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Brain serotonin transporter binding, plasma arachidonic acid and depression severity: A positron emission tomography study of major depression.

Authors
  • Gopaldas, Manesh1
  • Zanderigo, Francesca2
  • Zhan, Serena3
  • Ogden, R Todd4
  • Miller, Jeffrey M2
  • Rubin-Falcone, Harry2
  • Cooper, Thomas B5
  • Oquendo, Maria A6
  • Sullivan, Gregory7
  • Mann, J John8
  • Sublette, M Elizabeth9
  • 1 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United States. , (United States)
  • 2 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States. , (United States)
  • 3 Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, United States. , (United States)
  • 4 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, United States. , (United States)
  • 5 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States; Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States. , (United States)
  • 6 Psychiatry Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. , (United States)
  • 7 Tonix Pharmaceuticals Holding Corp, New York, NY, United States. , (United States)
  • 8 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States; Department of Radiology, Columbia University, New York, NY, United States. , (United States)
  • 9 Department of Psychiatry, Columbia University, New York, NY, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Journal of affective disorders
Publication Date
Oct 01, 2019
Volume
257
Pages
495–503
Identifiers
DOI: 10.1016/j.jad.2019.07.035
PMID: 31319341
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Serotonin transporter (5-HTT) binding and polyunsaturated fatty acids (PUFAs) are implicated in major depressive disorder (MDD). Links between the two systems in animal models have not been investigated in humans. Using positron emission tomography (PET) and [11C]DASB, we studied relationships between 5-HTT binding potential and plasma levels of PUFAs docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) in medication-free MDD patients (n = 21). PUFAs were quantified using transesterification and gas chromatography. Binding potential BPP, and alternative outcome measures BPF and BPND, were determined for [11C]DASB in six a priori brain regions of interest (ROIs) using likelihood estimation in graphical analysis (LEGA) to calculate radioligand total distribution volume (VT), and a validated hybrid deconvolution approach (HYDECA) that estimates radioligand non-displaceable distribution volume (VND) without a reference region. Linear mixed models used PUFA levels as predictors and binding potential measures as outcomes across the specified ROIs; age and sex as fixed effects; and subject as random effect to account for across-region binding correlations. As nonlinear relationships were observed, a quadratic term was added to final models. AA predicted both 5-HTT BPP and depression severity nonlinearly, described by an inverted U-shaped curve. 5-HTT binding potential mediated the relationship between AA and depression severity. Given the small sample and multiple comparisons, results require replication. Our findings suggest that AA status may impact depression pathophysiology through effects on serotonin transport. Future studies should examine whether these relationships explain therapeutic effects of PUFAs in the treatment of MDD. Copyright © 2019. Published by Elsevier B.V.

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