Glutamate Probes in Adolescent Depression

NCT02307617 | Completed DMC

• 1 other identifier: 14-004662
• Study Type: observational
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder; Major Depressive Disorder, Recurrent; Major Depressive Disorder, Remitted

Keywords

Major depressive disorder; MDD; healthy control; selective serotonin reuptake inhibitor; SSRI; depression; transcranial magnetic stimulation; TMS; magnetic resonance spectroscopy; MRS; adolescent; mild MDD; mild depression; cortical excitability; cortical inhibition; cortical silent period; motor threshold; intracortical facilitation; intracortical inhibition; motor cortex; dorsolateral prefrontal cortex; DLPFC; thumb twitch; gamma aminobutyric acid; GABA; glutamate; single pulse; paired pulse

Outcome Measures

Primary Outcomes (2)

• Concentrations of GABA and glutamate in the brains of adolescents with MDD.

  Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.

  Baseline

• The change of GABA and glutamate concentrations in adolescents with MDD after 6 weeks of SSRI treatment.

  Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.

  Baseline to 6 weeks (group 2)

Secondary Outcomes (2)

• The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD

  Baseline

• The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD after 6 weeks of SSRI treatment.

  Baseline to 6 weeks (group 2)

Study Arms (4)

Group 2

Adolescent participants who plan to start selective serotonin reuptake inhibitor (SSRI) treatment for their depression. Data will be collected prior to the start of the medication and again 6 weeks after the start of the medication.

Medication Responders

Adolescent participants who have responded to SSRI treatment for their depression.

Medication Non-Responders

Adolescent participants with depression that has not responded to SSRI treatment.

Healthy Controls

Adolescent participants who have no current or past mental health diagnoses.

Eligibility Criteria

• Age: 13 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This protocol will plan to screen depressed children and adolescents who are seeking treatment at Mayo Clinic in Rochester, MN, using strict inclusion and exclusion criteria. These adolescents will represent gender and minority distribution consistent with the Rochester metro/rural area demographic distribution. This study will be inclusive of all races, genders, and socioeconomic classes.

You may qualify if:

• 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.
• The MDD diagnosis is based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children - Past and Lifetime (K-SADS-PL).
• This semi-structured psychiatric interview will be administered by a psychiatrist, Ph.D. level psychologist, or equivalent professional with extensive clinical experience.
• 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 for which an SSRI has been clinically indicated.
• If initiating SSRI treatment, medication must be started ± 7 days of 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.
• Subjects who choose not to initiate treatment with an SSRI will have a baseline visit only
• Subjects who discontinue or change their medication after the baseline will not be eligible for a follow-up visit

You may not qualify if:

• 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.
• Current or past mental health diagnoses in subjects or first degree relatives of subjects.
• Current or past mental health medications.
• 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).
• \. Subject has started SSRI medication more than 7 days prior to the baseline visit.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Depressive Disorder, Major; Recurrence; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Paul E Croarkin, D.O.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: December 4, 2014
• Study Start: August 1, 2014
• Primary Completion: April 17, 2017
• Study Completion: April 17, 2017
• Last Updated: April 23, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)