Glutamate Probes in Adolescent Depression


About this study

The purpose of this study is to learn if measures of brain chemicals from a brain scan called Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) and brain activity (known as cortical excitability and inhibition) collected by Transcranial Magnetic Stimulation (TMS) are different in adolescents with depression who are in different stages of treatment. Researchers are conducting this study to learn more about how the brain works in adolescents with depression and without depression (healthy controls). This is important because it may identify a biological marker (a measure of how bad an illness is) for depression that could one day be used to identify depressed adolescents who would benefit from certain treatments (medications for example) or to monitor how well treatments are working.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Adolescents from the ages of 13 to 21, male or female.
  • Subjects with MDD (Groups 2,3 & 4):

    • Must have a diagnosis of Major Depressive Disorder (MDD)

      • Single episode or recurrent; moderate to severe.
    • Must have a Childhood Depression Rating Scale-Revised (CDRS-R) score of ≥ 40.
    • Must have a Clinical Global Impression Severity (CGI-S) Scale of ≥ 4
  • Group 1: (Healthy Controls; 50 Subjects): Healthy volunteers who are 13-21 years of age with no current or lifetime mental health diagnoses and no current or lifetime psychotropic medication treatment.
  • Group 2: (50 subjects): Subjects with moderate to severe MDD who have initiated treatment with an SSRI no more than 7 days prior to the baseline visit.

    • Subjects and parents in group 2 will be eligible to return in 6-8 weeks for a follow up visit that includes mood assessments and evaluations.
    • Subjects who have been adherent to their clinically prescribed medication will be eligible for a second MRI/MRS scan and TMS measures within 7 days of the second visit.
  • Group 3: (50 subjects): Subjects with moderate to severe MDD that has responded to treatment with an SSRI.

    • Response will be defined as a 1 (very much) or 2 (much) improved on a CGI-Improvement Scale. This is the current acceptable standard in child and adolescent psychopharmacological research.

  • Group 4: (50 subjects): Subjects with moderate to severe MDD that has not responded to treatment with an SSRI as defined above with CGI scale score.
  • Subject and parent or guardian (if under age 18) must be capable of providing informed consent
  • Subjects must be right-handed.
  • Subjects and at least 1 parent must be fluent in English. • Subjects 18 years of age or older do not require an English-speaking parent

Exclusion Criteria:

  • Exclusion Criteria For all Subjects:

    • Contraindications to MRI/MRS, as determined by the MRI safety screen and MRI safety codes.
    • Subjects who are judged by the Principal Investigator to be at imminent risk for self-harm or suicide as indicated by interview or C-SSRS.
    • Pregnancy or suspected pregnancy in females.
    • Metal in the head (except the mouth*), implanted medication pumps, cardiac pacemaker

      • Subjects with braces will be excluded from MRI/MRS portion of the study only
    • Prior brain surgery.
    • Risk for increased intracranial pressure such as a brain tumor.
    • Any unstable medical condition.
  • Exclusion Criteria for Healthy Control Group only:

    • Current or past mental health diagnoses in subjects or first degree relatives of subjects.
    • Current or past mental health medications.
  • Exclusion Criteria for MDD Groups only:

    • Primary Axis I or II disorder other than MDD.
    • Unprovoked seizure history, seizure disorder, history of febrile seizures, first degree relative with epilepsy
    • Taking medication(s) that lower seizure threshold
    • Any significant findings on the TMS adult safety screen (TASS).
  • Exclusion Criteria for Group 2 only:

    • Subject has started SSRI medication more than 7 days prior to the baseline visit.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Paul Croarkin, D.O., M.S.

Closed for enrollment

More information


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