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

The Role of Stress Neuromodulators in Decision Making Under Risk

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.

Study Overview

• Status: Completed
• Conditions: Placebo; Hydrocortisone; Yohimbine; Yohimbine + Hydrocortisone
• Intervention / Treatment: Drug: "Yohimbine"; Drug: "Hydrocortisone"; Drug: "Yohimbine + Hydrocortisone"; Drug: "Placebo"

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Charité University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: "Placebo"; Effects on neural correlates of decision-making under risk and selective attention to threat; Other Names: Pill (oral administration)
Active Comparator: Yohimbine; 10 mg	Drug: "Yohimbine"; Effects on neural correlates of decision-making under risk and selective attention to threat; Other Names: Pill (oral administration)
Active Comparator: Hydrocortisone; 10 mg	Drug: "Hydrocortisone"; Effects on neural correlates of decision-making under risk and selective attention to threat; Other Names: Pill (oral administration)
Active Comparator: Yohimbine + Hydrocortisone; 10 mg each	Drug: "Yohimbine + Hydrocortisone"; Effects on neural correlates of decision-making under risk and selective attention to threat; Other Names: Pill (oral administration)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary cortisol	Treatment check	3 hours
Salivary alpha amylase	Treatment check	3 hours
Systolic and diastolic blood pressure	Treatment check	3 hours
Heart rate	Treatment check	3 hours

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): December 22, 2021
• Study Completion (Actual): December 22, 2021

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Urological Agents; Anti-Inflammatory Agents; Adrenergic alpha-Antagonists; Mydriatics; Adrenergic alpha-2 Receptor Antagonists; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Yohimbine
• Other Study ID Numbers: WI-3396-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No