•Geographical distribution of deuterium correlates with depression rate.

•Deuterium depleted water reduces stress-induced depressive-like signs in mice.

•Hippocampal proliferation after stress is rescued by deuterium depleted water.

•Deuterium depleted water induces SSRI-like changes in EEG parameters of sleep.

•Above-indicated effects may be due to normalization of hippocampal 5-HTT level.

Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorderssuch 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 depres-sion was investigated, both epidemiologically, and in a mouse model of chronic mild stress. We performeda correlation analysis between deuterium content of tap water and rates of depression in regions of theUSA. Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted watertreatment (91 ppm) affects depressive-like behavior and hippocampal structure.

The effect of deuterium-depletion on sleep electrophysiology was also evaluated in naïve mice. There was a geographic correlationbetween a content of deuterium and the prevalence of depression across the USA. In the chronic stressmodel, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERTexpression 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 attenuatedin mice fed with deuterium-depleted water. Finally, in naïve mice, deuterium-depleted water treat-ment increased EEG indices of wakefulness, and decreased duration of REM sleep, phenomena that havebeen shown to result from the administration of selective serotonin reuptake inhibitors (SSRI).

Our datasuggest that the deuterium content of water may influence the incidence of affective disorder-relatedpathophysiology and major depression, which might be mediated by the serotoninergic mechanisms.© 2014 Published by Elsevier B.V.