ADHD

Research & Studies

Oxidative stress and ADHD: A meta-analysis

 

“They suggest that patients with ADHD have normal levels of antioxidant production, but that their response to oxidative stress is insufficient, leading to oxidative damage.”

 

Joseph, N., Zhang-James, Y., Perl, A., & Faraone, S. V. (2013). Oxidative stress and ADHD: A meta-analysis. Journal of Attention Disorders, 19(11), 915-924. doi: 10.1177/1087054713510354

 

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

 

Increased oxidative stress in children with attention deficit hyperactivity disorder

 

“The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD). We found decreased PON-1, ARE activity and total antioxidant status, and increased total oxidant status and oxidative stress index in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.”

 

Sezen, H., Kandemir, H., Savik, E., Kandemir, S. B., Kilicaslan, F., Bilinc, H., & Aksoy, N. (2016). Increased oxidative stress in children with attention deficit hyperactivity disorder. Redox Report, 21(6), 248-253. doi: 10.1080/13510002.2015.1116729

 

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  

 

Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder

 

“The present study evaluated oxidative balance in pediatric and adolescent patients with attention deficit hyperactivity disorder (ADHD). Our findings demonstrated that oxidative balance is impaired and oxidative stress is increased in children and adolescents with ADHD. This results are consistent with those of previous studies.”

 

Kul, M., Unal, F., Kandemir, H., Sarkarati, B., Kilinc, K., & Kandemir, S. B. (2015). Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder. Psychiatry Investigation, 12(3), 361-366. doi: 10.4306/pi.2015.12.3.361

 

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  

 

Attention deficit hyperactivity disorder and oxidative stress: A short term follow up study

 

“Oxidative metabolism was found to be impaired in children and adolescents with ADHD. It was also determined that methylphenidate repairs the oxidative balance by increasing antioxidant defense mechanisms.”

 

Guney, E., Cetin, F. H., Alisik, M., Tunca, H., Torun, Y. T., Iseri, E., . . . Erel, O. (2015). Attention deficit hyperactivity disorder and oxidative stress: A short term follow up study. Psychiatry Research, 229(1-2), 310-317. doi: 10.1016/j.psychres.2015.07.003

 

A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

 

Increased oxidative stress in children with attention deficit hyperactivity disorder

 

“The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD). We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.”

 

Sezen, H., Kandemir, H., Savik, E., Kandemir, S. B., Kilicaslan, F., Bilinc, H., & Aksoy, N. (2016). Increased oxidative stress in children with attention deficit hyperactivity disorder. Redox Report, 21(6), 248-253. doi: 10.1080/13510002.2015.1116729

 

Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice

 

“Continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.”

 

Nagata, K., Nakashima-Kamimura, N., Mikami, T., Ohsawa, I., & Ohta, S. (2008). Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology, 34(2), 501-508. doi: 10.1038/npp.2008.95

 

Malondialdehyde (oxidative marker) levels in adult attention-deficit hyperactivity disorder

 

“This is the first study evaluating oxidative metabolism in A-ADHD. Our findings that the mean plasma MDA levels of patients having A-ADHD were significantly higher than those of the control group and that MDA levels were correlated with the number of criteria met for hyperactivity and with the total score for hyperactivity/impulsivity in the A-ADHD patients may provide a guide for further clinical enzymologic and biochemical studies on A-ADHD.”

 

Bulut, M., Selek, S., Gergerlioglu, H. S., Savas, H. A., Yilmaz, H. R., Yuce, M., & Ekici, G. (2007). Malondialdehyde levels in adult attention-deficit hyperactivity disorder. Journal of Psychiatry Neuroscience, 32(6), 435-438. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077350/

 

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

 

Evaluating dopamine reward pathway in ADHD  

 

“In conclusion, these findings show a reduction in dopamine synaptic markers in the dopamine reward pathway midbrain and accumbens region of participants with ADHD that were associated with measures of attention. It also provides preliminary evidence of hypothalamic involvement in ADHD (lower than normal D2/D3 receptor availability).”

 

Volkow, N. D., Wang, G., Kollins, S. H., Wigal, T. L., Newcorn, J. H., Telang, F., . . . Swanson, J. M. (2009). Evaluating dopamine reward pathway in ADHD. Jama, 302(10), 1084-1091. doi: 10.1001/jama.2009.1308

 

Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease

 

“Methamphetamine-induced behavioral analysis showed that molecular hydrogen prevented both the development and progression of the nigrostrital degeneration. Tyrosine hydroxylase staining of the substantia nigra and striatum also demonstrated that pre- and post-treatment with hydrogen prevented the dopaminergic cell loss. Our studies suggest that hydrogen water is likely able to retard the development and progression of Parkinson's.”

 

Fu, Y., Ito, M., Fujita, Y., Ito, M., Ichihara, M., Masuda, A., . . . Ohno, K. (2009). Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease. Neuroscience Letters, 453(2), 81-85. doi: 10.1016/j.neulet.2009.02.016

 

Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder

 

“This study reveals depressed dopamine activity in caudate and preliminary evidence in limbic regions in adults with ADHD that was associated with inattention and with enhanced reinforcing responses to intravenous methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD.”

 

Volkow, N. D., Wang, G., Newcorn, J., Telang, F., Solanto, M. V., Fowler, J. S., . . . Swanson, J. M. (2007). Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 64(8), 932-940. doi: 10.1001/archpsyc.64.8.932

 

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

                                                                                                                                                                                                  

“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). Our results indicated that low concentration of H(2) in drinking water can reduce oxidative stress in the brain. Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.”

 

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

 

Oxidative and nitrosative stress in ADHD: Possible causes and the potential of antioxidant-targeted therapies

 

“In this article, research investigating O&NS in ADHD is reviewed and its impact on catecholaminergic activity and neurological structure is discussed. Lifestyle, environmental, psychological and nutritional influences on O&NS in people with ADHD are reviewed, and evidence for the therapeutic efficacy of antioxidant-related therapies is assessed.”

 

Lopresti, A. L. (2015). Oxidative and nitrosative stress in ADHD: Possible causes and the potential of antioxidant-targeted therapies. Attention Deficit and Hyperactivity Disorders, 7(4), 237-247. doi: 10.1007/s12402-015-0170-5

 

ROS and brain diseases: The good, the bad, and the ugly

 

“A common denominator of all neuropsychiatric diseases including schizophrenia and ADHD is an increased inflammatory response of the brain caused either by an exposure to proinflammatory agents during development or an accumulation of degenerated neurons, oxidized proteins, glycated products, or lipid peroxidation in the adult brain. Therefore, modulation of the prooxidant-antioxidant balance provides a therapeutic option which can be used to improve neuroprotection in response to oxidative stress. We also discuss the neuroprotective role of the nuclear factor erythroid 2-related factor (Nrf2) in the aged brain in response to oxidative stressors and nanoparticle-mediated delivery of ROS-scavenging drugs.” 

 

Popa-Wagner, A., Mitran, S., Sivanesan, S., Chang, E., & Buga, A.M. (2013). ROS and brain diseases: The good, the bad, and the ugly. Oxidative medicine and cellular longevity, 2013(963520), 1-14. doi: 10.1155/2013/963520

 

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. Moreover, H2 passes through the blood brain barrier, although most antioxidant compounds cannot; this is also an advantage of H2.”

 

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

 

Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction

 

“Since cybrids are shown to replicate mitochondrial defects seen in post-mortem brains, these observed defects in ADHD cybrids strongly suggest mitochondrial pathology in this disorder. Mitochondrial defects are detected in ADHD cybrids created from patients' platelets, implying bioenergetics crisis in the mitochondria could be a contributory factor for ADHD pathology and/or phenotypes.”

 

Verma, P., Singh, A., Nthenge-Ngumbau, D. N., Rajamma, U., Sinha, S., Mukhopadhyay, K., & Mohanakumar, K. P. (2016). Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction. BBA Clinical, 6(2016), 153-158. doi: 10.1016/j.bbacli.2016.10.003

 

Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

 

“Hydrogen-enriched water improves mitochondrial dysfunction in MM and inflammatory processes in PM/DM. Less prominent effects with the double-blind trial compared to the open-label trial were likely due to a lower amount of administered hydrogen and a shorter observation period, which implies a threshold effect or a dose-response effect of hydrogen.”

 

Ito, M., Ibi, T., Sahashi, K., Ichihara, M., Ito, M., & Ohno, K. (2011). Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research, 1(24), 1-8. doi: 10.1186/2045-9912-1-24

 

Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

 

“Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.”

 

Ohta, S. (2012). Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochimica et Biophysica Acta (BBA) - General Subjects, 1820(5), 586-594. doi: 10.1016/j.bbagen.2011.05.006

 

Hydrogen-rich saline attenuates neuronal ischemia-reperfusion injury by protecting mitochondrial function in rats.

 

“Hydrogen-rich saline treatment significantly improved the amount of surviving cells (P < 0.05). Furthermore, hydrogen-rich saline not only reduced tissue damage, the degree of mitochondrial swelling, and the loss of mitochondrial membrane potential but also preserved the mitochondrial cytochrome c content (P < 0.05). Our study showed that hydrogen-rich saline was able to attenuate neuronal I/R injury, probably by protecting mitochondrial function in rats.”

 

Cui, Y., Zhang, H., Ji, M., Jia, M., Chen, H., Yang, J., & Duan, M. (2014). Hydrogen-rich saline attenuates neuronal ischemia–reperfusion injury by protecting mitochondrial function in rats. Journal of Surgical Research, 192(2), 564-572. doi: 10.1016/j.jss.2014.05.060

 

Nutrition, immunological mechanisms and dietary immunomodulation in ADHD

 

“Attention-deficit hyperactivity disorder (ADHD) etiology is not completely understood, but common comorbid dysfunction of the gastrointestinal and immune system suggests that these systems may be affected by a common genetic background and molecular mechanisms. For example, increased levels of specific cytokines were observed in ADHD. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation. Modulation of immune system activity might have potential in ADHD treatment.”

 

Verlaet, A. A., Noriega, D. B., Hermans, N., & Savelkoul, H. F. (2014). Nutrition, immunological mechanisms and dietary immunomodulation in ADHD. European Child & Adolescent Psychiatry, 23(7), 519-529. doi: 10.1007/s00787-014-0522-2

 

Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease

 

“After Aβ1-42 injection, the level of IL-1β, 8-OH-dG, JNK and NF-κB all increased in brain tissues, while hydrogen-rich saline treatment decreased the level of IL-1β, 8-OH-dG and the activation of JNK and NF-κB. In conclusion, hydrogen-rich saline prevented Aβ-induced neuroinflammation and oxidative stress, possibly by attenuation of activation of c-Jun NH₂-terminal kinase (JNK) and nuclear factor-κB (NF-κB) in this rat model.”

 

Wang, C., Li, J., Liu, Q., Yang, R., Zhang, J. H., Cao, Y., & Sun, X. (2011). Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neuroscience Letters, 491(2), 127-132. doi: 10.1016/j.neulet.2011.01.022

 

Neurotrophins and neuronal plasticity

 

“There is increasing evidence that neurotrophins (NTs) are involved in processes of neuronal plasticity besides their well-established actions in regulating the survival, differentiation, and maintenance of functions of specific populations of neurons…It enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in mechanisms of neuronal plasticity, such as long-term potentiation and learning.”

Thoenen, H. (1995). Neurotrophins and neuronal plasticity. Science, 270(5236), 593-598. doi: 10.1126/science.270.5236.593

 

Molecular genetics of attention-deficit/hyperactivity disorder

 

“Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD.”

 

Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Skylar, P. (2005). Molecular genetics of attention deficit hyperactivity disorder. Biological Psychiatry, 57(11), 1313-1323. doi: 10.1016/j.biopsych.2004.11.024

 

Attention deficit hyperactivity disorder: Fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11

 

“Genome scan studies on potential alleles for ADHD have demonstrated linkage on chromosomes 5p13, 6q12, 16p13, 17p11 and 11q22-25.”

 

Ogdie, M. N., Fisher, S. E., Yang, M., Ishii, J., Francks, C., Loo, S. K., . . . Nelson, S. F. (2004). Attention deficit hyperactivity disorder: Fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11. The American Journal of Human Genetics, 75(4), 661–668. doi: 10.1086/424387

 

White-matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

 

“In 15 young males with ADHD, Silk et al. (2008) found WM abnormalities in several distinct regions underlying the inferior parietal, occipito-parietal, inferior frontal, and inferior temporal cortex.”

 

Silk, T. J., Vance, A., Rinehart, N., Bradshaw, J. L., & Cunnington, R. (2009). White-matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study. Human Brain Mapping, 30(9), 2757–2765. doi: 10.1002/hbm.20703

 

 

Attention and executive systems abnormalities in adults with childhood ADHD: A DT-MRI study of connections

 

“Recent magnetic resonance imaging (MRI) structural investigations have shown that white matter alterations are present in children, adolescents and adults with ADHD.”

 

Makris, N., Buka, S. L., Biederman, J., Papadimitriou, G. M., Hodge, S. M., Valera, E. M., . . . Seidman, L. J. (2008). Attention and executive systems abnormalities in adults with childhood ADHD: A DT-MRI study of connections. Cerebral Cortex, 18(5), 1210–1220. doi: 10.1093/cercor/bhm156

 

[Structural and functional neuroanatomy of attention-deficit hyperactivity disorder (ADHD)]

 

“Growing evidence points to the involvement of the frontostriatal network as a likely contributor to the pathophysiology of ADHD. This network involves the lateral prefrontal cortex, the dorsal anterior cingulate cortex, and the caudate nucleus and putamen. In ADHD patients, reductions in volume have been observed in total cerebral volume, the prefrontal cortex, the basal ganglia (striatum), the dorsal anterior cingulate cortex, the corpus callosum and the cerebellum.”

 

Emond, V., Joyal, C., & Poissant, H. (2009). [Structural and functional neuroanatomy of attention-deficit hyperactivity disorder (ADHD)]. L’ Encephale, 35(2), 107–114. doi: 10.1016/j.encep.2008.01.005

 

Brain development and ADHD

 

“Neuroimaging studies have also reported reduced white matter (WM) volumes in ADHD patients compared with controls.”

 

Krain, A. L., & Castellanos, F. X. (2006). Brain development and ADHD. Clinical Psychology Review, 26(4), 433–444. doi: 10.1016/j.cpr.2006.01.005

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