Retinoic Acid Homeostasis in Neuropsychiatric Diseases

Study Overview
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Brief Summary
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It is hypothesized, that local retinoic acid (RA) homeostasis is functionally involved in the pathophysiology of depression. In a cross-sectional (and partly longitudinal) analysis, serum RA status will be assessed in healthy controls and subjects with Major Depression, Alzheimer's disease, alcoholism and in subjects with schizophrenia.

Detailed Description
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Retinoids comprise of a group of small-molecule derivatives of Vitamin A with retinoic acid (RA) representing the biologically most active endogenous form. RA has multiple functions central nervous system (CNS). It is hypothesized, that local RA homeostasis is functionally involved in the pathophysiology of numerous neuropsychiatric diseases.

Official Title
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Retinoic Acid Homeostasis in Neuropsychiatric Diseases

Conditions
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Major Depression, Alzheimer's Disease, Alcoholism, Schizophrenia

Participation Criteria
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Eligibility Criteria
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MDD-Group Inclusion Criteria: depressive episode in the context of unipolar major depression at least 18 points or more on the BDI and HAMD-17 Exclusion Criteria: additional or comorbid axis-I or axis-II disorder current history of any neurological or other serious medical condition any psychopharmacological treatment or substance use within the last two weeks or 5 half-lives (whichever is longer) of the respective substance any oral or topical application of retinoid-containing preparations within the last 3 months AD-Group Inclusion Criteria: diagnosed AD Exclusion Criteria: any other neurodegenerative disorder any oral or topical application of retinoid-containing preparations within the last 3 months Schizophrenia-Group Inclusion Criteria: subjects with schizophrenia intended therapy with clozapine, olanzapine or aripiprazole BMI: 18 - 29,9 kg/m2 Exclusion Criteria: presence of diabetes or pathological glucose tolerance presence of and chronic inflammatory disease any psychopharmacological treatment of clozapine, olanzapine or aripiprazole within the last 3 months any oral or topical application of retinoid-containing preparations within the last 3 months Alcoholism-Group Inclusion Criteria: subjects with alcoholism who either still consume alcohol or are abstinent for at least 4 weeks Exclusion Criteria: any oral or topical application of retinoid-containing preparations within the last 3 months current history of any neurological or other serious medical condition despite liver diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD<br>Currently unmedicated patients with a depressive episode in the context of unipolar major depression | |
| Control<br>Healthy Controls | |
| Alzheimer's Disease<br>Patients with Alzheimer's disease | |
| Alcoholism<br>Subjects with alcoholism | |
| Schizophrenia<br>Subjects with before and schizophrenia prior to and during medication with clozapine, olanzapine or aripiprazole | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum retinoic acid (RA) levels [nM] | Serum retinoic acid levels [nM] as determined by HPLC according to previously published protocols | Week 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For MDD group: MADRS | Questionnaire to assess symptom severity in MDD | Week 1, 3, 6 | 
| For MDD group: BDI II | Self-rating to assess of symptom severity in MDD | Week 1, 3, 6 | 
| For MDD and schizophrenia Group: Change of serum retinoic acid (RA) levels [nM] | Serum retinoic acid levels [nM] as determined by HPLC according to previously published protocols | Week 1, 3, 6 | 
| For schizophrenia group: Positive and Negative Syndrome Scale (PANSS) for Schizophrenia | Measurement of symptom severity of patients with schizophrenia | Week 1, 3, 6 | 
| For schizophrenia group: Change of metabolic parametres For schizophrenia group:Positive and Negative Syndrome Scale (PANSS) | Assessmant of weight, blood pressure, levels of Glucose, HbA1c, cholesterols and dietry | Week 1, 3, 6 |