Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression

Study Overview
=================
Brief Summary
-----------------
The neuropeptide Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and its receptors PAC1 and VPAC2 are widely expressed in the nervous system. The investigators found that PACAP treatment of neuronal cell cultures increases expression of Brain Derived Neurotrophic Factor (BDNF) that plays an important role in the etiology of psychiatric disorders and action of antidepressants. For the first time, the investigators demonstrated that treatment by Paroxetine and Citalopram significantly decreases PAC1 and VPAC2 and upregulates PACAP mRNA expression, whereas Imipramine shows an opposite effect. Moreover, PACAP, PAC1 and VPAC2 expression is highly correlated with BDNF expression. Their in vivo studies show that Imipramine reduces BDNF and increases PAC1 mRNA expression in murine hippocampus, suggesting that antidepressants may affect neuronal plasticity through PACAP-BDNF interactions. Based on their observations in experimental systems, the investigators hypothesize that PACAP signaling system may be involved in the etiology of depression and mechanism of antidepressant action. The investigators will evaluate this hypothesis by examining serum PACAP levels, effect of antidepressants on PACAP levels, and gene polymorphisms of PACAP and its receptors in major depressive disorder patients. This study will enhance the investigators' understanding of PACAP's role in the etiology of depression and antidepressant treatment and will provide a basis to evaluate PACAP pathway as a potential target for diagnostics and novel antidepressants drug discovery.

Official Title
-----------------
Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression

Conditions
-----------------
Major Depression

Intervention / Treatment
-----------------
* Drug: SSRI; SNRI; TCA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women 18-65 age old Patients with DSM-IV (or/and ICD-10) diagnosis MDD Volunteers without DSM-IV (or/and ICD-10) diagnosis MDD For patients with DSM-IV (or/and ICD-10) diagnosis MDD minimum 2 weeks free from benzodiazepines, mood stabilizers and neuroleptics. All patients from MDD group treatment only by SSRI antidepressant medications. Exclusion Criteria: MDD with Co-morbidity Alcohol and drug use less than 1 month before the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: antidepressant<br> | Drug: SSRI; SNRI; TCA<br>* Tablets or Pills, 1 or 2 per day, more than 2 month<br>* Other names: anafranil;|
| No Intervention: Healthy volunteers<br> | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurements of PACAP and BDNF serum levels |  | Blood samples will be collected at the study base line, two and three weeks after that and at the study end point (8 weeks after study initiation) | 
| Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions |  | Blood samples will be collected at the study base line, two and three weeks after that and at the study end point (8 weeks after study initiation) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Receptors, PACAP (Pituitary Adenylate Cyclase Activating Polypeptide), Major Depression, Gene polymorphism, PACAP signaling system, Etiology of major depression, Mechanism of antidepressants action, PACAP receptors gene polymorphism, Pathogenesis of major depression, Responsiveness to the antidepressant drugs