title: Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression.
abstract: White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA.
authors.forename: Binod Thapa
authors.initials: BT
authors.lastname: Chhetry
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Hezghia
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Department of Biostatistics, Columbia University, 722 West 168th St., New York, NY 10032, USA.
authors.forename: Seonjoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Rubin-Falcone
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA; Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA; Department of Radiology, Columbia University, 622 West 168th St, New York, NY, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA. Electronic address: sublett@nyspi.columbia.edu.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sublette
mesh_terms: D000328:Adult; D016880:Anisotropy; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000178:diet therapy*; D019587:Dietary Supplements; D056324:Diffusion Tensor Imaging; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D018709:Statistics, Nonparametric; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3
keywords: DTI; Docosahexaenoic acid; Fractional anisotropy; Major depressive disorder; Omega-3; PUFA