The Role of Stress Neuromodulators in Decision Making Under Risk and Selective Attention to Threat

NCT ID: NCT04359147

Last Updated: 2022-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2021-12-22

Brief Summary

Incidental affective states, i.e., affective states can influence decision making and selective attention to threatening information. Acute stress is such an affective state and is a powerful contextual modulator of decision-making processes and selective attention to threat. In terms of physiological and neurohormonal changes, the stress response has been well characterized: Exposure to stress elicits an array of autonomic, endocrine, and behavioral responses. The physiological stress response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus noradrenergic (LC-NA) system with cortisol and norepinephrine (NE) as their end products. There is compelling evidence that the stress hormones cortisol and NE influence cognitive processes. However, only very few studies so far used pharmacological approaches to specify the role of stress neuromodulators on decision making and selective attention to threat and these studies are hardly comparable due to differences in the experimental design, e.g., the decision making task used. Furthermore, the neural underpinnings of stress effects on decision making and selective attention to threat are uninvestigated so far. The aim of the proposed project is to clarify the role of the major stress neuromodulators, NE and cortisol, in their contribution to different processes related to decision making under risk and selective attention to threat. To this end, combined precise pharmacological stimulation, behavioral modeling, and fMRI methods will be applied to systematically disentangle the effects of stress hormones on risk attitudes and loss aversion as well as their relation to neural correlates of processing subjective value and risk. Using pharmacological manipulation, the influence of noradrenergic and glucocorticoid activity on decision making under risk at the behavioral, computational, and neural level will be investigated. In addition, the influence of noradrenergic and glucocorticoid activity on selective attention to threat at the behavioural and neural level using a dot-probe paradigm with fearful and neutral faces will be examined. Participants are randomly assigned to one of four groups: (A) yohimbine, (B) hydrocortisone, (C) yohimbine and hydrocortisone, or (D) placebo.

Conditions

Yohimbine; Hydrocortisone; Yohimbine + Hydrocortisone; Placebo

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Yohimbine

10 mg

Group Type: ACTIVE_COMPARATOR

"Yohimbine"

Intervention Type: DRUG

Effects on neural correlates of decision-making under risk and selective attention to threat

Hydrocortisone

10 mg

Group Type: ACTIVE_COMPARATOR

"Hydrocortisone"

Intervention Type: DRUG

Effects on neural correlates of decision-making under risk and selective attention to threat

Yohimbine + Hydrocortisone

10 mg each

Group Type: ACTIVE_COMPARATOR

"Yohimbine + Hydrocortisone"

Intervention Type: DRUG

Effects on neural correlates of decision-making under risk and selective attention to threat

Placebo

Group Type: PLACEBO_COMPARATOR

"Placebo"

Intervention Type: DRUG

Effects on neural correlates of decision-making under risk and selective attention to threat

Interventions

"Yohimbine"

Effects on neural correlates of decision-making under risk and selective attention to threat

Intervention Type: DRUG

"Hydrocortisone"

Effects on neural correlates of decision-making under risk and selective attention to threat

Intervention Type: DRUG

"Yohimbine + Hydrocortisone"

Effects on neural correlates of decision-making under risk and selective attention to threat

Intervention Type: DRUG

"Placebo"

Effects on neural correlates of decision-making under risk and selective attention to threat

Intervention Type: DRUG

Other Intervention Names

Pill (oral administration); Pill (oral administration); Pill (oral administration); Pill (oral administration)

Eligibility Criteria

Inclusion Criteria

• Right-handed
• High-school diploma

Exclusion Criteria

• Former and present DSM-5 axis I disorders according to the Structured Clinical Interview for DSM (SCID)
• Permanent medication of any kind
• Medical conditions associated with adrenal dysfunction or well-known impact on HPA activity or cognitive function
• Steroid use

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Katja Wingenfeld

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Charite University

Berlin, , Germany

Countries

Germany

References

Rosada C, Lipka R, Metz S, Otte C, Heekeren H, Wingenfeld K. Effects of stress-related neuromodulators on amygdala and hippocampus resting state functional connectivity. J Psychopharmacol. 2024 Jul;38(7):604-614. doi: 10.1177/02698811241260972. Epub 2024 Jun 20.

Reference Type: DERIVED

PMID: 38902928 (View on PubMed)

Other Identifiers

WI-3396-3

Identifier Type: -

Identifier Source: org_study_id