Clinical trial NCT00944996: Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression
Official title: Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depression
Keywords: PACAP (Pituitary Adenylate Cyclase Activating Polypeptide)
Major Depression
Receptors
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
Lead sponsor: Tirat Carmel Mental Health Center
Sponsor class: OTHER_GOV
Collaborators: name: University of Michigan
name: Ariel University
name: The Nazareth Hospital, Israel
First posted: 2009-07-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. Men and women 18-65 age old
2. Patients with DSM-IV (or/and ICD-10) diagnosis MDD
3. Volunteers without DSM-IV (or/and ICD-10) diagnosis MDD
4. For patients with DSM-IV (or/and ICD-10) diagnosis MDD minimum 2 weeks free from benzodiazepines, mood stabilizers and neuroleptics.
5. All patients from MDD group treatment only by SSRI antidepressant medications.

Exclusion Criteria:

1. MDD with Co-morbidity
2. Alcohol and drug use less than 1 month before the study

Primary outcomes:
measure: Measurements of PACAP and BDNF serum levels
timeFrame: 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)
measure: Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Tirat Hacarmel
country: Israel
facility: Tirat Carmel Mental Health Center
Study officials:
affiliation: The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa
name: Anatoly Kreinin, MD, PhD
role: STUDY_CHAIR
affiliation: Department of Molecular Biology at Ariel University Center
name: Albert Pinhasov, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Leon Raskin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Nazareth Hospital-EMMS
name: Kamal Farhat, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Nazareth Hospital-EMMS
name: Joseph Farah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Nazareth Hospital-EMMS
name: Klaudia Rybalksy, MD
role: PRINCIPAL_INVESTIGATOR
References: