Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter

Abstract

Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…Human fMRI studies indicate replicable association between the 5-HTTLPR s allele and greater reactivity to negative emotional compared to neutral stimuli in the amygdale. [95][96][97][98] This association is independent of gender and the temperamental trait of harm avoidance. 96 Furthermore, the 'functional connectivity' (correlation of activity) of the amygdala to the ventromedial prefrontal cortex was stronger 98 and the connectivity to the perigenual anterior cingulate was weaker 99 in the s allele carriers compared to ll homozygotes.…”

“…[95][96][97][98] This association is independent of gender and the temperamental trait of harm avoidance. 96 Furthermore, the 'functional connectivity' (correlation of activity) of the amygdala to the ventromedial prefrontal cortex was stronger 98 and the connectivity to the perigenual anterior cingulate was weaker 99 in the s allele carriers compared to ll homozygotes. 98,99 The relative 'uncoupling' of amygdala from the anterior cingulate in the s allele carriers correlated with a measure of harm avoidance, suggesting that strong amygdala activity free from anterior cingulate control may be responsible for anxiety-related traits associated with the 5-HTTLPR.…”

“…96 Furthermore, the 'functional connectivity' (correlation of activity) of the amygdala to the ventromedial prefrontal cortex was stronger 98 and the connectivity to the perigenual anterior cingulate was weaker 99 in the s allele carriers compared to ll homozygotes. 98,99 The relative 'uncoupling' of amygdala from the anterior cingulate in the s allele carriers correlated with a measure of harm avoidance, suggesting that strong amygdala activity free from anterior cingulate control may be responsible for anxiety-related traits associated with the 5-HTTLPR. 99 Studies that include a passive baseline (fixation cross) show that the apparent over-reactivity to negative stimuli is largely explained by decreased reactivity of the amygdala to neutral stimuli compared to the passive baseline.…”

“…106 In contrast, human functional neuroimaging studies suggest functionally dominant s allele. 96,98 The human G Â E studies provide an inconsistent picture. In the original investigation by Caspi and colleagues, 11 the data pattern is clearly indicative of a co-dominant effect with the s/l heterozygotes falling intermediate in all analyses and similar pattern was reported in several other studies.…”

The role of learning-related dopamine signals in addiction vulnerability

“…This downregulation may be a consequence of drug-taking, but it may also predispose to the development of addiction and to relapse (Volkow et al, 2009;Morgan et al, 2002;Thanos et al, 2001;Heinz et al, 2005;Volkow et al, 2002;Buckholtz et al, 2010). Dopamine D 2 receptors are both pre-and postsynaptically located.…”