an abnormality in PFC regardless of their psychiatric condition. In addition, two studies suggest that serotonergic functioning is decreased in aggressive individuals with psychiatric conditions. Thus, the PFC may regulate aggressive behavior by inhibition of impulsive urges. Although, more studies are needed to investigate in vivo the pathophysiology of suicidal behavior, there is evidence of involvement of the PFC, consistent with postmortern brain findings. Clinical descriptions of samples of subjects in neuroimaging studies should include details regarding suicidal behavior, depression and aggression to determine the relationships of psychopathology to regional of brain functions or structures.