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| ID | Type | Description | Link |
|---|---|---|---|
| 920080174 | |||
| 040-2008 |
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| Name | Class |
|---|---|
| University of Michigan | OTHER |
| Ariel University | OTHER |
| The Nazareth Hospital, Israel | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| antidepressant | Active Comparator |
| |
| Healthy volunteers | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SSRI; SNRI; TCA | Drug | Tablets or Pills, 1 or 2 per day, more than 2 month |
|
| Measure | Description | 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) |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anatoly Kreinin, MD, PhD | The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa | Study Chair |
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tirat Carmel Mental Health Center | Tirat Hacarmel | 30200 | Israel |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D017367 | Selective Serotonin Reuptake Inhibitors |
| D000068760 | Serotonin and Noradrenaline Reuptake Inhibitors |
| D017374 | Paroxetine |
| D005473 | Fluoxetine |
| D020280 | Sertraline |
| D000089983 | Escitalopram |
| D015283 | Citalopram |
| D000069470 | Venlafaxine Hydrochloride |
| D002997 | Clomipramine |
| ID | Term |
|---|---|
| D014179 | Neurotransmitter Uptake Inhibitors |
| D049990 | Membrane Transport Modulators |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D018377 | Neurotransmitter Agents |
| D018490 | Serotonin Agents |
| D045505 | Physiological Effects of Drugs |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D015057 | 1-Naphthylamine |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D009570 | Nitriles |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D008055 | Lipids |
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
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