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

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

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.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Dept of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Depressed, unmedicated; Participants with MDD who are not treated with any antidepressant medication
Depressed, on antidepressant; Participants with MDD, currently depressed but on a stable dose of an SSRI antidepressant
Healthy control; Healthy participant with no MDD or other psychiatric condition, matched by age and gender to MDD participants

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Paul Carlson
• Collaborators: University of Utah; Western Institute for Biomedical Research; Molecular Imaging Program, Huntsman Cancer Institute
• Investigators: Principal Investigator: Paul J Carlson, M.D., University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2011
• Primary Completion (Actual): June 24, 2012
• Study Completion (Actual): June 24, 2012

Study Registration Dates

• First Submitted: November 1, 2011
• First Submitted That Met QC Criteria: November 3, 2011
• First Posted (Estimate): November 4, 2011

Study Record Updates

• Last Update Posted (Actual): May 19, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Depression; Magnetic resonance spectroscopy; glucose metabolism; Positron emission tomography; ATP; phosphocreatine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: WIBR08-PJC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified scanning images may be individually examined after the study is completed if new analysis methods become available to collaborators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No