Amygdala functions and reactivity have been identified to play a major role in mood disorders and anxiety. A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. There is converging evidence that SCL6A4 genotype accounts for about 30% of the total variance in amygdala response during the presentation of aversive but not affectively positive visual stimuli, which were equally salient. S-allele carriers also showed stronger prefrontal-amygdala connectivity. This suggests that increased amygdala responses in s-allele carriers are related to altered serotonergic modulation of prefrontal afferents within the amygdala. In patients with major depression amygdala activation to aversive stimuli and prefrontal connectivity may be dysfunctional. This hypothesis was tested in 20 patients with major depression and 20 age-matched healthy controls.

Results will be discussed with respect to genotype effects on limbic activation and connectivity.