Noradrenergic Activity, Cognition and Major Depressive Disorder

Study Overview
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Brief Summary
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This study investigates influences of nordadrenergic activity on cognition in patients with major depression regarding influences of early life stress.

Detailed Description
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Stress plays a major role in the development and maintenance of major depression disorder. Indeed, various studies demonstrated maladaptive changes in physiological stress regulation systems of depressive patients, i.e. in the hypothalamus-pituitary-adrenal axis and the locus coeruleus-noradrenergic system. On a central level, changes of the locus coeruleus-noradrenergic system have been demonstrated.This seems to be the case especially in depressive patients with early life traumata. Comparable to the hypothalamus-pituitary-adrenal axis, the locus coeruleus-noradrenergic system influences not only the physiological stress response, but has also central influence with effects on cognitive functions. Indeed, noradrenergic effects on cognitive functions such as attention, learning and memory have been demonstrated in healthy individuals. Even though deficits in cognitive domains are core symptoms of major depression, the relationship of the noradrenergic system and cognitive processes has rarely been investigated so far. In this project, the investigators will examine noradrenergic influences via administration of the alpha2-receptor blocker yohimbine on cognitive and emotionally relevant processes in depressive patients and controls. Additionally, the investigators will examine the influence of early life traumata on these relationships. Thus, the investigators will examine participants with and without major depression and with and without early life stress. Results of this study will improve the understanding of cognitive dysfunctions associated with the noradrenergic system in patients with major depression.

Official Title
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Influences on Noradrenergic Activity for Cognition in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder, Early Life Trauma

Intervention / Treatment
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* Drug: yohimbine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of major depression experience of early life trauma Exclusion Criteria: severe illness Alzheimer´s schizophrenia bipolar disorder control group: - diagnosis of major depression/ experience of early life trauma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yohimbine-Placebo<br>single low dose treatment with yohimbine on test day 1, placebo on test day 2 | Drug: yohimbine<br>* single low dose treatment<br>Drug: placebo<br>* single control treatment<br>|
| Experimental: Placebo-Yohimbin<br>placebo on test day 1, single low dose treatment with yohimbine on test day 2 | Drug: yohimbine<br>* single low dose treatment<br>Drug: placebo<br>* single control treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| behavioral responses in two different conditions of noradrenergic stimulation | reaction times and error scores (computer tasks) | 2,5 hrs | 
| physiological responses in two different conditions of noradrenergic stimulation | physiological recordings, saliva samples | 2,5 hrs |