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

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.

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