Functional and Metabolic Changes in the Course of Antidepressive Treatment

Study Overview
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Brief Summary
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The study will investigate functional and metabolic changes in the course of antidepressive treatments. The investigators will apply different imaging methods to investigate the effects of antidepressive interventions on resting state neural activity, functional activation during cognitive and emotional stimulation, neurotransmitter concentrations as well as concentrations of brain- derived neurotrophic factor.

Detailed Description
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The study will investigate functional and metabolic changes in the course of antidepressive treatments. The investigators will apply different imaging methods to investigate the effects of antidepressive interventions on resting state neural activity, functional activiation during cognitive and emotional stimulation, neurotransmitter concentrations as well as concentrations of brain- derived neurotrophic factor. The investigators hypothesize that antidepressive interventions modulate the excitatory glutamatergic system and thereby increase either the concentration of glutamate or the glutamate/ glutamine ratio. These metabolic changes are accompanied by altered functional activation in medial and lateral prefrontal areas during emotional and cognitive stimulation, respectively. After longterm treatment, excitatory glutamate and inhibitory gamma-aminobutyric acid concentrations adapt to a new homeostatic level which is reflected in antidepressive response or remission of symptoms. The investigators assume that the levels of glutamate and gamma-aminobutyric acid determine the amplitude of BOLD responses during emotional and cognitive stimulation. Furthermore, the investigators hypothesize that the plasma concentration of brain- derived neurotrophic factor might be a predictor for therapy response and changes in the course of treatment. With our protocol we adhere to the rules of good scientific practice and observe all relevant laws, regulations and guidelines that pertain to the project. The investigators' study is in compliance with the Declaration of Helsinki and approved by the local ethics committee. Storage of data is in accordance with german privacy laws.

Conditions
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Major Depressive Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18- 65 years current depressive episode males and females Intelligence quotient > 80 written informed consent Exclusion Criteria: neurological or psychiatric disease other than major depressive disorder metal implants, pacemaker, intracranial clips agoraphobia history of serious head injury

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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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurotransmitter concentrations (glutamate, glutamine, gamma-aminobutyric acid) from baseline to response to antidepressive intervention | Neurotransmitter concentrations will be measured at 3 timepoints (at baseline, after the first antidepressive intervention and after patients show response or remission of symptoms). Measurements will show whether antidepressive interventions modulate the excitatory glutamatergic system and thereby increase either the concentration of glutamate or the glutamate/ glutamine ratio. After longterm treatment, excitatory glutamate and inhibitory gamma-aminobutyric acid concentrations are hypothesized to adapt to a new homeostatic level which is reflected in antidepressive response or remission of symptoms. | Neurotransmitter concentrations will be measured at baseline (T0), after the first antidepressive intervention (T1; 24- 48 hrs. after baseline measurement) and after patients show response or remission of symptoms (T2; an expected average of 2- 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neuronal activation patterns from baseline to response to antidepressive intervention | Neuronal activation patterns will be measured at 3 timepoints (at baseline, after the first antidepressive intervention and after patients show response or remission of symptoms). Measurements will show whether antidepressive interventions modulate resting state neural activity and functional activiation during cognitive and emotional stimulation. We expect changes in neurotransmitter concentrations to be accompanied by altered functional activation in medial and lateral prefrontal areas during emotional and cognitive stimulation, respectively. Furthermore, levels of glutamate and gamma-aminobutyric acid are hypothesized to determine the amplitude of BOLD responses during emotional and cognitive stimulation. | Measurements will be conducted at baseline (T0), after the first antidepressive intervention (T1; 24- 48 hrs. after baseline measurement) and after patients show response or remission of symptoms (T2; an expected average of 2- 4 weeks) |