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Depression and Anxiety treatment with Vitamin D - probable molecular pathways - June 2022

Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety

Int. J. Mol. Sci. 2022, 23, 7077. https://doi.org/10.3390/ijms23137077
Bruna R. Kouba 1, Anderson Camargo 1 , Joana Gil-Mohapel 2,3,* and Ana Lucia S. Rodrigues h*
Citation: Kouba, B.R.; Camargo, A.; Gil-Mohapel, J.; Rodrigues, A.L.S. .
Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florianopolis 88040-900, SC, Brazil; rkba.bruna at gmail.com (B.R.K.); camargo.andersonc at gmail.com (A.C.)
Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada
Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
Correspondence: jgil at uvic.ca (J.G.-M.); ana.l.rodrigues at ufsc.br (A.L.S.R.); Tel.: +1-250-721-6586 (J.G.-M.); +55-(48)-3721-5043 (A.L.S.R.)

Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium-phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.
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From PDF: Clinical Studies: Effects of Vitamin D in Depression and Anxiety

Several studies have reported that vitamin D supplementation improves symptoms of depression and anxiety associated with various medical conditions, including type II diabetes, Crohn's disease, ulcerative colitis, and obesity [101-105].
However, the potential therapeutic effects of vitamin D in individuals primarily diagnosed with depression or anxiety remain controversial.
For example, vitamin D supplementation (1600IU for 6 months) was shown to significantly improve anxiety symptoms, but not depressive symptoms, in patients with vitamin D deficiency [106].
Likewise, supplementation with 2800 IU of vitamin D in patients with depression did not promote a significant reduction in Hamilton D-17 scores [107].
On the other hand, supplementation with 50,000 IU of vitamin D for 2 weeks was able to improve depression severity, as assessed with the Beck Depression Inventory-II (BDI-II), although no changes in serotonin levels were detected [108].
However, in another study, cholecalciferol treatment (50,000 IU for 3 months) significantly increased serum serotonin levels, while decreasing BDI scores in women with moderate, severe, and extreme depression.
Interestingly, among men, an improvement in the severity of depressive symptoms with vitamin D supplementation was only observed in those diagnosed with severe depression [83].
Beneficial effects of vitamin D (50,000 IU for 8 weeks) supplementation have also been observed in older adults (over 60 years of age) with depression [109]. However, lower doses of vitamin D (400 IU daily for 2 years) were not able to improve depressive symptoms [110].
Finally, a single dose of vitamin D (300,000 IU) was reported as an effective and safe intervention in MDD with concurrent vitamin D deficiency [111,112]. In patients with depression, the daily administration of 1500 IU vitamin D3 plus 20 mg fluoxetine for 8 weeks was superior to fluoxetine alone [113].
Another study reported that vitamin D supplementation (50,000 IU once/week for 3 months) in combination with standard of care improved the severity of anxiety in individuals diagnosed with Generalized Anxiety Disorder by increasing serotonin concentrations and decreasing the levels of the inflammatory biomarker neopterin [114].
Overall, although there is compelling clinical evidence pointing to the benefits of vitamin D for the management of depression and anxiety, it is important to note that divergent results have also been obtained [46].
Multiple factors may contribute to these discrepant results, including

  • differences in the doses of vitamin D used,
  • treatment time,
  • serum 25-hydroxyvitamin D levels at baseline,
  • nutritional condition at the onset of the treatment,
  • age and sex of the individuals,
  • as well as the presence of comorbidities that may influence the efficacy of vitamin D supplementation. Additionally, the heterogeneity observed in clinical studies may also be associated with genetic polymorphisms that may affect vitamin D efficacy [115-117].
From PDF Conclusions and Future Directions

In this review, we discussed the main evidence underlining the therapeutic potential of vitamin D in the management of depression and anxiety disorders. Of particular relevance, compelling evidence suggests that vitamin D possesses

  • antioxidant,
  • anti-inflammatory,
  • pro-neurogenic, and
  • neuromodulatory properties,

and, thus, may act in a similar manner to classic antidepressants. In support, several preclinical studies have shown the beneficial effects of vitamin D supplementation in animal models of these mood disorders. Given this, some studies have investigated the possible synergistic or additive beneficial effects of vitamin D and current pharmacotherapy for the management of anxiety and depression. However, the clinical studies that assess the efficacy of vitamin D supplementation in the treatment of depression and anxiety are still scarce and their results are, at times, controversial. The discrepant results from clinical trials call for the need to conduct future studies, so as to establish a protocol for vitamin D supplementation that is effective in preventing or attenuating depressive and anxiety symptoms. Therefore, appropriately randomized clinical trials assessing the potential of vitamin D as co-adjuvant for the treatment of these mood disorders are warranted, so as to ascertain the true therapeutic value of this vitamin in the context of depression and anxiety.

  1. Craske, M.G.; Stein, M.B.; Eley, T.C.; Milad, M.R.; Holmes, A.; Rapee, R.M.; Wittchen, H.U. Anxiety Disorders. Nat. Rev. Dis. Primers 2017, 3,17024. [CrossRef] [PubMed]
  2. Otte, C.; Gold, S.M.; Penninx, B.W.; Pariante, C.M.; Etkin, A.; Fava, M.; Mohr, D.C.; Schatzberg, A.F. Major Depressive Disorder. Nat. Rev. Dis. Primers 2016, 2,16065. [CrossRef] [PubMed]
  3. Lamers, F.; Van Oppen, P.; Comijs, H.C.; Smit, J.H.; Spinhoven, P.; van Balkom, A.J.L.M.; Nolen, W.A.; Zitman, F.G.; Beekman, A.T.F.; Penninx, B.W.J.H. Comorbidity Patterns of Anxiety and Depressive Disorders in a Large Cohort Study: The Netherlands Study of Depression and Anxiety (NESDA). J. Clin. Psychiatry 2011, 72, 341-348. [CrossRef]
  4. Malhi, G.S.; Mann, J.J. Depression. Lancet 2018, 392, 2299-2312. [CrossRef]
  5. Schiele, M.A.; Domschke, K. Epigenetics at the Crossroads between Genes, Environment and Resilience in Anxiety Disorders: Epigenetics in Anxiety Disorders. Genes Brain Behav. 2018,17, e12423. [CrossRef]
  6. De Haan, P.; Klein, H.C.; 't Hart, B.A. Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for Innovative Therapy. Front. Psychiatry 2017, 8, 46. [CrossRef]
  7. Carlessi, A.S.; Borba, L.A.; Zugno, A.I.; Quevedo, J.; Réus, G.Z. Gut Microbiota-Brain Axis in Depression: The Role of Neuroinflammation. Eur. J. Neurosci. 2021, 53, 222-235. [CrossRef]
  8. Kim, Y.K.; Jeon, S.W. Neuroinflammation and the Immune-Kynurenine Pathway in Anxiety Disorders. Curr. Neuropharmacol. 2018,16, 574-582. [CrossRef]
  9. Stevens, B.R.; Goel, R.; Seungbum, K.; Richards, E.M.; Holbert, R.C.; Pepine, C.J.; Raizada, M.K. Increased Human Intestinal Barrier Permeability Plasma Biomarkers Zonulin and FABP2 Correlated with Plasma LPS and Altered Gut Microbiome in Anxiety or Depression. Gut 2018, 67,1555-1557. [CrossRef]
  10. Fedotova, J.; Zarembo, D.; Dragasek, J.; Caprnda, M.; Kruzliak, P.; Dudnichenko, T. Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced Anxiety-Like Behavior of Adult Female Rats. Folia Med. 2017,59,139-158. [CrossRef]
  11. Khairy, E.Y.; Attia, M.M. Protective Effects of Vitamin D on Neurophysiologic Alterations in Brain Aging: Role of Brain-Derived Neurotrophic Factor (BDNF). Nutr. Neurosci. 2021, 24, 650-659. [CrossRef] [PubMed]
  12. Lefebvre d'Hellencourt, C.; Montero-Menei, C.N.; Bernard, R.; Couez, D. Vitamin D3 Inhibits Proinflammatory Cytokines and Nitric Oxide Production by the EOC13 Microglial Cell Line. J. Neurosci. Res. 2003, 71, 575-582. [CrossRef] [PubMed]
  13. Morello, M.; Landel, V.; Lacassagne, E.; Baranger, K.; Annweiler, C.; Féron, F.; Millet, P. Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer's Disease. Mol. Neurobiol. 2018, 55, 6463-6479. [CrossRef] [PubMed]
  14. Yong, H.Y.F.; Rawji, K.S.; Ghorbani, S.; Xue, M.; Yong, V.W. The Benefits of Neuroinflammation for the Repair of the Injured Central Nervous System. Cell. Mol. Immunol. 2019,16,540-546. [CrossRef] [PubMed]
  15. Fullerton, J.N.; Gilroy, D.W. Resolution of Inflammation: A New Therapeutic Frontier. Nat. Rev. Drug Discov. 2016,15, 551-567. [CrossRef]
  16. Barton, G.M. A Calculated Response: Control of Inflammation by the Innate Immune System. J. Clin. Investig. 2008,118, 413-420. [CrossRef]
  17. Herman, F.J.; Pasinetti, G.M. Principles of Inflammasome Priming and Inhibition: Implications for Psychiatric Disorders. Brain. Behav. Immun. 2018, 73, 66-84. [CrossRef]
  18. Orihuela, R.; McPherson, C.A.; Harry, G.J. Microglial M1/M2 Polarization and Metabolic States: Microglia Bioenergetics with Acute Polarization. Br. J. Pharmacol. 2016,173, 649-665. [CrossRef]
  19. Rudzki, L.; Maes, M. The Microbiota-Gut-Immune-Glia (MGIG) Axis in Major Depression. Mol. Neurobiol. 2020, 57, 4269-4295. [CrossRef]
  20. Kelley, N.; Jeltema, D.; Duan, Y.; He, Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019, 20, 3328. [CrossRef]
  21. Song, N.; Li, T. Regulation of NLRP3 Inflammasome by Phosphorylation. Front. Immunol. 2018, 9, 2305. [CrossRef] [PubMed]
  22. Liu, X.; Zhang, X.; Ding, Y.; Zhou, W.; Tao, L.; Lu, P.; Wang, Y.; Hu, R. Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming. Antioxid. Redox Signal. 2017, 26, 28-43. [CrossRef] [PubMed]
  23. Xu, X.; Zhang, L.; Ye, X.; Hao, Q.; Zhang, T.; Cui, G.; Yu, M. Nrf2/ARE Pathway Inhibits ROS-Induced NLRP3 Inflammasome Activation in BV2 Cells after Cerebral Ischemia Reperfusion. Inflamm. Res. 2018, 67, 57-65. [CrossRef] [PubMed]
  24. Sutterwala, F.S.; Haasken, S.; Cassel, S.L. Mechanism of NLRP3 Inflammasome Activation. Ann. N. Y. Acad. Sci. 2014,1319, 82-95. [CrossRef]
  25. Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.S.; Peterson, T.C.; et al. Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia. Nature 2017, 541, 481-487. [CrossRef]
  26. Tejeda, G.; Díaz-Guerra, M. Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies. Int. J. Mol. Sci. 2017,18, 268. [CrossRef]
  27. Farina, C.; Aloisi, F.; Meinl, E. Astrocytes Are Active Players in Cerebral Innate Immunity. Trends Immunol. 2007, 28,138-145. [CrossRef]
  28. Troubat, R.; Barone, P.; Leman, S.; Desmidt, T.; Cressant, A.; Atanasova, B.; Brizard, B.; El Hage, W.; Surget, A.; Belzung, C.; et al. Neuroinflammation and Depression: A Review. Eur. J. Neurosci. 2021, 53,151-171. [CrossRef]
  29. Bansal, Y.; Singh, R.; Parhar, I.; Kuhad, A.; Soga, T. Quinolinic Acid and Nuclear Factor Erythroid 2-Related Factor 2 in Depression: Role in Neuroprogression. Front. Pharmacol. 2019,10, 452. [CrossRef]
  30. Braidy, N.; Grant, R.; Brew, B.J.; Adams, S.; Jayasena, T.; Guillemin, G.J. Effects of Kynurenine Pathway Metabolites on Intracellular NAD + Synthesis and Cell Death in Human Primary Astrocytes and Neurons. Int. J. Tryptophan Res. 2009,2, 61-69. [CrossRef]
  31. Pierozan, P.; Biasibetti, H.; Schmitz, F.; Ávila, H.; Parisi, M.M.; Barbe-Tuana, F.; Wyse, A.T.S.; Pessoa-Pureur, R. Quinolinic Acid Neurotoxicity: Differential Roles of Astrocytes and Microglia via FGF-2-Mediated Signaling in Redox-Linked Cytoskeletal Changes. Biochim. Biophys. Acta BBA-Mol. Cell Res. 2016,1863, 3001-3014. [CrossRef]
  32. Agus, A.; Planchais, J.; Sokol, H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe 2018, 23, 716-724. [CrossRef] [PubMed]
  33. Chen, L.M.; Bao, C.H.; Wu, Y.; Liang, S.H.; Wang, D.; Wu, L.Y.; Huang, Y.; Liu, H.R.; Wu, H.G. Tryptophan-Kynurenine Metabolism: A Link between the Gut and Brain for Depression in Inflammatory Bowel Disease. J. Neuroinflammation 2021,18,135. [CrossRef] [PubMed]
  34. Siopi, E.; Chevalier, G.; Katsimpardi, L.; Saha, S.; Bigot, M.; Moigneu, C.; Eberl, G.; Lledo, P.M. Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine. Cell Rep. 2020, 30, 3682-3690.e6. [CrossRef] [PubMed]
  35. Duman, R.S. Neuronal Damage and Protection in the Pathophysiology and Treatment of Psychiatric Illness: Stress and Depression. Dialogues Clin. Neurosci. 2009,11, 239-255. [CrossRef] [PubMed]
  36. Charoenngam, N.; Shirvani, A.; Holick, M.F. Vitamin D for Skeletal and Non-Skeletal Health: What We Should Know. J. Clin. Orthop. Trauma 2019,10,1082-1093. [CrossRef]
  37. Holick, M.F. Vitamin D: A D-Lightful Solution for Health. J. Investig. Med. 2011, 59, 872-880. [CrossRef]
  38. Holick, M.F. Vitamin D Deficiency. N. Engl. J. Med. 2007, 357, 266-281. [CrossRef]
  39. Zhu, J.; DeLuca, H.F. Vitamin D 25-Hydroxylase—Four Decades of Searching, Are We There Yet? Arch. Biochem. Biophys. 2012, 523, 30-36. [CrossRef]
  40. Hossein-nezhad, A.; Holick, M.F. Vitamin D for Health: A Global Perspective. Mayo Clin. Proc. 2013, 88, 720-755. [CrossRef]
  41. Christakos, S.; Dhawan, P.; Verstuyf, A.; Verlinden, L.; Carmeliet, G. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol. Rev. 2016, 96, 365-408. [CrossRef] [PubMed]
  42. Wacker, M.; Holick, M. Vitamin D—Effects on Skeletal and Extraskeletal Health and the Need for Supplementation. Nutrients 2013, 5,111-148. [CrossRef] [PubMed]
  43. Haussler, M.R.; Whitfield, G.K.; Kaneko, I.; Haussler, C.A.; Hsieh, D.; Hsieh, J.-C.; Jurutka, P.W. Molecular Mechanisms of Vitamin D Action. Calcif. Tissue Int. 2013, 92, 77-98. [CrossRef] [PubMed]
  44. Alshahrani, F.; Aljohani, N. Vitamin D: Deficiency, Sufficiency and Toxicity. Nutrients 2013, 5, 3605-3616. [CrossRef]
  45. Eyles, D.W.; Smith, S.; Kinobe, R.; Hewison, M.; McGrath, J.J. Distribution of the Vitamin D Receptor and 1 a-Hydroxylase in Human Brain. J. Chem. Neuroanat. 2005,29, 21-30. [CrossRef]
  46. Casseb, G.A.S.; Kaster, M.P.; Rodrigues, A.L.S. Potential Role of Vitamin D for the Management of Depression and Anxiety. CNS Drugs 2019, 33, 619-637. [CrossRef]
  47. Hoogendijk, W.J.G.; Lips, P.; Dik, M.G.; Deeg, D.J.H.; Beekman, A.T.F.; Penninx, B.W.J.H. Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults. Arch. Gen. Psychiatry 2008, 65, 508. [CrossRef]
  48. Pu, D.; Luo, J.; Wang, Y.; Ju, B.; Lv, X.; Fan, P.; He, L. Prevalence of Depression and Anxiety in Rheumatoid Arthritis Patients and Their Associations with Serum Vitamin D Level. Clin. Rheumatol. 2018, 37,179-184. [CrossRef]
  49. Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C. Vitamin D: Modulator of the Immune System. Curr. Opin. Pharmacol. 2010,10, 482-496. [CrossRef]
  50. Nakajo, T.; Katayoshi, T.; Kitajima, N.; Tsuji-Naito, K. 1,25-Dihydroxyvitamin D3 Attenuates IL-1 ß Secretion by Suppressing NLRP1 Inflammasome Activation by Upregulating the NRF2-HO-1 Pathway in Epidermal Keratinocytes. Redox Biol. 2021, 48, 102203. [CrossRef]
  51. Yamini, P.; Ray, R.S.; Chopra, K. Vitamin D3 Attenuates Cognitive Deficits and Neuroinflammatory Responses in ICV-STZ Induced Sporadic Alzheimer's Disease. Inflammopharmacology 2018, 26, 39-55. [CrossRef]
  52. Cui, C.; Xu, P.; Li, G.; Qiao, Y.; Han, W.; Geng, C.; Liao, D.; Yang, M.; Chen, D.; Jiang, P. Vitamin D Receptor Activation Regulates Microglia Polarization and Oxidative Stress in Spontaneously Hypertensive Rats and Angiotensin II-Exposed Microglial Cells: Role of Renin-Angiotensin System. Redox Biol. 2019, 26,101295. [CrossRef] [PubMed]
  53. Boontanrart, M.; Hall, S.D.; Spanier, J.A.; Hayes, C.E.; Olson, J.K. Vitamin D3 Alters Microglia Immune Activation by an IL-10 Dependent SOCS3 Mechanism. J. Neuroimmunol. 2016,292,126-136. [CrossRef] [PubMed]
  54. Calvello, R.; Cianciulli, A.; Nicolardi, G.; De Nuccio, F.; Giannotti, L.; Salvatore, R.; Porro, C.; Trotta, T.; Panaro, M.A.; Lofrumento, D.D. Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson's Disease, Shifting M1 to M2 Microglia Responses. J. Neuroimmune Pharmacol. 2017,12, 327-339. [CrossRef] [PubMed]
  55. Verma, R.; Jung, J.H.; Kim, J.Y. 1,25-Dihydroxyvitamin D3 up-Regulates TLR10 While down-Regulating TLR2, 4, and 5 in Human Monocyte THP-1. J. Steroid Biochem. Mol. Biol. 2014,141,1-6. [CrossRef]
  56. Verma, R.; Kim, J.Y. 1,25-Dihydroxyvitamin D3 Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells. Neuroimmunomodulation 2016, 23, 75-80. [CrossRef]
  57. Camargo, A.; Dalmagro, A.P.; Platt, N.; Rosado, A.F.; Neis, V.B.; Zeni, A.L.B.; Kaster, M.P.; Rodrigues, A.L.S. Cholecalciferol Abolishes Depressive-like Behavior and Hippocampal Glucocorticoid Receptor Impairment Induced by Chronic Corticosterone Administration in Mice. Pharmacol. Biochem. Behav. 2020,196,172971. [CrossRef]
  58. Xin, L.; Che, B.; Zhai, B.; Luo, Q.; Zhang, C.; Wang, J.; Wang, S.; Fan, G.; Liu, Z.; Feng, J.; et al. 1,25-Dihydroxy Vitamin D3 Attenuates the Oxidative Stress-Mediated Inflammation Induced by PM2.5via the P38/NF-KB/NLRP3 Pathway. Inflammation 2019, 42, 702-713. [CrossRef]
  59. Jiang, S.; Zhang, H.; Li, X.; Yi, B.; Huang, L.; Hu, Z.; Li, A.; Du, J.; Li, Y.; Zhang, W. Vitamin D/VDR Attenuate Cisplatin-Induced AKI by down-Regulating NLRP3/Caspase-1/GSDMD Pyroptosis Pathway. J. Steroid Biochem. Mol. Biol. 2021, 206,105789. [CrossRef]
  60. Cohen-Lahav, M.; Shany, S.; Tobvin, D.; Chaimovitz, C.; Douvdevani, A. Vitamin D Decreases NFkB Activity by Increasing IkBä Levels. Nephrol. Dial. Transplant. 2006, 21, 889-897. [CrossRef]
  61. Huang, H.; Hong, J.Y.; Wu, Y.J.; Wang, E.Y.; Liu, Z.Q.; Cheng, B.H.; Mei, L.; Liu, Z.G.; Yang, P.C.; Zheng, P.Y. Vitamin D Receptor Interacts with NLRP3 to Restrict the Allergic Response. Clin. Exp. Immunol. 2018,194,17-26. [CrossRef]
  62. Rao, Z.; Chen, X.; Wu, J.; Xiao, M.; Zhang, J.; Wang, B.; Fang, L.; Zhang, H.; Wang, X.; Yang, S.; et al. Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination. Front. Immunol. 2019,10, 2783. [CrossRef]
  63. Cui, C.; Wang, C.; Jin, F.; Yang, M.; Kong, L.; Han, W.; Jiang, P. Calcitriol Confers Neuroprotective Effects in Traumatic Brain Injury by Activating Nrf2 Signaling through an Autophagy-Mediated Mechanism. Mol. Med. 2021, 27,118. [CrossRef] [PubMed]
  64. Fao, L.; Mota, S.I.; Rego, A.C. Shaping the Nrf2-ARE-Related Pathways in Alzheimer's and Parkinson's Diseases. Ageing Res. Rev. 2019, 54,100942. [CrossRef] [PubMed]
  65. Ali, A.; Shah, S.A.; Zaman, N.; Uddin, M.N.; Khan, W.; Ali, A.; Riaz, M.; Kamil, A. Vitamin D Exerts Neuroprotection via SIRT1/Nrf-2/NF-KB Signaling Pathways against D-Galactose-Induced Memory Impairment in Adult Mice. Neurochem. Int. 2021, 142,104893. [CrossRef] [PubMed]
  66. Mehrabadi, S.; Sadr, S.S. Administration of Vitamin D3 and E Supplements Reduces Neuronal Loss and Oxidative Stress in a Model of Rats with Alzheimer's Disease. Neurol. Res. 2020, 42, 862-868. [CrossRef] [PubMed]
  67. Shinpo, K.; Kikuchi, S.; Sasaki, H.; Moriwaka, F.; Tashiro, K. Effect of 1,25-Dihydroxyvitamin D3 on Cultured Mesencephalic Dopaminergic Neurons to the Combined Toxicity Caused by L-Buthionine Sulfoximine and 1-Methyl-4-Phenylpyridine. J. Neurosci. Res. 2000, 62, 374-382. [CrossRef]
  68. Cui, X.; McGrath, J.J.; Burne, T.H.J.; Mackay-Sim, A.; Eyles, D.W. Maternal Vitamin D Depletion Alters Neurogenesis in the Developing Rat Brain. Int. J. Dev. Neurosci. 2007, 25, 227-232. [CrossRef]
  69. Zhu, Y.; Zhou, R.; Yang, R.; Zhang, Z.; Bai, Y.; Chang, F.; Li, L.; Sokabe, M.; Goltzman, D.; Miao, D.; et al. Abnormal Neurogenesis in the Dentate Gyrus of Adult Mice Lacking 1,25-Dihydroxy Vitamin D3 (1,25-(OH)2D3). Hippocampus 2012, 22, 421-433. [CrossRef]
  70. Eyles, D.; Almeras, L.; Benech, P.; Patatian, A.; Mackay-Sim, A.; McGrath, J.; Feron, F. Developmental Vitamin D Deficiency Alters the Expression of Genes Encoding Mitochondrial, Cytoskeletal and Synaptic Proteins in the Adult Rat Brain. J. Steroid Biochem. Mol. Biol. 2007,103, 538-545. [CrossRef]
  71. Almeras, L.; Eyles, D.; Benech, P.; Laffite, D.; Villard, C.; Patatian, A.; Boucraut, J.; Mackay-Sim, A.; McGrath, J.; Feron, F. Developmental Vitamin D Deficiency Alters Brain Protein Expression in the Adult Rat: Implications for Neuropsychiatric Disorders. PROTEOMICS 2007, 7, 769-780. [CrossRef] [PubMed]
  72. Eyles, D.; Brown, J.; Mackay-Sim, A.; McGrath, J.; Feron, F. Vitamin D3 and Brain Development. Neuroscience 2003,118, 641-653. [CrossRef]
  73. Feron, F.; Burne, T.H.J.; Brown, J.; Smith, E.; McGrath, J.J.; Mackay-Sim, A.; Eyles, D.W. Developmental Vitamin D3 Deficiency Alters the Adult Rat Brain. Brain Res. Bull. 2005, 65,141-148. [CrossRef] [PubMed]
  74. Naveilhan, P.; Neveu, I.; Wion, D.; Brachet, P. 1,25-Dihydroxyvitamin D3, an Inducer of Glial Cell Line-Derived Neurotrophic Factor. NeuroReport 1996, 7, 2171-2175. [CrossRef] [PubMed]
  75. Xu, Y.; Liang, L. Vitamin D3/Vitamin D Receptor Signaling Mitigates Symptoms of Post-Stroke Depression in Mice by Upregulat- ing Hippocampal BDNF Expression. Neurosci. Res. 2021,170, 306-313. [CrossRef]
  76. Koshkina, A.; Dudnichenko, T.; Baranenko, D.; Fedotova, J.; Drago, F. Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications. Nutrients 2019,11,1726. [CrossRef]
  77. Neveu, I.; Naveilhan, P.; Baudet, C.; Brachet, P.; Metsis, M. 1,25-Dihydroxyvitamin D3 Regulates NT-3, NT-4 but Not BDNF MRNA in Astrocytes. NeuroReport 1994, 6,124-126. [CrossRef]
  78. Scott-Solomon, E.; Kuruvilla, R. Mechanisms of Neurotrophin Trafficking via Trk Receptors. Mol. Cell. Neurosci. 2018, 91, 25-33. [CrossRef]
  79. Atif, F.; Yousuf, S.; Sayeed, I.; Ishrat, T.; Hua, F.; Stein, D.G. Combination Treatment with Progesterone and Vitamin D Hormone Is More Effective than Monotherapy in Ischemic Stroke: The Role of BDNF/TrkB/Erk1/2 Signaling in Neuroprotection. Neuropharmacology 2013, 67, 78-87. [CrossRef]
  80. Abdallah, C.G.; Sanacora, G.; Duman, R.S.; Krystal, J.H. Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annu. Rev. Med. 2015, 66, 509-523. [CrossRef]
  81. Li, N.; Lee, B.; Liu, R.J.; Banasr, M.; Dwyer, J.M.; Iwata, M.; Li, X.Y.; Aghajanian, G.; Duman, R.S. MTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. Science 2010, 329, 959-964. [CrossRef] [PubMed]
  82. Jovanovic, J.N.; Czernik, A.J.; Fienberg, A.A.; Greengard, P.; Sihra, T.S. Synapsins as Mediators of BDNF-Enhanced Neurotransmitter Release. Nat. Neurosci. 2000, 3, 323-329. [CrossRef] [PubMed]
  83. Alghamdi, S.; Alsulami, N.; Khoja, S.; Alsufiani, H.; Tayeb, H.O.; Tarazi, F.I. Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder. J. Mol. Neurosci. 2020, 70, 230-235. [CrossRef] [PubMed]
  84. Seyedi, M.; Gholami, F.; Samadi, M.; Djalali, M.; Effatpanah, M.; Yekaninejad, M.S.; Hashemi, R.; Abdolahi, M.; Chamari, M.; Honarvar, N.M. The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit/Hyperactivity Disorder. CNS Neurol. Disord.-Drug Targets 2019,18, 496-501. [CrossRef]
  85. Jiang, P.; Zhang, L.H.; Cai, H.L.; Li, H.D.; Liu, Y.P.; Tang, M.M.; Dang, R.L.; Zhu, W.Y.; Xue, Y.; He, X. Neurochemical Effects of Chronic Administration of Calcitriol in Rats. Nutrients 2014, 6, 6048-6059. [CrossRef] [PubMed]
  86. Pertile, R.A.N.; Cui, X.; Eyles, D.W. Vitamin D Signaling and the Differentiation of Developing Dopamine Systems. Neuroscience 2016, 333, 193-203. [CrossRef]
  87. Sabir, M.S.; Haussier, M.R.; Mallick, S.; Kaneko, I.; Lucas, D.A.; Haussier, C.A.; Whitfield, G.K.; Jurutka, P.W. Optimal Vitamin D Spurs Serotonin: 1,25-Dihydroxyvitamin D Represses Serotonin Reuptake Transport (SERT) and Degradation (MAO-A) Gene Expression in Cultured Rat Serotonergic Neuronal Cell Lines. Genes Nutr. 2018,13,19. [CrossRef]
  88. Luthold, R.V.; Fernandes, G.R.; Franco-de-Moraes, A.C.; Folchetti, L.G.D.; Ferreira, S.R.G. Gut Microbiota Interactions with the Immunomodulatory Role of Vitamin D in Normal Individuals. Metabolism 2017, 69, 76-86. [CrossRef]
  89. Assa, A.; Vong, L.; Pinnell, L.J.; Avitzur, N.; Johnson-Henry, K.C.; Sherman, P.M. Vitamin D Deficiency Promotes Epithelial Barrier Dysfunction and Intestinal Inflammation. J. Infect. Dis. 2014, 210,1296-1305. [CrossRef]
  90. Ooi, J.H.; Li, Y.; Rogers, C.J.; Cantorna, M.T. Vitamin D Regulates the Gut Microbiome and Protects Mice from Dextran Sodium Sulfate-Induced Colitis. J. Nutr. 2013,143,1679-1686. [CrossRef]
  91. Wu, S.; Liao, A.P.; Xia, Y.; Chun Li, Y.; Li, J.D.; Sartor, R.B.; Sun, J. Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-KB Activity in Intestine. Am. J. Pathol. 2010,177, 686-697. [CrossRef] [PubMed]
  92. Fedotova, J.; Dudnichenko, T.; Kruzliak, P.; Puchavskaya, Z. Different Effects of Vitamin D Hormone Treatment on Depression-like Behavior in the Adult Ovariectomized Female Rats. Biomed. Pharmacother. 2016, 84,1865-1872. [CrossRef] [PubMed]
  93. Fedotova, J.O. Vitamin D3 Treatment Differentially Affects Anxiety-like Behavior in the Old Ovariectomized Female Rats and Old Ovariectomized Female Rats Treated with Low Dose of 17ß-Estradiol. BMC Med. Genet. 2019, 20, 49. [CrossRef] [PubMed]
  94. Camargo, A.; Dalmagro, A.P.; Rikel, L.; da Silva, E.B.; Simäo da Silva, K.A.B.; Zeni, A.L.B. Cholecalciferol Counteracts Depressive- like Behavior and Oxidative Stress Induced by Repeated Corticosterone Treatment in Mice. Eur. J. Pharmacol. 2018, 833,451-461. [CrossRef]
  95. Da Silva Souza, S.V.; da Rosa, P.B.; Neis, V.B.; Moreira, J.D.; Rodrigues, A.L.S.; Moretti, M. Effects of Cholecalciferol on Behavior and Production of Reactive Oxygen Species in Female Mice Subjected to Corticosterone-Induced Model of Depression. Naunyn. Schmiedebergs Arch. Pharmacol. 2020, 393,111-120. [CrossRef]
  96. Neis, V.B.; Werle, I.; Moretti, M.; Rosa, P.B.; Camargo, A.; Dalsenter, Y.D.O.; Platt, N.; Rosado, A.F.; Engel, W.D.; de Almeida, GR.L.; et al. Involvement of Serotonergic Neurotransmission in the Antidepressant-like Effect Elicited by Cholecalciferol in the Chronic Unpredictable Stress Model in Mice. Metab. Brain Dis. 2022, 37,1597-1608. [CrossRef]
  97. Zhang, W.; Guo, Y.; Wang, K.; Chen, L.; Jiang, P. Neuroprotective Effects of Vitamin D and 17ß-Estradiol against Ovariectomy- Induced Neuroinflammation and Depressive-like State: Role of the AMPK/NF-KB Pathway. Int. Immunopharmacol. 2020, 86, 106734. [CrossRef]
  98. Bakhtiari-Dovvombaygi, H.; Izadi, S.; Zare Moghaddam, M.; Hashemzehi, M.; Hosseini, M.; Azhdari-Zarmehri, H.; Dinpanah, H; Beheshti, F. Beneficial Effects of Vitamin D on Anxiety and Depression-like Behaviors Induced by Unpredictable Chronic Mild Stress by Suppression of Brain Oxidative Stress and Neuroinflammation in Rats. Naunyn. Schmiedebergs Arch. Pharmacol. 2021, 394, 655-667. [CrossRef]
  99. Jiang, P.; Zhang, W.Y.; Li, H.D.; Cai, H.L.; Liu, Y.P.; Chen, L.Y. Stress and Vitamin D: Altered Vitamin D Metabolism in Both the Hippocampus and Myocardium of Chronic Unpredictable Mild Stress Exposed Rats. Psychoneuroendocrinology 2013, 38, 2091-2098. [CrossRef]
  100. Groves, N.J.; Bradford, D.; Sullivan, R.K.P.; Conn, K.A.; Aljelaify, R.F.; McGrath, J.J.; Burne, T.H.J. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are Not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus. PLoS ONE 2016,11, e0152328. [CrossRef]
  101. Jorde, R.; Sneve, M.; Figenschau, Y.; Svartberg, J.; Waterloo, K. Effects of Vitamin D Supplementation on Symptoms of Depression in Overweight and Obese Subjects: Randomized Double-Blind Trial. J. Intern. Med. 2008,264, 599-609. [CrossRef] [PubMed]
  102. Narula, N.; Cooray, M.; Anglin, R.; Muqtadir, Z.; Narula, A.; Marshall, J.K. Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study. Dig. Dis. Sci. 2017, 62, 448-455. [CrossRef] [PubMed]
  103. Penckofer, S.; Byrn, M.; Adams, W.; Emanuele, M.A.; Mumby, P.; Kouba, J.; Wallis, D.E. Vitamin D Supplementation Improves Mood in Women with Type 2 Diabetes. J. Diabetes Res. 2017,2017, 8232863. [CrossRef]
  104. Sharifi, A.; Vahedi, H.; Nedjat, S.; Mohamadkhani, A.; Hosseinzadeh Attar, M.J. Vitamin D Decreases Beck Depression Inventory Score in Patients with Mild to Moderate Ulcerative Colitis: A Double-Blind Randomized Placebo-Controlled Trial. J. Diet. Suppl. 2019,16, 541-549. [CrossRef] [PubMed]
  105. Yosaee, S.; Soltani, S.; Esteghamati, A.; Motevalian, S.A.; Tehrani-Doost, M.; Clark, C.C.T.; Jazayeri, S. Effects of Zinc, Vitamin D, and Their Co-Supplementation on Mood, Serum Cortisol, and Brain-Derived Neurotrophic Factor in Patients with Obesity and Mild to Moderate Depressive Symptoms: A Phase II, 12-Wk, 2 x 2 Factorial Design, Double-Blind, Randomized, PlaceboControlled Trial. Nutrition 2020, 71,110601. [CrossRef]
  106. Zhu, C.; Zhang, Y.; Wang, T.; Lin, Y.; Yu, J.; Xia, Q.; Zhu, P.; Zhu, D. Vitamin D Supplementation Improves Anxiety but Not Depression Symptoms in Patients with Vitamin D Deficiency. Brain Behav. 2020,10, e01760. [CrossRef] [PubMed]
  107. Hansen, J.P.; Pareek, M.; Hvolby, A.; Schmedes, A.; Toft, T.; Dahl, E.; Nielsen, C.T. Vitamin D3 Supplementation and Treatment Outcomes in Patients with Depression (D3-Vit-Dep). BMC Res. Notes 2019,12, 203. [CrossRef]
  108. Kaviani, M.; Nikooyeh, B.; Zand, H.; Yaghmaei, P.; Neyestani, T.R. Effects of Vitamin D Supplementation on Depression and Some Involved Neurotransmitters. J. Affect. Disord. 2020,269, 28-35. [CrossRef]
  109. Alavi, N.M.; Khademalhoseini, S.; Vakili, Z.; Assarian, F. Effect of Vitamin D Supplementation on Depression in Elderly Patients: A Randomized Clinical Trial. Clin. Nutr. 2019, 38, 2065-2070. [CrossRef]
  110. Bertone-Johnson, E.R.; Powers, S.I.; Spangler, L.; Larson, J.; Michael, Y.L.; Millen, A.E.; Bueche, M.N.; Salmoirago-Blotcher, E.; Wassertheil-Smoller, S.; Brunner, R.L.; et al. Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial. Am. J. Epidemiol. 2012,176,1-13. [CrossRef]
  111. Mozaffari-Khosravi, H.; Nabizade, L.; Yassini-Ardakani, S.M.; Hadinedoushan, H.; Barzegar, K. The Effect of 2 Different Single Injections of High Dose of Vitamin D on Improving the Depression in Depressed Patients With Vitamin D Deficiency: A Randomized Clinical Trial. J. Clin. Psychopharmacol. 2013, 33, 378-385. [CrossRef] [PubMed]
  112. Vellekkatt, F.; Menon, V.; Rajappa, M.; Sahoo, J. Effect of Adjunctive Single Dose Parenteral Vitamin D Supplementation in Major Depressive Disorder with Concurrent Vitamin D Deficiency: A Double-Blind Randomized Placebo-Controlled Trial. J. Psychiatr. Res. 2020,129, 250-256. [CrossRef] [PubMed]
  113. Khoraminya, N.; Tehrani-Doost, M.; Jazayeri, S.; Hosseini, A.; Djazayery, A. Therapeutic Effects of Vitamin D as Adjunctive Therapy to Fluoxetine in Patients with Major Depressive Disorder. Aust. N. Z. J. Psychiatry 2013,47, 271-275. [CrossRef] [PubMed]
  114. Eid, A.; Khoja, S.; AlGhamdi, S.; Alsufiani, H.; Alzeben, F.; Alhejaili, N.; Tayeb, H.O.; Tarazi, F.I. Vitamin D Supplementation Ameliorates Severity of Generalized Anxiety Disorder (GAD). Metab. Brain Dis. 2019, 34,1781-1786. [CrossRef] [PubMed]
  115. Valdivielso, J.M.; Fernandez, E. Vitamin D receptor polymorphisms and diseases. Clin. Chim. Acta 2006, 371,1-12. [CrossRef]
  116. Lye, M.S.; Tor, Y.S.; Tey, Y.Y.; Shahabudin, A.; Loh, S.P.; Ibrahim, N.; Stanslas, J.; Rosli, R.; Ling, K.H. BsmI-ApaI-TaqI TAC (BAt) Haplotype of Vitamin D Receptor Gene Is Associated with Increased Risk of Major Depressive Disorder. J. Mol. Neurosci. 2020, 71, 981-990. [CrossRef]
  117. Usategui-Martín, R.; De Luis-Román, D.A.; Fernández-Gómez, J.M.; Ruiz-Mambrilla, M.; Pérez-Castrillón, J.L. Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients 2022,14, 360. [CrossRef]

VitaminDWiki - Depression category contains

Some recent publications

14+ VitaminDWiki pages have ANXIETY in the title

This list is automatically updated

Items found: 15
Title Modified
International Adolescent Anxiety and suicide rates - GBD April 2024 07 Apr, 2024
Half as much anxiety and sleep problems if get lots of vitamin D from food (excluded getting D from supplements) – Feb 2024 23 Feb, 2024
Anxiety, Vitamin D, Omega-3 - many studies 23 Feb, 2024
Low Vitamin D is associated with risk of Depression 5X, Stress 4.8 X, and Anxiety 3.9 X (Saudi Arabia college students) – July 2023 29 Jul, 2023
Parkinson’s – Vitamin D, bone density, insomnia, falls, poor sleep, anxiety – March 2019 10 May, 2023
Anxiety and Depression decreased in senior prediabetics with weekly 25,000 IU of Vitamin D – RCT Sept 2022 22 Dec, 2022
Depression and Anxiety treatment with Vitamin D - probable molecular pathways - June 2022 21 Dec, 2022
Coronary Artery Disease Chest Pain, Anxiety, and Fatigue associated with low vitamin D – Oct 2022 07 Oct, 2022
Anxiety, depression, and suicide have recently surged (Note: Vitamin D, Omega-3, and Magnesium help) – May 2022 29 May, 2022
General Anxiety Disorder treated by weekly Vitamin D (50,000 IU -Omega-3, Mg also help) – Sept 2019 09 Dec, 2019
Omega-3 reduces Depression. Anxiety, Stress, PTSD, etc. – Aug 2018 02 Sep, 2019
Happy Nurses Project gave Omega-3 for 3 months – reduced depression, insomnia, anxiety, etc for a year – RCT July 2018 10 Nov, 2018
Anxiety severity reduced if more than 2 grams of Omega-3 – meta-analysis Sept 2018 19 Sep, 2018
Why is teen anxiety increasing so much (no mention of Magnesium, Vitamin D nor Omega-3) – Oct 2017 11 Oct, 2017
Salmon intervention (vitamin D and Omega-3) improved heart rate variability and reduced anxiety – Nov 2014 11 Feb, 2015

Attached files

ID Name Comment Uploaded Size Downloads
19008 Depression and A.jpg admin 21 Dec, 2022 106.30 Kb 662
19007 Molecular Basis U Vit D Depression and Anxiety.pdf admin 21 Dec, 2022 883.94 Kb 126