Genetic variation in serotonin transporter function affects human fear expression indexed by fear-potentiated startle

The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N = 82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation.

► We examined how 5-HTT genetics bias fear up- and downregulation.
► 5-HTTLPR S-carriers showed greater fear-potentiated startle than L/L homozygotes.
► In rest periods after threat, fear diminished to similar levels across genotypes.
► 5-HTTLPR genetic variance may thus affect fear intensity but not the capacity to reduce fear.