Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Major Depression |
Drug: SSRI; SNRI; TCA |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Investigator, Outcomes Assessor) Primary Purpose: Basic Science |
| Official Title: | Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression |
- Measurements of PACAP and BDNF serum levels [ Time Frame: 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) ] [ Designated as safety issue: No ]
- Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions [ Time Frame: 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) ] [ Designated as safety issue: No ]
| Enrollment: | 100 |
| Study Start Date: | June 2009 |
| Study Completion Date: | July 2012 |
| Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: antidepressant |
Drug: SSRI; SNRI; TCA
Tablets or Pills, 1 or 2 per day, more than 2 month
Other Names:
|
| No Intervention: Healthy volunteers |
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations| Israel | |
| Tirat Carmel Mental Health Center | |
| Tirat Hacarmel, Israel, 30200 | |
| Study Chair: | Anatoly Kreinin, MD, PhD | The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa |
| Principal Investigator: | Albert Pinhasov, PhD | Department of Molecular Biology at Ariel University Center |
| Principal Investigator: | Leon Raskin, PhD | University of Michigan |
| Principal Investigator: | Kamal Farhat, MD | The Nazareth Hospital-EMMS |
| Principal Investigator: | Joseph Farah, MD | The Nazareth Hospital-EMMS |
| Principal Investigator: | Klaudia Rybalksy, MD | The Nazareth Hospital-EMMS |
More Information
No publications provided
| Responsible Party: | Anatoly Dr. Kreinin, Director of Psychiatric Department, Tirat Carmel Mental Health Center |
| ClinicalTrials.gov Identifier: | NCT00944996 History of Changes |
| Other Study ID Numbers: | akparl08, 920080174, 040-2008 |
| Study First Received: | July 19, 2009 |
| Last Updated: | July 25, 2012 |
| Health Authority: | Israel: Ministry of Health |
Keywords provided by Tirat Carmel Mental Health Center:
|
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 |
Additional relevant MeSH terms:
|
Depression Depressive Disorder Depressive Disorder, Major Behavioral Symptoms Mood Disorders Mental Disorders Antidepressive Agents Pituitary Adenylate Cyclase-Activating Polypeptide Psychotropic Drugs |
Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Vasodilator Agents Cardiovascular Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Growth Substances |
ClinicalTrials.gov processed this record on May 16, 2013