Serotonin Transporter Availability in the Amygdala and Bed Nucleus of the Stria Terminalis Predicts Anxious Temperament and Brain Glucose Metabolic Activity

Abstract

The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.