Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression
Information source: Tirat Carmel Mental Health Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depression
Intervention: SSRI; SNRI; TCA (Drug)
Phase: N/A
Status: Completed
Sponsored by: Tirat Carmel Mental Health Center Official(s) and/or principal investigator(s): Anatoly Kreinin, MD, PhD, Study Chair, Affiliation: The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa Albert Pinhasov, PhD, Principal Investigator, Affiliation: Department of Molecular Biology at Ariel University Center Leon Raskin, PhD, Principal Investigator, Affiliation: University of Michigan Kamal Farhat, MD, Principal Investigator, Affiliation: The Nazareth Hospital-EMMS Joseph Farah, MD, Principal Investigator, Affiliation: The Nazareth Hospital-EMMS Klaudia Rybalksy, MD, Principal Investigator, Affiliation: The Nazareth Hospital-EMMS
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.
Clinical Details
Official title: Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression
Study design: Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Primary outcome: Measurements of PACAP and BDNF serum levelsAnalysis of genetic variants of PACAP and PAC1 coding and regulatory regions
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Tirat Carmel Mental Health Center, Tirat Hacarmel 30200, Israel
Additional Information
Starting date: June 2009
Last updated: July 25, 2012
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