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Vitamin D deficiency, behavioral atypicality, anxiety and depression in children with chromosome 22q11.2 deletion syndrome

Published online by Cambridge University Press:  28 July 2016

L. Kelley
Affiliation:
Department of Psychology, University of New Orleans, New Orleans, LA, USA
A. F. P. Sanders
Affiliation:
Department of Psychology, University of New Orleans, New Orleans, LA, USA
E. A. Beaton*
Affiliation:
Department of Psychology, University of New Orleans, New Orleans, LA, USA
*
*Address for correspondence: E. A. Beaton, Department of Psychology, University of New Orleans, 2000 Lakeshore Drive, New Orleans, LA 70148, USA. (Email ebeaton@uno.edu)

Abstract

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex developmental disorder with serious medical, cognitive and emotional symptoms across the lifespan. This genetic deletion also imparts a lifetime risk for developing schizophrenia that is 25–30 times that of the general population. The origin of this risk is multifactorial and may include dysregulation of the stress response and immunological systems in relation to brain development. Vitamin D is involved in brain development and neuroprotection, gene transcription, immunological regulation and influences neuronal signal transduction. Low levels of vitamin D are associated with schizophrenia, depression and anxiety in the general population. Yet, little is known about how vitamin D levels in children with 22q11.2DS could mediate risk of psychosis in adulthood. Blood plasma levels of vitamin D were measured in children aged 7–16 years with (n=11) and without (n=16) 22q11.2DS in relation to parent reports of children’s anxiety and atypicality. Anxiety and atypicality in childhood are risk indicators for the development of schizophrenia in those with 22q11.2DS and the general population. Children with 22q11.2DS had lower vitamin D levels, as well as elevated anxiety and atypicality compared with typical peers. Higher levels of anxiety, depression and internalizing problems but not atypicality were associated with lower levels of vitamin D. Vitamin D insufficiency may relate to higher levels of anxiety and depression, in turn contributing to the elevated risk of psychosis in this population. Further study is required to determine casual linkages between anxiety, stress, mood and vitamin D in children with 22q11.2DS.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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References

1. Karayiorgou, M, Simon, TJ, Gogos, JA. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat Rev Neurosci. 2010; 11, 402416.Google Scholar
2. Shprintzen, RJ, Higgins, AM, Antshel, K, et al. Velo-cardio-facial syndrome. Curr Opin Pediatr. 2005; 17, 725730.Google Scholar
3. Tang, SX, Yi, JJ, Calkins, ME, et al. Psychiatric disorders in 22q11.2 deletion syndrome are prevalent but undertreated. Psychol Med. 2014; 44, 12671277.CrossRefGoogle ScholarPubMed
4. Beaton, EA, Simon, TJ.. How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome? J Neurodev Disord. 2011; 3, 6875.Google Scholar
5. Gothelf, D, Gruber, R, Presburger, G, et al. Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study. J Clin Psychiatry. 2003; 64, 11631169.CrossRefGoogle ScholarPubMed
6. Sobin, C, Kiley-Brabeck, K, Karayiorgou, M. Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome. Mol Psychiatry. 2005; 10, 553562.Google Scholar
7. Antshel, KM, Shprintzen, R, Fremont, W, et al. Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry. 2010; 49, 333344.Google ScholarPubMed
8. Swillen, A, Vandeputte, L, Cracco, J, et al. Neuropsychological, learning and psychosocial profile of primary school aged children with the velo-cardio-facial syndrome (22q11 deletion): evidence for a nonverbal learning disability? Child Neuropsychol. 1999; 5, 230241.Google Scholar
9. Angkustsiri, K, Leckliter, I, Tartaglia, N, et al. An examination of the relationship of anxiety and intelligence to adaptive functioning in children with chromosome 22q11. 2 deletion syndrome. J Dev Behav Pediatr. 2012; 33, 713720.Google Scholar
10. Fung, WLA, McEvilly, R, Fong, J, et al. Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome. Am J Psychiatry. 2010; 167, 998.Google Scholar
11. Niarchou, M, Zammit, S, van Goozen, SH, et al. Psychopathology and cognition in children with 22q11. 2 deletion syndrome. Br J Psychiatry. 2014; 204, 4654.Google Scholar
12. Stephenson, DD, Beaton, EA, Weems, CF, Angkustsiri, K, Simon, TJ. Identifying patterns of anxiety and depression in children with chromosome 22q11. 2 deletion syndrome: comorbidity predicts behavioural difficulties and impaired functional communications. Behav Brain Res. 2014; 276, 190198.CrossRefGoogle ScholarPubMed
13. Schneider, M, Van der Linden, M, Menghetti, S, et al. Predominant negative symptoms in 22q11.2 deletion syndrome and their associations with cognitive functioning and functional outcome. J Psychiatr Res. 2014; 48, 8693.CrossRefGoogle ScholarPubMed
14. Gothelf, D, Feinstein, C, Thompson, T, et al. Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. Am J Psychiatry. 2007; 164, 663669.CrossRefGoogle ScholarPubMed
15. Gothelf, D, Schneider, M, Green, T, et al. Risk factors and the evolution of psychosis in 22q11. 2 deletion syndrome: a longitudinal 2-site study. J Am Acad Child Adolesc Psychiatry. 2013; 52, 11921203, e1193.CrossRefGoogle ScholarPubMed
16. Grober, U, Spitz, J, Reichrath, J, Kisters, K, Holick, M. Vitamin D: update 2013: from rickets prophylaxis to general preventive healthcare. Dermatoendocrinol. 2013; 5, 331347.Google Scholar
17. Willis, KS, Smith, DT, Broughton, KS, Larson-Meyer, DE. Vitamin D status and biomarkers of inflammation in runners. Open Access J Sports Med. 2012; 3, 3542.Google Scholar
18. Pojednic, RM, Ceglia, L, Lichtenstein, AH, Dawson-Hughes, B, Fielding, RA. Vitamin D receptor protein is associated with interleukin-6 in human skeletal muscle. Endocrine. 2014; 49, 512520.Google Scholar
19. Pojednic, RM, Ceglia, L, Olsson, K, et al. Effects of 1, 25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells. Calcif Tissue Int. 2015; 96, 256263.Google Scholar
20. Muscogiuri, G, Palomba, S, Caggiano, M, et al. Low 25 (OH) vitamin D levels are associated with autoimmune thyroid disease in polycystic ovary syndrome. Endocrine. 2015; 53, 538542.CrossRefGoogle ScholarPubMed
21. Adorini, L, Penna, G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008; 4, 404412.CrossRefGoogle ScholarPubMed
22. Holick, MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004; 80, 1678S1688S.Google Scholar
23. Cieslak, K, Feingold, J, Antonius, D, et al. Low vitamin D levels predict clinical features of schizophrenia. Schizophr Res. 2014; 159, 543545.CrossRefGoogle ScholarPubMed
24. Graham, KA, Keefe, RS, Lieberman, JA, et al. Relationship of low vitamin D status with positive, negative and cognitive symptom domains in people with first-episode schizophrenia. Early Interv Psychiatry. 2014; 9, 397405.Google Scholar
25. Itzhaky, D, Amital, D, Gorden, K, et al. Low serum vitamin D concentrations in patients with schizophrenia. Isr Med Assoc J. 2012; 14, 8892.Google Scholar
26. Kjaergaard, M, Waterloo, K, Wang, CEA, et al. Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry. 2012; 201, 360368.Google Scholar
27. Maddock, J, Berry, DJ, Geoffroy, M-C, Power, C, Hyppönen, E. Vitamin D and common mental disorders in mid-life: cross-sectional and prospective findings. Clin Nutr. 2013; 32, 758764.CrossRefGoogle ScholarPubMed
28. McGrath, JJ, Burne, TH, Féron, F, Mackay-Sim, A, Eyles, DW. Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull. 2010; 36, 10731078.Google Scholar
29. Jones, G, Prosser, DE, Kaufmann, M. Cytochrome P450-mediated metabolism of vitamin D. J Lipid Res. 2013; 55, 1331.Google Scholar
30. Jones, G, Prosser, DE, Kaufmann, M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012; 523, 918.Google Scholar
31. Eyles, DW, Smith, S, Kinobe, R, Hewison, M, McGrath, JJ. Distribution of the vitamin D receptor and 1α-hydroxylase in human brain. J Chem Neuroanat. 2005; 29, 2130.CrossRefGoogle ScholarPubMed
32. Jiang, P, Zhang, W-Y, Li, H-D, et al. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats. Psychoneuroendocrinology. 2013; 38, 20912098.CrossRefGoogle ScholarPubMed
33. Schuster, I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011; 1814, 186199.CrossRefGoogle ScholarPubMed
34. Haussler, MR, Mangelsdorf, DJ, Komm, BS, et al. Molecular biology of the vitamin D hormone. Proceedings of the 1987 Laurentian Hormone Conference, Elsevier BV, pp. 263–305, 1988.CrossRefGoogle Scholar
35. Mangelsdorf, DJ, Thummel, C, Beato, M, et al. The nuclear receptor superfamily: the second decade. Cell. 1995; 83, 835839.CrossRefGoogle ScholarPubMed
36. Prüfer, K, Veenstra, TD, Jirikowski, GF, Kumar, R. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord. J Chem Neuroanat. 1999; 16, 135145.Google Scholar
37. Christakos, S, Dhawan, P, Liu, Y, Peng, X, Porta, A. New insights into the mechanisms of vitamin D action. J Cell Biochem. 2003; 88, 695705.CrossRefGoogle ScholarPubMed
38. Sequeira, VB, Rybchyn, MS, Tongkao-on, W, et al. The role of the vitamin D receptor and ERp57 in photoprotection by 1α,25-dihydroxyvitamin D3 . Mol Endocrinol. 2012; 26, 574582.CrossRefGoogle Scholar
39. Bernd, P. The role of neurotrophins during early development. Gene Expr. 2008; 14, 241250.Google Scholar
40. Barker, T, Martins, TB, Hill, HR, et al. Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. Eur J Appl Physiol. 2013; 113, 15231534.CrossRefGoogle ScholarPubMed
41. Ibi, M, Sawada, H, Nakanishi, M, et al. Protective effects of 1α,25-(OH)2D3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology. 2001; 40, 761771.Google Scholar
42. Favalli, G, Li, J, Belmonte-de-Abreu, P, Wong, AHC, Daskalakis, ZJ. The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res. 2012; 46, 111.CrossRefGoogle ScholarPubMed
43. Wang, Y, Chiang, YH, Su, TP, et al. Vitamin D3 attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology. 2000; 39, 873880.Google Scholar
44. Zhang, Y, Leung, DYM, Richers, BN, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012; 188, 21272135.Google Scholar
45. Miller, GE, Chen, E, Parker, KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011; 137, 959997.Google Scholar
46. Schwieler, L, Larsson, MK, Skogh, E, et al. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia – significance for activation of the kynurenine pathway. J Psychiatry Neurosci. 2015; 40, 126133.Google Scholar
47. Kalmady, SV, Venkatasubramanian, G, Shivakumar, V, et al. Relationship between interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naïve schizophrenia: evidence for differential susceptibility? PLoS ONE. 2014; 9, e96021.Google Scholar
48. Yong, DEJ, Booth, P, Baruni, J, et al. Chromosome 22q11 microdeletion and congenital heart disease – a survey in a paediatric population. Eur J Pediatr. 1999; 158, 566570.CrossRefGoogle Scholar
49. Sieberer, M, Haltenhof, H, Haubitz, B, et al. Basal ganglia calcification and psychosis in 22q11.2 deletion syndrome. Eur Psychiatry. 2005; 20, 567569.Google Scholar
50. Jyonouchi, S, McDonald-McGinn, DM, Bale, S, Zackai, EH, Sullivan, KE. CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009; 123, e871e877.Google Scholar
51. Kar, P, Ogoe, B, Poole, R, Meeking, D. Di-George syndrome presenting with hypocalcaemia in adulthood: two case reports and a review. J Clin Pathol. 2005; 58, 655657.CrossRefGoogle ScholarPubMed
52. Kapadia, CR, Kim, YE, McDonald-McGinn, DM, Zackai, EH, Katz, LEL. Parathyroid hormone reserve in 22q11.2 deletion syndrome. Genet Med. 2008; 10, 224228.CrossRefGoogle ScholarPubMed
53. Kinney, DK, Hintz, K, Shearer, EM, et al. A unifying hypothesis of schizophrenia: abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction. Med Hypotheses. 2010; 74, 555563.Google Scholar
54. McLean-Tooke, A, Spickett, GP, Gennery, AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol. 2007; 66, 17.CrossRefGoogle ScholarPubMed
55. Taylor, S, Morris, G, Wilson, D, Davies, S, Gregory, J. Hypoparathyroidism and 22q11 deletion syndrome. Arch Dis Child. 2003; 88, 520522.Google Scholar
56. Cheung, ENM, George, SR, Costain, GA, et al. Prevalence of hypocalcaemia and its associated features in 22q11.2 deletion syndrome. Clin Endocrinol. 2014; 81, 190196.Google Scholar
57. Wheeler, AL, Shoback, DM. Clinical presentation of hypoparathyroidism. In Hypoparathyroidism (eds. Brandi LM, Brown ME), 2015; pp. 155–165. Springer, Milan.Google Scholar
58. Brauner, R, de Gonneville, ALH, Kindermans, C, et al. Parathyroid function and growth in 22q11.2 deletion syndrome. J Pediatr. 2003; 142, 504508.Google Scholar
59. Bassett, AS, McDonald-McGinn, DM, Devriendt, K, et al. Practical guidelines for managing patients with 22q11. 2 deletion syndrome. J Pediatr. 2011; 159, 332339, e331.Google Scholar
60. Cui, X, Gooch, H, Groves, NJ, et al. Vitamin D and the brain: key questions for future research. J Steroid Biochem Mol Biol. 2015; 148, 305309.Google Scholar
61. Kalueff, AV, Lou, Y-R, Laaksi, I, Tuohimaa, P. Impaired motor performance in mice lacking neurosteroid vitamin D receptors. Brain Res Bull. 2004; 64, 2529.Google Scholar
62. Zou, J, Minasyan, A, Keisala, T, et al. Progressive hearing loss in mice with a mutated vitamin D receptor gene. Audiol Neurootol. 2008; 13, 219230.Google Scholar
63. Burne, T, McGrath, J, Eyles, D, Mackaysim, A. Behavioural characterization of vitamin D receptor knockout mice. Behav Brain Res. 2005; 157, 299308.Google Scholar
64. Kalueff, A, Loseva, E, Haapasalo, H, et al. Thalamic calcification in vitamin D receptor knockout mice. Neuroreport. 2006; 17, 717721.Google Scholar
65. Thompson, E, Kline, E, Reeves, G, Pitts, SC, Schiffman, J. Identifying youth at risk for psychosis using the behavior assessment system for children. Schizophr Res. 2013; 151, 238244.Google Scholar
66. Reynolds, CR, Kamphaus, RW. Manual for Behavior Assessment System for Children. 1992. AGS Publishing: Circle Pine, MN.Google Scholar
67. Wechsler, D. WISC-IV Technical and Interpretive Manual. 2003. The Psychological Corporation: San Antonio, TX.Google Scholar
68. Mowry, B, Holmans, P, Pulver, A, et al. Multicenter linkage study of schizophrenia loci on chromosome 22q. Mol Psychiatry. 2004; 9, 784795.CrossRefGoogle ScholarPubMed
69. Goodman, B, Rutberg, J, Lin, W, Pulver, A, Thomas, G, Geraghty, M. Hyperprolinaemia in patients with deletion (22)(q11. 2) syndrome. J Inherit Metab Dis. 2000; 23, 847848.Google Scholar
70. Clelland, CL, Read, LL, Baraldi, AN, et al. Evidence for association of hyperprolinemia with schizophrenia and a measure of clinical outcome. Schizophr Res. 2011; 131, 139145.Google Scholar
71. Clelland, JD, Read, LL, Drouet, V, et al. Vitamin D insufficiency and schizophrenia risk: evaluation of hyperprolinemia as a mediator of association. Schizophr Res. 2014; 156, 1522.Google Scholar
72. Roussos, P, Giakoumaki, SG, Bitsios, P. A risk PRODH haplotype affects sensorimotor gating, memory, schizotypy, and anxiety in healthy male subjects. Biol Psychiatry. 2009; 65, 10631070.CrossRefGoogle ScholarPubMed
73. Schneider, M, Debbané, M, Bassett, AS, et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the international consortium on brain and behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014; 171, 627639.Google Scholar
74. Shivakumar, V, Kalmady, SV, Amaresha, AC, et al. Serum vitamin D and hippocampal gray matter volume in schizophrenia. Psychiatry Res. 2015; 233, 175179.CrossRefGoogle ScholarPubMed
75. Debbané, M, Schaer, M, Farhoumand, R, Glaser, B, Eliez, S. Hippocampal volume reduction in 22q11.2 deletion syndrome. Neuropsychologia. 2006; 44, 23602365.Google Scholar
76. DeBoer, T, Wu, Z, Lee, A, Simon, TJ. Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment. Behav Brain Funct. 2007; 3, 54.Google Scholar
77. Jiang, P, Xue, Y, Li, H-D, et al. Dysregulation of vitamin D metabolism in the brain and myocardium of rats following prolonged exposure to dexamethasone. Psychopharmacology. 2014; 231, 34453451.Google Scholar
78. Jiang, P, Zhang, L, Zhu, W, et al. Chronic stress causes neuroendocrine-immune disturbances without affecting renal vitamin D metabolism in rats. J Endocrinol Invest. 2014; 37, 11091116. : 10.1007/s40618-014-0191-5.Google Scholar
79. Jorde, R, Mathiesen, EB, Rogne, S, et al. Vitamin D and cognitive function: the Tromsø Study. J Neurol Sci. 2015; 355, 155161.Google Scholar
80. Van der Schaft, J, Koek, H, Dijkstra, E, Verhaar, H, van der Schouw, Y, Emmelot-Vonk, M. The association between vitamin D and cognition: a systematic review. Ageing Res Rev. 2013; 12, 10131023.Google Scholar
81. Wehr, H, Bednarska-Makaruk, M. Vitamin D and cognition. Adv Psychiatry Neurol. 2016; 25, 4953.Google Scholar
82. Sigwalt, AR, Budde, H, Helmich, I, et al. Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression. Neuroscience. 2011; 192, 661674.Google Scholar
83. Obradovic, D, Gronemeyer, H, Lutz, B, Rein, T. Cross-talk of vitamin D and glucocorticoids in hippocampal cells. J Neurochem. 2006; 96, 500509.Google Scholar
84. Ansari, NN, Spilioti, E, Kalotychou, V, et al. Vitamin D decreases in vitro glucocorticoid sensitivity via down regulation of glucocorticoid receptor expression. Endocr Abstr. 2015; 37 OC5.2. Google Scholar
85. Diamond, DM, Bennett, MC, Fleshner, M, Rose, GM. Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus. 1992; 2, 421430.Google Scholar
86. Joëls, M. Corticosteroid effects in the brain: U-shape it. Trends Pharmacol Sci. 2006; 27, 244250.Google Scholar
87. Walker, E, Mittal, V, Tessner, K. Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia. Annu Rev Clin Psychol. 2008; 4, 189216.Google Scholar
88. Corcoran, CM, Smith, C, McLaughlin, D, et al. HPA axis function and symptoms in adolescents at clinical high risk for schizophrenia. Schizophr Res. 2012; 135, 170174.Google Scholar
89. Karanikas, E, Antoniadis, D, Garyfallos, GD. The role of cortisol in first episode of psychosis: a systematic review. Curr Psychiatry Rep. 2014; 16, 503.Google Scholar
90. Labad, J, Stojanovic-Pérez, A, Montalvo, I, et al. Stress biomarkers as predictors of transition to psychosis in at-risk mental states: roles for cortisol, prolactin and albumin. J Psychiatr Res. 2015; 60, 163169.Google Scholar
91. Karanikas, E, Garyfallos, G. Role of cortisol in patients at risk for psychosis mental state and psychopathological correlates: a systematic review. Psychiatry Clin Neurosci. 2015; 69, 268282.Google Scholar
92. Pruessner, M, Béchard-Evans, L, Boekestyn, L, et al. Attenuated cortisol response to acute psychosocial stress in individuals at ultra-high risk for psychosis. Schizophr Res. 2013; 146, 7986.CrossRefGoogle ScholarPubMed
93. Frighi, V, Morovat, A, Stephenson, MT, et al. Vitamin D deficiency in patients with intellectual disabilities: prevalence, risk factors and management strategies. Br J Psychiatry. 2014; 205, 458464.Google Scholar
94. Grant, WB, Wimalawansa, SJ, Holick, MF, et al. Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities. Nutrients. 2015; 7, 15381564.Google Scholar
95. Bicíková, M, Dusková, M, Vítku, J, et al. Vitamin D in anxiety and affective disorders. Physiol Res. 2015; 64, S101S103.Google Scholar
96. Black, LJ, Jacoby, P, Allen, KL, et al. Low vitamin D levels are associated with symptoms of depression in young adult males. Aust N Z J Psychiatry. 2014; 48, 464471.Google Scholar
97. Wu, C, Ren, W, Cheng, J, et al. Association between serum levels of vitamin D and the risk of post-stroke anxiety. Medicine. 2016; 95, e3566.Google Scholar
98. Bertone-Johnson, ER. Vitamin D and the occurrence of depression: causal association or circumstantial evidence? Nutr Rev. 2009; 67, 481492.Google Scholar
99. Holick, MF, Binkley, NC, Bischoff-Ferrari, HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96, 19111930.Google Scholar
100. Moyad, MA. Heart Health = Urologic Health and Heart Unhealthy = Urologic Unhealthy: rapid review of lifestyle changes and dietary supplements. Urol Clin North Am. 2011; 38, 359367.Google Scholar