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Study suggests strategy to ease stress-related anxiety and alcohol use

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COLUMBUS, Ohio — Clinicians and researchers have known for some time that uncertainty fuels anticipatory anxiety — that heightened sense of caution and alertness when danger lurks. Although uncertainty is universally unpleasant, some people are particularly sensitive to uncertain threats in their environment. This sensitivity can manifest as chronic anticipatory anxiety and, for some, excessive alcohol abuse.

“There are now drugs to treat anxiety and alcohol use disorders, but they are only modestly effective and don’t work for everyone,” said lead author Stephanie M. Gorka, associate professor in psychiatry and behavioral health and a researcher specializing in anxiety and addiction. troubles. “There is an urgent need for new, more effective drug therapies for these often-related conditions,” she added.

This study was designed to show whether antagonism of the human orexin system reduced objective markers of anticipatory anxiety in the laboratory. Suvorexant, an FDA-approved drug for the treatment of insomnia, has been used to manipulate the orexin system in human volunteers. Orexins are small molecules, or peptides, which are produced in the hypothalamus and regulate a range of processes such as wakefulness, arousal, energy metabolism and stress responses.
“Our results suggest that a single dose of an antagonist of the orexin system alleviates anticipatory anxiety,” said lead researcher Dr. K. Luan Phan, professor and chair of the Department of Psychiatry and Behavioral Health at Ohio State. “The results are particularly important because they suggest that the orexin system is a promising target for the development of next-generation drugs.”

The proof-of-concept study involved 21 healthy volunteers who received either the drug or an identical-looking sugar placebo. Two hours after receiving the tablets, the volunteers were given a lab task designed to induce anticipatory anxiety using the threat of a mild electric shock to the wrist.

The test included three conditions: anticipation of a predictable shock, anticipation of an unpredictable shock and no shock. A computer screen displayed text telling the volunteer what condition he was in. The amplitude or strength of the human startle reflex was recorded under each of the three conditions. Blinking is a well-validated marker of current anxiety levels in humans and animals.

A digital countdown timer was used to manipulate the predictability of the electric shock. During the predictable shock condition, participants were informed that a shock would be delivered each time the countdown reached “1”. During the unpredictable shock condition, shocks were delivered randomly so that the timing was uncertain, leading to increased anticipatory anxiety. No shock was delivered during the no-shock condition.

In addition to measuring eye blinking during the task, the researchers used questionnaires to assess subjective drug effects and participants’ mood states during the study.

“Although preliminary,” Gorka said, “our results suggest that orexin antagonism strongly attenuates anticipatory anxiety in response to uncertainty. This could be a promising strategy for treating anxiety disorders and possibly stress-related alcohol consumption Further research is warranted and our lab plans to continue this important line of work.

The collaborators on this Ohio State study were Kia J. Khorrami and Charles A. Mangler.

The study was funded by the Ohio State University Department of Psychiatry and Behavioral Health.

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Written by Darrell Ward, [email protected]

Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, [email protected]