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

Charité University Medicine Berlin

Status: Completed

Conditions: Hydrocortisone; Yohimbine; Yohimbine + Hydrocortisone; Placebo

Treatments: Drug: "Yohimbine"; Drug: "Placebo"; Drug: "Yohimbine + Hydrocortisone"; Drug: "Hydrocortisone"

Study type: Interventional

Funder types: Other

Identifiers

NCT04359147

WI-3396-3

Details and patient eligibility

About

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.

Enrollment: 167 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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167 participants in 4 patient groups, including a placebo group

Yohimbine

Active Comparator group

Description:

10 mg

Treatment:

Drug: "Yohimbine"

Hydrocortisone

Active Comparator group

Description:

10 mg

Treatment:

Drug: "Hydrocortisone"

Yohimbine + Hydrocortisone

Active Comparator group

Description:

10 mg each

Treatment:

Drug: "Yohimbine + Hydrocortisone"

Placebo

Placebo Comparator group

Treatment:

Drug: "Placebo"