Outcome Following Antidepressant Treatment on Possible Endo-Phenotypes for Major Depression

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether outcome following antidepressant treatment can be used as a tool to evaluate endo-phenotypes for depression.

Detailed Description
-----------------
The research in depression has for some years focused at the identification of endo-phenotypes. Endo-phenotypes are heritable biological or psychological markers, which are more commonly found in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system as a possible endo-phenotype for depression. The hypothesis of AGENDA are that endo-phenotypes are affected by treatment with antidepressants in healthy first degree relatives. AGENDA is a four week randomized, placebo-controlled, double-blind trial in which first degree relatives of patients with the diagnosis of depression are randomised in to two groups, which are treated with either placebo or antidepressant medicine (Cipralex). We expect to include 80 healthy subjects, with the predisposition for depression, since one of their parents or siblings recently was treated for depression. The subjects will be examined before and after four weeks of treatment by a thorough interview concerning psychiatric symptoms (SCAN), including depressive symptoms, personality, perceived stress and cognitive function. The effect of antidepressant on stress is measured with saliva-cortisol and by the response to the combined dexamethasone corticotropin-releasing (CRH) hormone test. Additionally, MR and PET scans of the 5-HT4 receptor function will be conducted before and after 4 weeks of treatment.

Official Title
-----------------
Associations Between Gene-Polymorphisms, Endo-Phenotypes for Depression and Antidepressive Treatment (AGENDA)

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Escitalopram
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Offsprings or siblings of patients with major depression Born in Denmark with European parents and grandparents For women; not pregnant or breastfeeding Written informed consent Exclusion Criteria: Somatically illness or other handicaps which make participation in the study impossible Daily intake of drugs interfering with corticosteroids or escitalopram Hypersensitivity to escitalopram, dexamethasone or human corticotropin-releasing hormone Former medical or psychological treatment for diseases in the affective or schizophrenic spectrum Ongoing addiction of alcohol or psychoactive drugs

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A Escitalopram 10 mg<br>Escitalopram 10 mg | Drug: Escitalopram<br>* Escitalopram 10 mg p.o. per day<br>* Other names: cipralex;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the response on the combined dexamethasone corticotropin-releasing hormone test before and after 4 weeks treatment with escitalopram or placebo. |  | 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in scores before and after 4 weeks treatment with escitalopram or placebo on: Cognition |  | 4-6 weeks | 
| Social function |  | 4-6 weeks | 
| Neuroticism |  | 4-6 weeks | 
| Subjective; sleep, pain, aggression, depression, anxiety, quality of life, perceived stress and side-effects |  | 4-6 weeks | 
| Receptor status by PET-scans |  | 4-6 weeks | 
| Inflammatory parameters |  | 4-6 weeks | 
| Paraclinical measures |  | 4-6 weeks | 
| MR and fMRI |  | 4-6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major depression, First degree relatives, Escitalopram, Cortisol, Cognition, Personality, Endo-phenotype