The applicant is seeking to become an independent investigator focusing on the role of dietary essential polyunsaturated fatty acids (PUFAs) in the neurobiology of mood disorders and suicide, using positron emission tomography (PET). PROJECT DESIGN: Background.- PUFAs are implicated in mood disorders: 1) Low plasma levels of omega-3 PUFAs and higher ratios of omega-6 to omega-3 PUFAs have been found among depressed patients, and our pilot study suggests these indices predict suicide attempts. 2) Double-blinded, placebo-controlled studies have found that adding omega-3 fatty acids (fish oil) to standard treatment of depression improves outcomes in Major Depressive and Bipolar Disorders. 3) We find that similar brain regions have low glucose uptake among suicide attempters and in depressed patients with low fatty acids. Hypothesis: A functional imbalance between omega-3 and omega-6 PUFAs contributes to depression and suicidality. The objective is to clarify relationships between plasma PUFA levels, clinical characteristics, including suicide risk, and regional cerebral rates of glucose metabolism (rCMRglu) in Major Depressive Disorder.
Aim1. In regions of interest (ROIs), test the following hypotheses: a) Lower rCMRglu correlates with lower plasma PUFAs in depressed subjects b). rCMRglu are lower in suicide attempters vs. non-attempters.
Aim 2. Perform voxel-level analyses on rCMRglu and plasma PUFA levels in: a) Depressed subjects vs. healthy volunteers, b) Depressed subjects with and without suicide attempt history.
Aim 3. Perform voxel-level analyses of effects of augmentation treatment with fish oil on rCMRglu, plasma PUFA levels, symptom severity, and the relationships between them.
Aim 4. Characterize the effects offish oil on plasma PUFAs and clinical status: a) Test the hypothesis that plasma levels of DMA will be lower in depressed subjects than healthy volunteers, and lower in suicide attempters than nonattempters. b) Assess overall clinical status and severity of individual symptoms. Methods: Thirty subjects with Major Depressive Disorder (half with history of suicide attempt) not responding to treatment and 15 healthy volunteers will have quantitative PET scanning with [18F]FDG before and after adjunctive treatment for 4-6 weeks with fish oil. We will perform group comparisons of rCMRglu in ROIs and use statistical parametric mapping at the voxel level to generate difference and correlational maps. TRAINING: The candidate proposes to undertake specialized studies in neuroimaging methodologies, statistics, and lipid biochemistry.
Major Depressive Disorder and suicide are major public health problems worldwide. This study is expected to contribute to understanding the neurobiology of depression and may provide new information relevant to treatment with dietary fatty acids.
|Liu, Joanne J; Green, Pnina; John Mann, J et al. (2015) Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease. Brain Res 1597:220-46|
|Beier, Anne Mette; Lauritzen, Lotte; Galfalvy, Hanga C et al. (2014) Low plasma eicosapentaenoic acid levels are associated with elevated trait aggression and impulsivity in major depressive disorder with a history of comorbid substance use disorder. J Psychiatr Res 57:133-40|
|Sublette, M Elizabeth; Galfalvy, Hanga C; Hibbeln, Joseph R et al. (2014) Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder. Int J Neuropsychopharmacol 17:383-91|
|Olvet, Doreen M; Peruzzo, Denis; Thapa-Chhetry, Binod et al. (2014) A diffusion tensor imaging study of suicide attempters. J Psychiatr Res 51:60-7|
|Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A et al. (2014) Cortical thickness differences between bipolar depression and major depressive disorder. Bipolar Disord 16:378-88|
|Liu, Joanne J; Galfalvy, Hanga C; Cooper, Thomas B et al. (2013) Omega-3 polyunsaturated fatty acid (PUFA) status in major depressive disorder with comorbid anxiety disorders. J Clin Psychiatry 74:732-8|
|Sublette, M Elizabeth; Milak, Matthew S; Galfalvy, Hanga C et al. (2013) Regional brain glucose uptake distinguishes suicide attempters from non-attempters in major depression. Arch Suicide Res 17:434-47|
|Sublette, M Elizabeth; Ellis, Steven P; Geant, Amy L et al. (2011) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 72:1577-84|
|Sublette, M Elizabeth; Segal-Isaacson, C J; Cooper, Thomas B et al. (2011) Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturated fatty acids in subjects with and without major depressive disorder. J Am Diet Assoc 111:117-123.e1-2|
|Sublette, M Elizabeth; Galfalvy, Hanga C; Fuchs, Dietmar et al. (2011) Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav Immun 25:1272-8|
Showing the most recent 10 out of 11 publications