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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00944996

Enrollment

100

Registered

2009-07-23

Start date

2009-06-30

Completion date

2012-07-31

Last updated

2012-07-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

DRUGSSRI; SNRI; TCA

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	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)

Countries

Israel

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026