Omega-3 Fatty Acids in Adolescents with Depression

Summary

Principal Investigator: Vilma Gabbay
Abstract: DESCRIPTION (provided by applicant): Objective. To provide preliminary data regarding the efficacy and tolerability of the omega-3 fatty acids (omega-3FA) docosahexaenoic acid (DMA) and eicosapentaenoic acid (EPA) in adolescents with major depression (MOD). Rationale. Evidence links central monoamine dysfunction, neurocellular alterations, and immune system dysregulation with MDD. Omega-3FA have been found to have powerful modulatory effects on central monoaminergic activity, are essential structural and functional components of neurons and glia, are effective anti-inflammatory agents, and may be effective in adult mood disorders. A body of epidemiological and neurobiological findings link omega-3FA and MDD. These related observations provide the basis for the proposed study. Hypothesis. Omega-3FA treatment is superior to placebo in adolescents with MDD. Methods. Subjects. 40 medically healthy, antidepressant na[unreadable]ve adolescents, ages 12-18, with MDD for at least 8 weeks and a minimum severity score of >40 on the CDRS-R, and onset of first episode > 12 years. Diagnosis. MDD will be established with the K-SADS-PL. Excluded will be current and past: bipolar disorder, schizophrenia, psychosis, autism, pervasive developmental disorder, .and Tourette's disorder; current post traumatic stress disorder, panic disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, conduct disorder, eating disorders, and substance related disorders. Study Treatments. Adolescents will be randomized to 10 weeks of double blind treatment with omega3-FA or matching placebo. Dose will be initiated at 1.2mg/d, titrated flexibly every 2 weeks up to a maximum of 3.6g/d. Omega3-FA will be combined EPA/DHA (ratio 2:1). A minimum of two weeks' duration at lower doses will provide the opportunity to assess clinical response at any one dose. Subjects will be followed weekly by a child psychiatrist. Assessments will include determination of MDD (K-SADS), MDD severity (Children's Depression Rating Scale-Revised [CDRS-R]), clinical global improvement (CGI), adverse events/vital signs, suicidal ideation, food intake checklist. Data Analyses. Two primary outcomes will be used to test the hypothesis: MDD severity indexed by CDRS total scores, and a CGI rating of 1 or 2 (Very Much or Much Improved). An intent to treat design will be applied, controlling for background food intake and other pertinent covariates, if appropriate. Significance. Adolescent MDD is associated with serious functional impairments, including suicide, and represents a major public health concern. In spite of its importance, it has been subject to relatively little biological research. This study stands at the confluence of current efforts to improve the treatment of adolescents with MDD and to develop alternative therapeutic approaches for this group. Should results of this pilot study suggest efficacy and tolerability of omega-3FA, we will plan a larger study to provide an adequate test of omega-3FA efficacy in this clinical population.
Funding Period: 2005-09-30 - 2009-08-31
more information: NIH RePORT

Top Publications

  1. pmc Striatum-based circuitry of adolescent depression and anhedonia
    Vilma Gabbay
    Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    J Am Acad Child Adolesc Psychiatry 52:628-41.e13. 2013
  2. pmc A double-blind, placebo-controlled trial of ω-3 fatty acids in Tourette's disorder
    Vilma Gabbay
    NYU Child Study Center, NYU School of Medicine, New York, New York, USA
    Pediatrics 129:e1493-500. 2012
  3. pmc Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia
    Vilma Gabbay
    Department of Child and Adolescent Psychiatry, New York University Child Study Center, New York University Langone Medical Center, New York, NY 10016, USA
    Arch Gen Psychiatry 69:139-49. 2012
  4. pmc The possible role of the kynurenine pathway in anhedonia in adolescents
    Vilma Gabbay
    Department of Child and Adolescent Psychiatry, NYU Child Study Center, NYU School of Medicine, New York University Langone Medical Center, 577 First Avenue, New York, NY 10016, USA
    J Neural Transm 119:253-60. 2012
  5. pmc The possible role of the kynurenine pathway in adolescent depression with melancholic features
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, NY 10016, USA
    J Child Psychol Psychiatry 51:935-43. 2010
  6. pmc The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, New York, New York, USA
    Prog Neuropsychopharmacol Biol Psychiatry 34:37-44. 2010
  7. pmc A preliminary study of functional connectivity in comorbid adolescent depression
    Kathryn R Cullen
    University of Minnesota Medical School, Department of Psychiatry, Minneapolis, MN, United States
    Neurosci Lett 460:227-31. 2009
  8. pmc A preliminary study of cytokines in suicidal and nonsuicidal adolescents with major depression
    Vilma Gabbay
    New York University School of Medicine, NYU Child Study Center, New York, New York 10016, USA
    J Child Adolesc Psychopharmacol 19:423-30. 2009
  9. pmc A cytokine study in children and adolescents with Tourette's disorder
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, 577 First Avenue, New York, NY 10016, USA
    Prog Neuropsychopharmacol Biol Psychiatry 33:967-71. 2009
  10. pmc Immune system dysregulation in adolescent major depressive disorder
    Vilma Gabbay
    New York University School of Medicine, NYU Child Study Center, NY 10016, United States
    J Affect Disord 115:177-82. 2009

Scientific Experts

  • Vilma Gabbay
  • Kathryn R Cullen
  • F Xavier Castellanos
  • Christopher J Bell
  • Dylan G Gee
  • Bryon A Mueller
  • Michael P Milham
  • Leslie Hulvershorn
  • Kelvin O Lim
  • Jazmin Camchong
  • Alaa Houri
  • Bonnie Klimes-Dougan
  • Sanjiv Kumra

Detail Information

Publications12

  1. pmc Striatum-based circuitry of adolescent depression and anhedonia
    Vilma Gabbay
    Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    J Am Acad Child Adolesc Psychiatry 52:628-41.e13. 2013
    ..Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity...
  2. pmc A double-blind, placebo-controlled trial of ω-3 fatty acids in Tourette's disorder
    Vilma Gabbay
    NYU Child Study Center, NYU School of Medicine, New York, New York, USA
    Pediatrics 129:e1493-500. 2012
    ..In a placebo-controlled trial, we examined the efficacy of O3FA in children and adolescents with TD...
  3. pmc Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia
    Vilma Gabbay
    Department of Child and Adolescent Psychiatry, New York University Child Study Center, New York University Langone Medical Center, New York, NY 10016, USA
    Arch Gen Psychiatry 69:139-49. 2012
    ..Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA)...
  4. pmc The possible role of the kynurenine pathway in anhedonia in adolescents
    Vilma Gabbay
    Department of Child and Adolescent Psychiatry, NYU Child Study Center, NYU School of Medicine, New York University Langone Medical Center, 577 First Avenue, New York, NY 10016, USA
    J Neural Transm 119:253-60. 2012
    ..These results emphasize the importance of dimensional approaches in the investigation of psychiatric disorders...
  5. pmc The possible role of the kynurenine pathway in adolescent depression with melancholic features
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, NY 10016, USA
    J Child Psychol Psychiatry 51:935-43. 2010
    ..e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites...
  6. pmc The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, New York, New York, USA
    Prog Neuropsychopharmacol Biol Psychiatry 34:37-44. 2010
    ....
  7. pmc A preliminary study of functional connectivity in comorbid adolescent depression
    Kathryn R Cullen
    University of Minnesota Medical School, Department of Psychiatry, Minneapolis, MN, United States
    Neurosci Lett 460:227-31. 2009
    ..We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD...
  8. pmc A preliminary study of cytokines in suicidal and nonsuicidal adolescents with major depression
    Vilma Gabbay
    New York University School of Medicine, NYU Child Study Center, New York, New York 10016, USA
    J Child Adolesc Psychopharmacol 19:423-30. 2009
    ....
  9. pmc A cytokine study in children and adolescents with Tourette's disorder
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, 577 First Avenue, New York, NY 10016, USA
    Prog Neuropsychopharmacol Biol Psychiatry 33:967-71. 2009
    ..We also explored whether comorbid obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients...
  10. pmc Immune system dysregulation in adolescent major depressive disorder
    Vilma Gabbay
    New York University School of Medicine, NYU Child Study Center, NY 10016, United States
    J Affect Disord 115:177-82. 2009
    ....
  11. pmc Lateralized caudate metabolic abnormalities in adolescent major depressive disorder: a proton MR spectroscopy study
    Vilma Gabbay
    NYU Child Study Center, Department of Psychiatry, New York University School of Medicine, 557 First Avenue, New York, NY 10016, USA
    Am J Psychiatry 164:1881-9. 2007
    ....