1. ¹Personality and Individual Differences, Institute of Psychology II, Dresden University of Technology, Dresden, Germany
2. ²Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
3. ³Institute of Psychology I, Dresden University of Technology, Dresden, Germany

Correspondence: Dr B Brocke, Personality and Individual Differences, Institute of Psychology II, Dresden University of Technology, Dresden 01062, Germany. E-mail: brocke@rcs.urz.tu-dresden.de

Received 6 January 2006; Revised 31 August 2006; Accepted 1 September 2006; Published online 10 October 2006.

Abstract

Anxiety-related behaviors are closely linked to neural circuits relaying fear-specific information to the amygdala. Many of these circuits, like those underlying processing of innate fear, are remarkably well understood. Recent imaging studies have contributed to this knowledge by discriminating more detailed corticoamygdalar associations mediating processing fear and anxiety. However, little is known about the underlying molecular mechanisms. We used the acoustic startle paradigm to investigate the impact of molecular genetic variation of serotonergic function on the acoustic startle response and its fear potentiation. Startle magnitudes to noise bursts as measured with the eye blink response were recorded in 66 healthy volunteers under four conditions: presenting unpleasant and pleasant affective pictures as well as neutral pictures, and presenting the startle stimulus without additional stimuli as a baseline. Subjects were genotyped for functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-hydroxytryptamine transporter gene-linked region: 5-HTTLPR). Analyses of variance revealed a significant effect of 5-HTTLPR on overall startle responses across conditions. Carriers of the short (s) allele exhibited stronger startle responses than l/l homozygotes. However, we could not confirm our hypothesis of enhanced fear potentiation of the startle in s allele carriers. In conclusion, the results provide first evidence that the startle response is sensitive to genetic variation in the serotonin pathway. Despite some issues remaining to be resolved, the startle paradigm may provide a valuable endophenotype of fear processing and underlying serotonergic influences.