title: Deuterium content of water increases depression susceptibility: the potential role of a serotonin-related mechanism.
abstract: Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus the link between deuterium content of water and depression was investigated, both epidemiologically, and in a mouse model of chronic mild stress. We performed a correlation analysis between deuterium content of tap water and rates of depression in regions of the USA. Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted water treatment (91 ppm) affects depressive-like behavior and hippocampal SERT. The effect of deuterium-depletion on sleep electrophysiology was also evaluated in naïve mice. There was a geographic correlation between a content of deuterium and the prevalence of depression across the USA. In the chronic stress model, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERT expression was decreased in mice treated with deuterium-treated water compared with regular water. Five days of predator stress also suppressed proliferation in the dentate gyrus; this effect was attenuated in mice fed with deuterium-depleted water. Finally, in naïve mice, deuterium-depleted water treatment increased EEG indices of wakefulness, and decreased duration of REM sleep, phenomena that have been shown to result from the administration of selective serotonin reuptake inhibitors (SSRI). Our data suggest that the deuterium content of water may influence the incidence of affective disorder-related pathophysiology and major depression, which might be mediated by the serotoninergic mechanisms.
authors.affiliation: Department of Pharmacology, Oxford University, Oxford, UK; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Portugal; School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Maastricht, Netherlands. Electronic address: bioc0541@pharm.ox.ac.uk.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Strekalova
authors.affiliation: Department of Pharmacology, Oxford University, Oxford, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Evans
authors.affiliation: Laboratory of Cognitive Dysfunctions, Institute of General Pathology and Pathophysiology, Moscow, Russia; Timantti AB, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Chernopiatko
authors.affiliation: Department of Pharmacology, Oxford University, Oxford, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Couch
authors.affiliation: Institute for Hygiene and Tropical Medicine, New University of Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Costa-Nunes
authors.affiliation: Claude Bernard University, Faculty of Medicine, EA 4170 Lyon, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
authors.affiliation: IsoForensics Inc., Salt Lake City, UT, USA.
authors.forename: Lesley
authors.initials: L
authors.lastname: Chesson
authors.affiliation: GIGA Neuroscience, University of Liege, Liege, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Vignisse
authors.affiliation: School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Maastricht, Netherlands.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: Department of Pharmacology, Oxford University, Oxford, UK.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.affiliation: Laboratory of Cognitive Dysfunctions, Institute of General Pathology and Pathophysiology, Moscow, Russia; Timantti AB, Stockholm, Sweden.
authors.forename: Igor
authors.initials: I
authors.lastname: Pomytkin
authors.affiliation: School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Maastricht, Netherlands; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. Electronic address: kplesch@mail.uni-wuerzburg.de.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000818:Animals; D003863:Depression / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology*; D003903:Deuterium / Q000633:toxicity*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014867:Water / Q000737:chemistry*
chemical_list: D003903:Deuterium; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014867:Water
keywords: Chronic stress; Depression; Deuterium; Hippocampal cell proliferation; SERT; Sleep