The purpose of this study is to examine the effects of a 10-week Omega-3 Fatty Acid treatment phase on brain chemistry of adolescents with major depressive disorder (MDD) using proton magnetic resonance imaging.

This study rests on a confluence of findings showing that: 1) Major depressive disorder (MDD), is a major public health concern that often emerges in adolescence; which entails 2) pathophysiological abnormalities in fronto-striatal structures resulting in death and atrophy of glia and neurons; 3) omega-3 fatty acids (FA) effects on brain function in adolescent MDD can be assessed by proton magnetic resonance spectroscopy (1H MRS); and, 4) it is critical that commonly used complementary and alternative medicines such as omega-3FA that have face validity be tested for their neurobiological effect in MDD.

Using 1H MRSI, this study examines the effects of Omega-3FA on striatal and anterior cingulate cortex (ACC) concentrations of the neurocellular biomarkers total choline (tCho), total creatine (tCr), and γ-aminobutyric acid (GABA, ACC only) in adolescent MDD. Hypotheses are: 1) relative to placebo, omega-3FA treatment will result in significant reductions of striatal and ACC tCho and tCr concentrations, and increased ACC GABA; 2: Regardless of treatment condition (placebo or Omega-3FA), MDD adolescents who are improved at the end of 10-week treatment will exhibit a significant decrease in striatal and ACC tCho and tCr concentrations, and increases in ACC GABA relative to unimproved adolescents.

Inclusion Criteria:

• 12 to 19 years old (inclusive) of both sexes and all ethnic/racial groups.
• DSM-IV-TR criteria for MDD
• MDD Duration of at least 8 weeks and a severity score of at least 40 on the CDRS-R.
• Age at first onset MDD of at least 12 years.
• No significant medical or neurological disorder
• For female subjects, negative pregnancy test at time of enrollment.
• Female subjects who are sexually active and not using a method of birth control will be excluded. Use of hormonal contraceptives (such as prescribed "birth control pills" or a prescribed birth control implant) is not exclusionary.
• Subjects must be able to swallow capsules.
• A minimum IQ of 80 will be required.

Exclusion Criteria:

• Current or Past DSM-IV-TR diagnoses of bipolar disorder, schizophrenia, psychosis, autism/pervasive developmental disorder (PDD), and Tourette's disorder (TD).
• Current diagnosis of eating disorder, panic disorder, obsessive-compulsive disorder (OCD), post traumatic stress disorder (PTSD), conduct disorder, and substance related disorders other than nicotine.
• Current suicidal ideation with intent or plan, or who may pose a danger to themselves.
• Current antidepressant treatment will be excluded. Past antidepressant treatment will not be exclusionary, so long as patients are off antidepressant medication for 60 days prior to study entry. No individual will be advised to terminate ongoing treatment.
• Certain short half-life medications, such as vitamins that contain unidentified ingredients, St. Johns Wort, S-adenosyl Methionine (SAM), clonidine, and some over-the-counter medications.
• A minimum of 90 days off of treatment with long half life medications, such as neuroleptics, prior to study entry is required. Stimulant medication treatment for ADHD will not be exclusionary.
• If adolescents have been in psychotherapy prior to their entry in the study, they will be allowed to continue with the treatment. However, psychotherapy cannot be initiated at the time of study entry.