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.