The interplay of hypoxic and mental stress: Implications for anxiety and depressive disorders.
Neuroscience and biobehavioral reviews
Adequate oxygen supply is essential for the human brain to meet its high energy demands. Therefore, elaborate molecular and systemic mechanism are in place to enable adaptation to low oxygen availability. Anxiety and depressive disorders are characterized by alterations in brain oxygen metabolism and of its components, such as mitochondria or hypoxia inducible factor (HIF)-pathways. Conversely, sensitivity and tolerance to hypoxia may depend on parameters of mental stress and the severity of anxiety and depressive disorders. Here we discuss relevant mechanisms of adaptations to hypoxia, as well as their involvement in mental stress and the etiopathogenesis of anxiety and depressive disorders. We suggest that mechanisms of adaptations to hypoxia (including metabolic responses, inflammation, and the activation of chemosensitive brain regions) modulate and are modulated by stress-related pathways and associated psychiatric diseases. While severe chronic hypoxia or dysfunctional hypoxia adaptations can contribute to the pathogenesis of anxiety and depressive disorders, harnessing controlled responses to hypoxia to increase cellular and psychological resilience emerges as a novel treatment strategy for these diseases.
10.1016/j.neubiorev.2022.104718
Elevating the level of hypoxia inducible factor may be a new potential target for the treatment of depression.
Kang Ilhyang,Kondo Douglas,Kim Jungyoon,Lyoo In Kyoon,Yurgelun-Todd Deborah,Hwang Jaeuk,Renshaw Perry F
Medical hypotheses
Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor that regulates gene expressions in response to decreased oxygen levels in the tissue, or hypoxia. HIF-1 exerts protective effects against hypoxia by mediating mitochondrial metabolism and consequently reducing oxidative stress. Recently, increased levels of oxidative stress and abnormal energy metabolism in the brain have been suggested to play essential roles in the pathogenesis of depression. Given that HIF-1 activates creatine metabolism and increases phosphocreatine levels in the intestinal epithelial cells, we assume that HIF-1 may induce similar processes in the brain. Elevated phosphocreatine levels in the brain, as measured by magnetic resonance spectroscopy, were associated with better treatment response to the antidepressants in individuals with depression. In addition, oral creatine supplements, which led to increased phosphocreatine levels in the brain, also enhanced the effects of antidepressants in individuals with depression. As such, we hypothesized that increasing the HIF-1, which potentially facilitates creatine metabolism in the brain, might be a new therapeutic target in depression. With this regard, we suggested that interventions to elevate the HIF-1 levels in the brain, including the intermittent hypoxia conditioning and hyperbaric oxygen therapy, might be considered as new additional treatments for depression.
10.1016/j.mehy.2020.110398
Rate of oxygen consumption in seasonal and non-seasonal depression.
Pinchasov Boris B,Grischin Oleg V,Putilov Arcady A
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
Most depressives suffer from weight loss, anorexia and insomnia, while for winter depressives the typical symptoms are weight gain, carbohydrate craving, overeating, oversleeping and extreme lack of energy. It is important to know whether winter depressives differ from most other depressives on measures of energy regulation. In wintertime, we evaluated the rate of oxygen consumption in relationship to neuro-vegetative depressive symptoms in 92 Siberian women. The seated subjects underwent oxyspirography in the mid-morning (1.5 hours after a standard breakfast). It was found that the oxygen consumption rate was similar in non-depressed women (n = 25) and depressed women with non-seasonal depression (n = 27). The comparatively lower values were obtained in women with winter depression (n = 40). This finding supports the suggestion that the behaviour disturbances typical for winter depression may represent a physiological feedback loop to energy conservation.
10.3109/15622970209150608
Prevalence of depressive symptoms and depression in patients with severe oxygen-dependent chronic obstructive pulmonary disease.
Lacasse Y,Rousseau L,Maltais F
Journal of cardiopulmonary rehabilitation
PURPOSE:To measure the prevalence rate of significant depressive symptoms and depression and examine their consequences on quality of life in patients with severe oxygen-dependent chronic obstructive pulmonary disease (COPD). METHODS:Between November 1997 and March 1998, the authors conducted a cross-sectional study among the COPD patients registered at the Quebec City area respiratory home care service. Depression and quality of life were assessed using the Geriatric Depression Scale and the Medical Outcome Survey--Short Form 36 (SF-36). RESULTS:109 patients (63 men; mean age: 71) with severe COPD (median FEV1: 34%) were surveyed. Of them, 105 were on long-term oxygen therapy (LTOT), which had been introduced (median) 19 months earlier. Sixty-two patients (57%; 95% Cl: 47-66) demonstrated significant depressive symptoms; in addition, 20 patients (18%; Cl: 12-27) were severely depressed. Only 6% of those patients who met the criteria for depression were taking an antidepressant drug. We found significant and moderate correlations between the scores obtained from the Geriatric Depression Scale and 7 of the 8 domains of the SF-36. CONCLUSION:Significant depressive symptoms and depression are highly prevalent in patients with severe COPD on LTOT. There is strong evidence that depression is under-recognized and under-treated in this group of patients.
10.1097/00008483-200103000-00004
Comparison Among Aerobic Exercise and Other Types of Interventions to Treat Depression: A Systematic Review.
de Souza Moura Antonio Marcos,Lamego Murilo Khede,Paes Flávia,Ferreira Rocha Nuno Barbosa,Simoes-Silva Vitor,Rocha Susana Almeida,de Sá Filho Alberto Souza,Rimes Ridson,Manochio João,Budde Henning,Wegner Mirko,Mura Gioia,Arias-Carrión Oscar,Yuan Ti-Fei,Nardi Antonio Egidio,Machado Sergio
CNS & neurological disorders drug targets
Depression is a common and disabling disease that affects over 100 million people worldwide and can have a significant impact on physical and mental health, reducing their quality of life. Thus, the aim of this article was to provide information on research results and key chains related to the therapeutic effects of chronic aerobic exercise compared with other types of interventions to treat depression, which may become a useful clinical application in a near future. Researches have shown the effectiveness of alternative treatments, such as physical exercise, minimizing high financial costs and minimizing side effects. In this review, the data analyzed allows us to claim that alternative therapies, such as exercise, are effective on controlling and reducing symptoms. 69.3% of the studies that investigated the antidepressant effects of exercise on depressive were significant, and the other 30.7% of the studies improved only in general physiological aspects, such as increased oxygen uptake, increased use of blood glucose and decreased body fat percentage, with no improvement on symptoms of depression. From the sample analyzed, 71.4% was composed of women, and regarding the severity of symptoms, 85% had mild to moderate depression and only 15% had moderate to severe depression. However, there is still disagreement regarding the effect of exercise compared to the use of antidepressants in symptomatology and cognitive function in depression, this suggests that there is no consensus on the correct intensity of aerobic exercise as to achieve the best dose-response, with intensities high to moderate or moderate to mild.
10.2174/1871527315666151111120714
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.
Molecular psychiatry
Nitrous oxide (NO) 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 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of NO, as well as potential markers for treatment response with this fast-acting antidepressant.
10.1038/s41380-023-02217-6
Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species.
Wei Jianyang,Zhang Ming,Zhou Jie
Psychiatry research
Major depression is closely associated with immune dysregulation. Myeloid-derived suppressor cells (MDSCs) are an important suppressor of immune responses. The aim of this study was to evaluate the possible role of MDSCs in major depression patients. We collected peripheral blood mononuclear cells (PBMCs) from 25 major depression patients and 25 healthy donors, and the frequency of MDSCs was determined by flow cytometric analysis. The proportion of MDSCs was increased in the peripheral blood of major depression patients, when compared with healthy controls. Further functional studies revealed that MDSCs from depression patients suppressed T cell function potently. We examined the reactive oxygen species (ROS) content in MDSCs from 6 major depression patients and 6 healthy controls. The ROS content in depression derived MDSCs was significantly elevated, when compared with those from healthy controls. We also examined the arginase activity and NO content in 5 major depression patients and 5 healthy controls, respectively. But no significant changes were detected between two groups. Administration of a ROS inhibitor completely abrogated the suppressive effect of MDSCs on T cells. In conclusion, our study revealed that MDSCs from depression patients suppress T cell reponses in ROS-dependent manner.
10.1016/j.psychres.2015.06.002
Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology.
Gnaiger Erich
Advances in experimental medicine and biology
Oxygen pressure declines from normoxic air-level to the microenvironment of mitochondria where cytochrome c oxidase (COX) reduces oxygen to water at oxygen levels as low as 0.3 kPa (2 Torr; 3 microM; 1.5 % air saturation). Intracellular hypoxia is defined as (1) local oxygen pressure below normoxic reference states, or (2) limitation of mitochondrial respiration by oxygen levels below kinetic saturation, resulting in oxyconformance. High-resolution respirometry provides the methodology to measure mitochondrial and cellular oxygen kinetics in the relevant low oxygen range < 1 kPa (7.5 mmHg; 9-10 microM; 5% air saturation). Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 microM) in ADP-stimulated state 3. Thus mitochondrial respiration proceeds at 90% of its hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small but significant oxygen limitation even under normoxia in active muscle. Any impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a shift of mitochondrial oxygen kinetics to the right, particularly by competitive inhibition of COX by NO, causes a further depression of respiration and a compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen uptake increases above hyperbolic saturation, which is probably due to oxygen radical production rather than the kinetics of COX. In cultured cells, the pronounced oxygen uptake above mitochondrial saturation at air-level oxygen pressure cannot be inhibited by rotenone and antimycin A, amounting to > 20 % of routine respiration in fibroblasts. Biochemical models of oxyconformance of COX are evaluated relative to patterns of intracellular oxygen distribution in the tissue and enzyme turnover in vivo, considering the kinetic effects of COX excess capacity on flux through the mitochondrial electron transport chain.
10.1007/978-1-4419-8997-0_4
Markers of Oxidative Stress and Neuroprogression in Depression Disorder.
Vaváková Magdaléna,Ďuračková Zdeňka,Trebatická Jana
Oxidative medicine and cellular longevity
Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.
10.1155/2015/898393
[The effect of reduced oxygen saturation during sleep on depression].
Szabó Krisztina,Ihász Ferenc
Orvosi hetilap
Numerous data suggest that episodes of breathing disorder during sleep are closely related to chronic cardiovascular and mental illnesses. In this study, we sought to find out how the decrease in oxygen saturation level and its duration during sleep are affected by the degree of depression and its extent. Data of 76 persons were processed in the study. The oxygen saturation measured during sleep was obtained from data from a polysomnographic filter device. Data collection for depression symptoms was done with a validated questionnaire. The decrease of night oxygen saturation on the effect of the disease was illustrated by the odds ratio calculation. The value below 90% of the average oxygen saturation during sleep time will more than double the risk of developing depression. It is also a risk factor for the severity of depression. Examining the duration of sleep time at reduced saturation, it mainly increases the chance of severe depression. Hypoxia during sleep and duration of hypoxic periods are a risk factor for the development of depression with therapeutic and diagnostic consequences. Orv Hetil. 2019; 160(20): 780-783.
10.1556/650.2019.31401
Depression accelerates the development of gastric cancer through reactive oxygen species‑activated ABL1 (Review).
Huang Tianhe,Zhou Fuling,Wang-Johanning Feng,Nan Kejun,Wei Yongchang
Oncology reports
Depression is a common symptom among gastric cancer (GC) patients and serves as a potential indication of poor prognosis and advanced cancer clinical stage. However, the molecular mechanism of depression‑associated poor prognoses of GC patients remains unclear. Recent studies have revealed that GC patients with depression are under high levels of oxidative stress (OS) status that is accompanied by the dysfunction of numerous proto‑oncogenes, including the ABL proto‑oncogene 1 (ABL1), which is a non‑receptor tyrosine kinase. Recent evidence indicates that ABL1 was dysregulated in both major depressive disorder (MDD) and cancer patients with depression, and high levels of reactive oxygen species (ROS) can lead to the activation of ABL1 in response to OS and that activated ABL1 subsequently contributes to development of GC via interactions with the downstream targets and corresponding signaling pathways. In this review, we examine the evidence to illuminate the molecular mechanism of ABL1 in the progression of GC patients with depression and identify out new and effective methods for the initial and long‑term treatment of GC.
10.3892/or.2016.5127
Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial.
Scientific reports
Oxygen enriched air may increase oxygen pressure in brain tissue and have biochemical effects even in subjects without lung disease. Consistently, several studies demonstrated that normobaric oxygen treatment has clinical benefits in some neurological conditions. This study examined the efficacy of normobaric oxygen treatment in subjects with depression. In a randomized, double-blind trial, 55 participants aged 18-65 years with mild to moderate depression (had a Hamilton Rating Scale for Depression [HRSD] score of ≥ 8) were recruited to the study from the Southern district in Israel. Participants underwent a psychiatric inclusion assessment at baseline and then were randomly assigned to either normobaric oxygen treatment of 35% fraction of inspired oxygen or 21% fraction of inspired oxygen (room air) through a nasal tube, for 4 weeks, during the night. Evaluations were performed at baseline, 2 and 4 weeks after commencement of study interventions, using the following tools: HRSD; Clinical Global Impression (CGI) questionnaire; World Health Organization-5 questionnaire for the estimation of Quality of Life (WHO-5-QOL); Sense of Coherence (SOC) 13-item questionnaire; and, Sheehan Disability Scale (SDS). A multivariate regression analysis showed that the mean ± standard deviation [SD] changes in the HRSD scores from baseline to week four were - 4.2 ± 0.3 points in the oxygen-treated group and - 0.7 ± 0.6 in the control group, for a between-group difference of 3.5 points (95% confidence interval [CI] - 5.95 to - 1.0; P = 0.007). Similarly, at week four there was a between-group difference of 0.71 points in the CGI score (95% CI - 1.00 to - 0.29; P = 0.001). On the other hand, the analysis revealed that there were no significant differences in WHO-5-QOL, SOC-13 or SDS scores between the groups. This study showed a significant beneficial effect of oxygen treatment on some symptoms of depression.Trial registration: NCT02149563 (29/05/2014).
10.1038/s41598-021-98245-9
Role of oxidative stress in depression.
Bhatt Shvetank,Nagappa Anantha Naik,Patil Chandragouda R
Drug discovery today
Reactive oxygen species (ROS) have vital roles in cellular signaling and in defence against invasive microorganisms. Excessive ROS generation and exhaustion of antioxidative defences trigger proinflammatory signaling, damaging vital macromolecules and inducing cellular apoptosis. The failure of cells to maintain redox homeostasis and resultant generation of proinflammatory mediators leads to cell necrosis. The brain is more vulnerable to oxidative stress (OS) because of its higher oxygen consumption, higher lipid content, and weaker antioxidative defence. OS is a main cause of neurodegeneration and its involvement in the pathogenesis of major depressive disorder (MDD) is unequivocally established. OS and proinflammatory signaling have emerged as mainstays in the pathogenesis of MDD. Targeting these changes with suitable antioxidants could be an effective strategy to treat MDD.
10.1016/j.drudis.2020.05.001