The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk.

Autor: Sublette ME; Department of Psychiatry, Columbia University, New York, NY, USA. elizabeth.sublette@nyspi.columbia.edu.; Molecular Imaging & Neuropathology Area, New York State Psychiatric Institute, New York, NY, USA. elizabeth.sublette@nyspi.columbia.edu., Daray FM; University of Buenos Aires, School of Medicine, Institute of Pharmacology, Buenos Aires, Argentina.; National Scientific and Technical Research Council, Buenos Aires, Argentina., Ganança L; Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Departamento de Psiquiatria e Saúde Mental, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal., Shaikh SR; Nutritional Obesity Research Center, Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Feb; Vol. 29 (2), pp. 269-286. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1038/s41380-023-02322-6
Abstrakt: Long-chain polyunsaturated fatty acids (LC-PUFAs) are obtained from diet or derived from essential shorter-chain fatty acids, and are crucial for brain development and functioning. Fundamentally, LC-PUFAs' neurobiological effects derive from their physicochemical characteristics, including length and double bond configuration, which differentiate LC-PUFA species and give rise to functional differences between n(omega)-3 and n-6 LC-PUFAs. LC-PUFA imbalances are implicated in psychiatric disorders, including major depression and suicide risk. Dietary intake and genetic variants in enzymes involved in biosynthesis of LC-PUFAs from shorter chain fatty acids influence LC-PUFA status. Domains impacted by LC-PUFAs include 1) cell signaling, 2) inflammation, and 3) bioenergetics. 1) As major constituents of lipid bilayers, LC-PUFAs are determinants of cell membrane properties of viscosity and order, affecting lipid rafts, which play a role in regulation of membrane-bound proteins involved in cell-cell signaling, including monoaminergic receptors and transporters. 2) The n-3:n-6 LC-PUFA balance profoundly influences inflammation. Generally, metabolic products of n-6 LC-PUFAs (eicosanoids) are pro-inflammatory, while those of n-3 LC-PUFAs (docosanoids) participate in the resolution of inflammation. Additionally, n-3 LC-PUFAs suppress microglial activation and the ensuing proinflammatory cascade. 3) N-3 LC-PUFAs in the inner mitochondrial membrane affect oxidative stress, suppressing production of and scavenging reactive oxygen species (ROS), with neuroprotective benefits. Until now, this wealth of knowledge about LC-PUFA biomechanisms has not been adequately tapped to develop translational studies of LC-PUFA clinical effects in humans. Future studies integrating neurobiological mechanisms with clinical outcomes may suggest ways to identify depressed individuals most likely to respond to n-3 LC-PUFA supplementation, and mechanistic research may generate new treatment strategies.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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