Neurochemical Effects of Omega-3 Fatty Acids in Adolescents at Risk for Mania

• Ages 10-21 years old.
• At least one biological parent with bipolar I disorder.
• Meets DSM-IV-TR 80 criteria for major depressive disorder (MDD or Depressive Disorder NOS at screening as determined by the Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, WASH-U-KSADS;81
• Childhood Depression Rating Scale-Revised Version40,41(CDRS-R) scores greater than or equal to 40 at screening and baseline.
• Fluent in English.
• Provision of written informed consent/assent as previously described.
• Agrees to use one of the following method of birth control: complete abstinence from sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive.

Exclusion Criterion:

• Contraindication to an MRI scan (e.g., metal clips, braces or claustrophobia).
• Mood symptoms resulting from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by careful medical evaluation or rapid symptom resolution.
• Psychotic symptoms (i.e., hallucinations or delusions).
• Any lifetime history of a manic or hypomanic episode.
• Any lifetime diagnosis of bipolar disorder not otherwise specified (NOS) or cyclothymia or a current diagnosis of depressive disorder NOS. A current diagnosis of dysthymia will not be exclusionary, if the adolescent also has a current diagnosis of MDD.
• A history of a major medical (e.g. diabetes) or neurological illness, laboratory abnormalities, or a significant episode (> 10 minutes) of loss of consciousness that could influence the MRS results, as determined by a study physician.
• Any history of alcohol or drug dependence (nicotine dependence is permitted).
• Allergy to shellfish or seafood.
• Mental retardation (IQ\<70) as determined by the Wechsler Abbreviated Scale of Intelligence (WASI), administered by a research coordinator who is a trained psychometrician.
• A positive serum pregnancy test or lactating.
• A history of intolerance, hypersensitivity or non-response to omega-3 fatty acids.
• Any history of a hematological disorder in themselves or a first-degree relative, since omega-3 fatty acids may be associated with anti-coagulant effects.
• Concomitant use of medications with anticoagulant effects (e.g. aspirin).
• A lithium or valproate serum level of >0.4 mEq/L and 30 mg/L, respectively at baseline.
• Use of antipsychotics, other mood stabilizers, stimulants (if opting to discontinue), or atomoxetine within 72 hours (aripiprazole within two weeks will be exclusionary because of its long half-life) or antidepressants within 5 days (fluoxetine within one month will be exclusionary because of its long half-life). Patients treated with a depot antipsychotic within one dosing interval of baseline will be excluded. Subjects diagnosed with ADHD and taking a stable dose of stimulants for the previous month will be permitted to continue if it is determined necessary by subject, primary caregiver, and treating clinician report in conjunction with the study physician.
• Concomitant use of other psychotropic medications or medications with central nervous system (CNS) effects within 5 half-lives from baseline MRI scan or prior treatment with a medication with CNS effects that requires more than 5 days of a screening period.
• Any psychiatric symptom that requires admission to an inpatient psychiatric hospital, as determined by a study physician.
• Any initiated psychotherapy within 2 months prior to the screening visit, or plans to initiate psychotherapy during study participation. Adolescents who present with their current depressive episode despite longer-term psychotherapy (i.e., >2 months) may be included. For participants who enter the study on psychotherapy, the type and frequency of therapy will remain constant during the study.