Abstract
Background and AimsThe 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus.MethodsTwenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).ResultsDuring baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.ConclusionIn male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.
Highlights
The serotonin (5-hydroxytryptamine; 5-HT) signaling system plays an important role in modulating a wide range of brain functions [1], including brain networks involved in emotion regulation, stress response and processing of interoceptive signals [2]
Subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual anterior cingulate cortex (ACC) on amygdala activity compared to l-carriers
Subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers
Summary
The serotonin (5-hydroxytryptamine; 5-HT) signaling system plays an important role in modulating a wide range of brain functions [1], including brain networks involved in emotion regulation, stress response and processing of interoceptive signals [2]. Reduced expression of 5-HTT results in a higher synaptic 5-HT concentration and down regulation of pre- and post-synaptic 5-HT receptors [6]. Such alterations in the serotonergic synapse may acutely alter the response of the brain to certain stimuli, or it may affect the role of 5-HT during brain development [7] or both. Such changes in 5-HT signaling have been implicated in the increased susceptibility to negative mood states, and increased stress responsiveness in individuals with the s allele. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus
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