Depression Prevention and Recovery Program
Research & Studies

Oxidative stress and major depression

 

“The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression.”

 

Bajpai, A., Verma, A. K., Srivastava, M., & Srivastava, R. (2014). Oxidative stress and major depression. Journal Of Clinical and Diagnostic Research, 8(12), 04-07. doi: 10.7860/jcdr/2014/10258.5292

 

Effects of hydrogen-rich water on depressive-like behavior in mice

 

“Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.”

 

Zhang, Y., Su, W., Chen, Y., Wu, T., Gong, H., Shen, X., . . . Jiang, C. (2016). Effects of hydrogen-rich water on depressive-like behavior in mice. Scientific Reports, 6(23742), 1-7. doi: 10.1038/srep23742 

 

Depression and oxidative stress: Results from a meta-analysis of observational studies

 

“This meta-analysis observed an association between depression and oxidative stress and antioxidant status across many different studies. Differences in measures of depression and markers of oxidative stress and antioxidant status markers could account for the observed heterogeneity. These findings suggest that well-established associations between depression and poor health outcomes may be mediated by high oxidative stress.”

 

Palta, P., Samuel, L. J., Miller, E. R., & Szanton, S. L. (2014). Depression and oxidative stress: Results from a meta-analysis of observational studies. Psychosomatic Medicine, 76(1), 12-19. doi: 10.1097/psy.0000000000000009

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications

 

“H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations as well.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Novel therapeutic targets in depression and anxiety: Antioxidants as a candidate treatment

 

“There is growing evidence that the imbalance between oxidative stress and the antioxidant defense system may be associated with the development neuropsychiatric disorders, such as depression and anxiety. Major depression and anxiety are presently correlated with a lowered total antioxidant state and by an activated oxidative stress (OS) pathway.”

 

Xu, Y., Wang, C., Klabnik, J. J., & O'Donnell, J. M. (2014). Novel therapeutic targets in depression and anxiety: Antioxidants as a candidate treatment. Current Neuropharmocalogy, 12(2), 108-119. doi: 10.2174/1570159X11666131120231448

 

 

The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

Review: The role of inflammation in depression

 

“The role of inflammation in major depressive disorder (MDD) has been of growing interest over the past two decades and evidence suggests it plays a role in depression. Cytokines have been found to influence almost every pathway involved in the pathogenesis of depression including alterations to the expression of neurotransmitters, neuroendocrine function, synaptic plasticity and basal ganglia.”

 

Patel, A. (2013). Review: The role of inflammation in depression. Psychiatria Danubina, 25(2), 216-223. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23995180

 

​Hydrogen as a selective antioxidant: A review of clinical and experimental studies

 ​

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

A meta-analysis of oxidative stress markers in depression

 

“Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients.”

 

Liu, T., Zhong, S., Liao, X., Chen, J., He, T., Lai, S., & Jia, Y. (2015). A meta-analysis of oxidative stress markers in depression. PLOS ONE, 10(10), 1-17. doi: 10.1371/journal.pone.0138904

 

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Depression and oxidative stress: Results from a meta-analysis of observational studies

 

“These findings suggest that well-established associations between depression and poor health outcomes may be mediated by high oxidative stress.”

 

Palta, P., Samuel, L., Miller, E., & Szanton, S. (2013, December 12). Depression and oxidative stress: Results from a meta-analysis of observational studies. Psychosomatic Medicine, 76(1), 12-19. doi: 10.1097/PSY.0000000000000009

 

​Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

From inflammation to sickness and depression: When the immune system subjugates the brain

 

“Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.”

 

Dantzer, R., O'Connor, J., Freund, G., Johnson, R., & Kelley, K. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 45-46. doi: 10.1038/nrn2297

 

​Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine

 

“The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism.”

 

Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacology & Therapeutics, 144(1), 1-11. doi: 10.1016/j.pharmthera.2014.04.006

 

A meta-analysis of cytokines in major depression

 

“This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.”

 

Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E., & Lanctot, K. (20010, March 1). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446-57. doi: 10.1016/j.biopsych.2009.09.033

 

​Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats

 

“HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.”

 

Tian, R., Hou, Z., Hao, S., Wu, W., Mao, X., Tao, X., . . . Liu, B. (2016). Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats. Brain Research, 1637, 1-13. doi: 10.1016/j.brainres.2016.01.029

 

Inflammation in depression: Is adiposity a cause?

 

“Mounting evidence indicates that inflammation may play a significant role in the development of depression. Patients with depression exhibit increased inflammatory markers, and administration of cytokines and other inflammatory stimuli can induce depressive symptoms.”

 

Shelton, R., & Miller, A. (2011). Inflammation in depression: Is adiposity a cause? Dialogues in Clinical Neuroscience, 13(1), 41-53. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21485745

 

Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice

 

“We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation.”

 

Spulber, S., Edoff, K., Hong, L., Morisawa, S., Shirahata, S., & Ceccatelli, S. (2012). Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLOS ONE, 7(7), 1-12. doi: 10.1371/journal.pone.0042078

 

Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications

 

“Converging lines of evidence implicate the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depression. The meta-analysis revealed strong evidence that BDNF levels were lower in depressed subjects than healthy control subjects.”

 

Sen, S., Duman, R., & Sanacora, G. (2008). Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications. Biological Psychiatry, 64(6), 527-532. doi: 10.1016/j.biopsych.2008.05.005

 

Hydrogen-rich saline protects against spinal cord injury in rats

 

“Administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of Brain derived neurotrophic factor.”

 

Chen, C., Chen, Q., Mao, Y., Xu, S., Xia, C., Shi, X., . . . Sun, X. (2010). Hydrogen-rich saline protects against spinal cord injury in rats. Neurochemical Research, 35(7), 1111-1118. doi: 10.1007/s11064-010-0162-y

 

Brain-derived neurotrophic factor in mood disorders and antidepressant treatments

 

“Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment.”

 

Castrén, E., & Kojima, M. (2016). Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiology of Disease, 97(B), 119-126. doi: 10.1016/j.nbd.2016.07.010

 

Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury

 

“The benefits of hydrogen-rich saline are not limited to the kidney; it also reduces acute spinal cord contusion injury, possibly by decreasing oxidative stress, inflammation and apoptosis while increasing brain-derived neurotrophic factor expression and activation of the mitochondrial adenosine triphosphate-dependent potassium (mitoK ATP ) channel.”

 

Zhang, K., Wang, J., Zhang, Q., Zhu, K., Sun, J., Zhang, Z., & Sun, J. (2015). Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury. Neural Regeneration Research, 10(6), 958-964. doi: 10.4103/1673-5374.158361

 

Involvement of brain-derived neurotrophic factor in late-life depression

 

“Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease.”

 

Dwivedi, Y. (2013). Involvement of brain-derived neurotrophic factor in late-life depression. The American Journal of Geriatric Psychiatry, 21(5), 433-449. doi: 10.1016/j.jagp.2012.10.026

​Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury

 

“Treatment with hydrogen-rich saline, which elevated the levels of molecules associated with brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity, improved cognitive performance.”

 

Hou, Z., Luo, W., Sun, X., Hao, S., Zhang, Y., Xu, F., . . . Liu, B. (2012). Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Research Bulletin, 88(6), 560-565. doi: 10.1016/j.brainresbull.2012.06.006

 

Brain-derived neurotrophic factor: Role in depression and suicide

 

“Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior.”

 

Yogesh, D. (2009). Brain-derived neurotrophic factor: Role in depression and suicide. Neuropsychiatric Disease and Treatment, 5, 433-449. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732010/

 

Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats

 

“Hydrogen-rich saline reduced oxidative stress, increased antioxidant enzyme activities and preserved synaptophysin and brain derived neurotrophic factor levels in the diabetic rat retina.”

 

Feng, Y., Wang, R., Xu, J., Sun, J., Xu, T., Gu, Q., & Wu, X. (2012). Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Current Eye Research, 38(3), 396-404. doi: 10.3109/02713683.2012.748919

 

The role of dopamine in the pathophysiology of depression

 

“Multiple sources of evidence support a role for diminished dopaminergic neurotransmission in major depression. The physiological alterations underlying reduced dopamine (DA) signaling could result from either diminished DA release from presynaptic neurons or impaired signal transduction, either due to changes in receptor number or function and/or altered intracellular signal processing.”

 

Dunlop, B. W., & Nemeroff, C. B. (2007). The role of dopamine in the pathophysiology of depression. Archives of General Psychiatry, 64(3), 327-337. doi: 10.1001/archpsyc.64.3.327

 

 

Therapeutic effects of hydrogen in animal models of Parkinson's disease

 

“Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.”

 

Fujita, K., Nakabeppu, Y., & Noda, M. (2011). Therapeutic effects of hydrogen in animal models of Parkinson's disease. Parkinson's disease, 2011(307875), 1-9. doi: 10.4061/2011/307875

Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

 

“The dopamine system is unique among the brain's modulatory systems in that it has discrete projections to specific brain regions involved in motor behaviour, cognition and emotion. Dopamine neurons exhibit several activity patterns - including tonic and phasic firing - that are determined by a combination of endogenous pacemaker conductances and regulation by multiple afferent systems. Emerging evidence suggests that disruptions in these regulatory systems may underlie the pathophysiology of several psychiatric disorders, including schizophrenia and depression.”

 

Grace, A. A. (2016). Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nature Reviews Neuroscience, 17(8), 524-532. doi: 10.1038/nrn.2016.57

 

Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

 

“Here, we show that drinking H(2)-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

 

Fujita, K., Seike, T., Yutsudo, N., Ohno, M., Yamada, H., Yamaguchi, H., . . . Noda, M. (2009). Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PLOS ONE, 4(9). 1-10. doi: 10.1371/journal.pone.0007247

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