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

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.

Conditions

• Major Depression

Interventions

DRUG

SSRI; SNRI; TCA

Tablets or Pills, 1 or 2 per day, more than 2 month

Sponsors & Collaborators

• University of Michigan

  collaborator OTHER

• Ariel University

  collaborator OTHER

• The Nazareth Hospital, Israel

  collaborator OTHER

• Tirat Carmel Mental Health Center

  lead OTHER_GOV

Principal Investigators

• Anatoly Kreinin, MD, PhD · The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa

• Albert Pinhasov, PhD · Department of Molecular Biology at Ariel University Center

• Leon Raskin, PhD · University of Michigan

• Kamal Farhat, MD · The Nazareth Hospital-EMMS

• Joseph Farah, MD · The Nazareth Hospital-EMMS

• Klaudia Rybalksy, MD · The Nazareth Hospital-EMMS

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-06-30

Primary Completion

2010-06-30

Completion

2012-07-31

Countries

• Israel