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

Not Applicable

Completed

• Conditions: Yohimbine; Hydrocortisone; Yohimbine + Hydrocortisone; Placebo
• Interventions: Drug: "Hydrocortisone"; Drug: "Yohimbine"; Drug: "Yohimbine + Hydrocortisone"; Drug: "Placebo"

• Registration Number: NCT04359147
• Lead Sponsor: Charite University, Berlin, Germany

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-01
• Study First Submitted: 2020-04-20
• Study First Submitted QC: 2020-04-22
• Study First Posted: 2020-04-24
• Primary Completion: 2021-12-22
• Study Completion: 2021-12-22
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-14
• Last Update Posted: 2022-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 167

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydrocortisone	"Hydrocortisone"	10 mg
Yohimbine	"Yohimbine"	10 mg
Yohimbine + Hydrocortisone	"Yohimbine + Hydrocortisone"	10 mg each
Placebo	"Placebo"	-

Primary Outcome Measures

Name	Time	Method
Attentional bias to fearful faces	12 minutes	Behavioural outcome of the dot-probe task
Risk and loss-aversion, choice consistency	45 minutes	Behavioural outcome of the decision-making under risk task modeled using prospect theory (PT)
Patch-leaving times	45 minutes	Behavioural outcome of the decision-making under risk task including a foraging task part using marginal value theory
Blood-oxygen-level-dependent (BOLD) response	45 + 12 minutes	In both tasks

Secondary Outcome Measures

Name	Time	Method
Salivary alpha amylase	3 hours	Treatment check
Systolic and diastolic blood pressure	3 hours	Treatment check
Heart rate	3 hours	Treatment check
Salivary cortisol	3 hours	Treatment check

Trial Locations

Locations (1)

Charite University; 🇩🇪 Berlin, Germany