Startle Latency as a Potential Marker for Amygdala-Mediated Hyperarousal

BACKGROUND: Fear-related disorders are characterized by hyperexcitability in reflexive circuits and maladaptive associative learning mechanisms. The startle reflex is suited to investigate both processes, either by probing it under baseline conditions or by deriving it in fear conditioning studies. In anxiety research, the amplitude of the fear-potentiated startle has been shown to be influenced by amygdalar circuits and has typically been the readout of interest. In schizophrenia research, prolonged startle peak latency under neutral conditions is an established readout, thought to reflect impaired processing speed. We therefore explored whether startle latency is an informative readout for human anxiety research.METHODS: We investigated potential similarities and differences of startle peak latency and amplitude derived from a classical fear conditioning task in a sample of 206 participants with varying severity levels of anxiety disorders and healthy control subjects. We first reduced startle response to stable components and regressed individual amygdala gray matter volumes onto the resulting startle measures. We then probed time, stimulus, and group effects of startle latency.RESULTS: We showed that startle latency and startle amplitude were 2 largely uncorrelated measures; startle latency, but not amplitude, showed a sex-specific association with gray matter volume of the amygdala; startle latencies showed a fear-dependent task modulation; and patients with fear-related disorders displayed shorter startle latencies throughout the fear learning task.CONCLUSIONS: These data provide support for the notion that probing startle latencies under threat may engage amygdala-modulated threat processing, making them a complementary marker for human anxiety research.