The Role Of Omega-3 Fatty Acids In Adolescent Depression

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.