5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression

Abstract

The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or L G ) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.

Molecular epidemiology of major depressive disorder

“…However, the second study found that the SS genotype or S allele was nonsignificantly associated with decreased risk of depression in the British population [140]. A nonsignificant protective effect of the S allele was observed among Spaniards [109] and Germans [141,142]. Five studies of whites [143][144][145][146][147] found no substantial relationships between the 5-HTTLPR genotype and major depressive disorder.…”

Understanding vulnerability for depression from a cognitive neuroscience perspective: A reappraisal of attentional factors and a new conceptual framework

“…Interestingly, the serotonin system is related to emotion regulation, most likely through its effects on attentional control over negative stimuli; that is, many experimental studies show that 5-HT is implicated in enhanced sensitivity to negative stimuli and modulates the responsiveness of the amygdala via connected frontal regions (for reviews, see Cools, Roberts, & Robbins, 2007;Hariri & Holmes, 2006). Moreover, the amygdala response to negative stimuli is revealed to be associated with the above-mentioned polymorphism of 5-HT (e.g., Dannlowski et al, 2008). It has been proposed that the short allele variant, associated with a reduced 5-HT function, causes increased brain responses to negative stimuli (Bethea et al, 2004).…”

Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression

“…A replicated association has been found between amygdala reactivity to emotional stimuli and a polymorphism in the serotonin transporter gene (Hariri et al, 2002Pezawas et al, 2005), and other genes in the serotonergic pathway also seem to influence amygdala reactivity (Brown et al, 2005;Buckholtz et al, 2007;Dannlowski et al, 2007;Iidaka et al, 2005). tioning.…”