Use of Multiple Brain Imaging Modalities (PET and MRS) to Identify Metabolic Abnormalities in Major Depression

Study Overview
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Brief Summary
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Several lines of evidence support the existence of an underlying abnormality in brain energy metabolism may play a key role in the biology of mood disorders. The current study utilizes two distinct but complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and multinuclear magnetic resonance spectroscopy (MRS), to better understand the nature of these metabolic abnormalities in major depressive disorder (MDD). The investigators hypothesize that individuals with depression will have increased metabolic activity as measured by PET in certain brain regions involved in mood regulation, but that this metabolic activity will be inefficient based on MRS findings. For this study, the investigators will study 10 medication-free, currently depressed participants with recurrent MDD, 10 depressed participants with recurrent MDD currently taking antidepressant medication, and up to 20 healthy control participants matched to depressed participants for age and gender. Depressed and healthy participants will each undergo one PET scan and one MRS scanning session.

Official Title
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Comparison of Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and Magnetic Resonance Spectroscopy (MRS) as Bioenergetic Imaging Modalities in Healthy Human Brain and Major Depressive Disorder

Conditions
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Major Depressive Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet DSM-IV criteria for Major Depressive Disorder (MDD), Recurrent Montgomery-Asberg Depression Rating Scale (MADRS) score > 18 Exclusion Criteria: Any coexisting psychiatric illness other than generalized anxiety disorder, panic disorder, or social/specific phobias Any history of substance dependence Substance abuse within the past 6 months Significant risk of suicide, as defined by score >4 on item 10 of the MADRS or in the clinical judgment of the study physician Any significant medical or neurological condition which is likely to impact the central nervous system and/or affect the results of MRS or PET imaging For the subset of unmedicated MDD patients, any psychotropic medications within 4 weeks prior to scanning. For the subgroup of medicated patients, they may be taking a stable dose (i.e., same dose for at least 4 weeks at the time of scanning) of standard antidepressant medications, but may not be taking any other psychotropic medication. Inability to give informed consent Contraindication to MRI (e.g., pacemaker, ferromagnetic implants in the body)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Depressed, unmedicated<br>Participants with MDD who are not treated with any antidepressant medication | |
| Depressed, on antidepressant<br>Participants with MDD, currently depressed but on a stable dose of an SSRI antidepressant | |
| Healthy control<br>Healthy participant with no MDD or other psychiatric condition, matched by age and gender to MDD participants | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| high energy phosphate metabolites (Phosphocreatine (PCr)) as measured by magnetic resonance spectroscopy | relative concentration of Pcr | cross-sectional | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| regional cerebral glucose metabolism, as measured by Positron Emission Tomography (PET) | binding potential of FDG | cross-sectional | 
| N-Acetyl-Aspartate (NAA) metabolite intensity, as measured by proton Magnetic Resonance Spectroscopy (MRS) | relative concentration of NAA | cross-sectional | 
| severity of depressive symptoms, as scored on the Montgomery-Asberg Depression Rating Scale (MADRS) | MADRS composite score | cross-sectional | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Positron emission tomography, Magnetic resonance spectroscopy, glucose metabolism, ATP, phosphocreatine