Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial

Bloch, Yehudit; Belmaker, Robert H.; Shvartzman, Pesach; Romem, Pnina; Bolotin, Arkady; Bersudsky, Yuly; Azab, Abed N.

doi:10.1038/s41598-021-98245-9

Cited by 6 publications

(4 citation statements)

References 81 publications

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“…On the other hand, the effects of O 2 on neuronal excitability in young healthy men were described as dose-dependent: 0.7 bar O 2 did not affect cFFF, 1.4 bar O 2 significantly jeopardized cFFFs, while 2.8 bar O 2 allowed for recovery of cFFF [50]. These results on oxygen are concerning, especially considering that normobaric oxygen is widely used in clinical settings [101,102], and a partial pressure of 1.4 bar is considered a safe upper limit for divers [103].…”

Section: Breathing Gasesmentioning

confidence: 99%

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review

Muth

Schipke

Brebeck³

et al. 2023

Medicina

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The critical flicker fusion frequency (cFFF) refers to the frequency at which a regularly recurring change of light stimuli is perceived as steady. The cFFF threshold is often assessed in clinics to evaluate the temporal characteristics of the visual system, making it a common test for eye diseases. Additionally, it serves as a helpful diagnostic tool for various neurological and internal diseases. In the field of diving/hyperbaric medicine, cFFF has been utilized to determine alertness and cognitive functions. Changes in the cFFF threshold have been linked to the influence of increased respiratory gas partial pressures, although there exist inconsistent results regarding this effect. Moreover, the use of flicker devices has produced mixed outcomes in previous studies. This narrative review aims to explore confounding factors that may affect the accuracy of cFFF threshold measurements, particularly in open-field studies. We identify five broad categories of such factors, including (1) participant characteristics, (2) optical factors, (3) smoking/drug use, (4) environmental aspects, and (5) breathing gases and partial pressures. We also discuss the application of cFFF measurements in the field of diving and hyperbaric medicine. In addition, we provide recommendations for interpreting changes in the cFFF threshold and how they are reported in research studies.

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Section: Breathing Gasesmentioning

confidence: 99%

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review

Muth

Schipke

Brebeck³

et al. 2023

Medicina

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“…The open-label design of the trial may also constitute a limitation since it is unknown whether changes in ACC connectivity may also occur in responders to placebo. The use of EMONO can be considered a limitation in that we cannot disentangle the speci c effect of N 2 O over oxygen and we cannot strictly ruled out the possibility that enriched oxygen have contributed to brain changes, especially because it has been found that repeated O2 can improve symptoms of depression [34]. However, N 2 O is considered a glutamate antagonist, unlike O2, which is highly concentrated in ACC and changes in the connectivity in this brain region may be more likely due to N 2 O.…”

Section: Discussionmentioning

confidence: 99%

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study

Desmidt,

Dujardin,

Andersson

et al. 2023

Mol Psychiatry

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Nitrous oxide (N 2 O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP).Thirty participants (20 depressed and 10 healthy controls -HC) were exposed to a one-hour single session of EMONO and followed for one week. Cerebral connectivity of the Anterior Cingulate Cortex (ACC, seed based resting state blood oxygen level dependent) and BTP (as assessed with ultrasound Tissue Pulsatility Imaging) were compared before and after exposure (as well as during exposure for BTP) among HC, non-responders and responders. Response was de ned as a reduction of at least 50% in the MADRS score one week after exposure. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a signi cant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also signi cantly decreased after exposure in HC and in non-responders. BTP signi cantly increased in the 3 groups between baseline and gas exposure, but the increase in BTP within the rst ten minutes was only signi cant in responders.We found that a single session of EMONO can rapidly modify the functional connectivity in the ACC, especially in the subgenual region, which appears to contribute to the antidepressant response. In addition, larger increases in BTP, associated with a signi cant rise in cerebral blood ow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identi ed potential cerebral mechanisms related to the antidepressant response of N 2 O, as well as potential markers for treatment response with this fast-acting antidepressant.

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“…In addition, it is increasingly used for preconditioning (even in combination with hypoxia) during sports training, for cardiovascular conditioning, or before extreme environmental stress, such as SCUBA diving, military free-fall or space flight, to reduce the chance of decompression sickness ( Webb and Pilmanis, 2011 ; Balestra et al, 2021 ; Lafère et al, 2021 ; Bestavashvili et al, 2022 ). Furthermore, many researchers point to the potential therapeutic application of oxygen therapy for depression or age-related neurological diseases such as Alzheimer’s disease ( Serebrovska et al, 2019 ; Bloch et al, 2021 ). One potential application of a hyperoxic environment has also been proposed even in an extraterrestrial application providing a slight increase in the partial pressure of O 2 on the Moon in underground tunnels to supply O 2 and compensate for the total pressure ( Martin and Benaroya, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Short-term hyperoxia-induced functional and morphological changes in rat hippocampus

Hencz,

Magony,

Thomas

et al. 2024

Front. Cell. Neurosci.

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Excess oxygen (O2) levels may have a stimulating effect, but in the long term, and at high concentrations of O2, it is harmful to the nervous system. The hippocampus is very sensitive to pathophysiological changes and altered O2 concentrations can interfere with hippocampus-dependent learning and memory functions. In this study, we investigated the hyperoxia-induced changes in the rat hippocampus to evaluate the short-term effect of mild and severe hyperoxia. Wistar male rats were randomly divided into control (21% O2), mild hyperoxia (30% O2), and severe hyperoxia groups (100% O2). The O2 exposure lasted for 60 min. Multi-channel silicon probes were used to study network oscillations and firing properties of hippocampal putative inhibitory and excitatory neurons. Neural damage was assessed using the Gallyas silver impregnation method. Mild hyperoxia (30% O2) led to the formation of moderate numbers of silver-impregnated “dark” neurons in the hippocampus. On the other hand, exposure to 100% O2 was associated with a significant increase in the number of “dark” neurons located mostly in the hilus. The peak frequency of the delta oscillation decreased significantly in both mild and severe hyperoxia in urethane anesthetized rats. Compared to normoxia, the firing activity of pyramidal neurons under hyperoxia increased while it was more heterogeneous in putative interneurons in the cornu ammonis area 1 (CA1) and area 3 (CA3). These results indicate that short-term hyperoxia can change the firing properties of hippocampal neurons and network oscillations and damage neurons. Therefore, the use of elevated O2 concentration inhalation in hospitals (i.e., COVID treatment and surgery) and in various non-medical scenarios (i.e., airplane emergency O2 masks, fire-fighters, and high altitude trekkers) must be used with extreme caution.

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Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial

Cited by 6 publications

References 81 publications

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study

Short-term hyperoxia-induced functional and morphological changes in rat hippocampus

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