Toggle Health Problems and D

First episode psychosis associated with a 33 percent lower vitamin D in 3 races – Sept 2013


Vitamin D deficiency in first episode psychosis: A case-control study.

Schizophr Res. 2013 Sep 20. pii: S0920-9964(13)00472-6. doi: 10.1016/j.schres.2013.08.036.
Crews M, Lally J, Gardner-Sood P, Howes O, Bonaccorso S, Smith S, Murray RM, Di Forti M, Gaughran F.
Bromley Assertive Outreach and Rehabilitation Team, Oxleas NHS Foundation Trust, London, United Kingdom; Institute of Psychiatry, King's College London, London, United Kingdom.

BACKGROUND: Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP).

METHOD: We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis.

RESULTS: Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827).

CONCLUSIONS: We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.

© 2013 Elsevier B.V. All rights reserved.
PMID: 24060571


  • Almeras L, Eyles D, Benech P, Laffite D, Villard C, Patatian A, et al. Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics. 2007;7(5):769–780
  • Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, et al. Long-chain omega−3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch. Gen. Psychiatry. 2010;67(2):146–154
  • Bebbington PE, Nayani T. The Psychosis Screening Questionnaire. Int. J. Methods Psychiatr. Res. 1995;5:11–19
  • Berg AO, Melle I, Torjesen PA, Lien L, Hauff E, Andreassen OA. A cross-sectional study of vitamin D deficiency among immigrants and Norwegians with psychosis compared to the general population. J. Clin. Psychiatry. 2010;71(12):1598–1604
  • Berk M, Jacka FN, Williams LJ, Ng F, Dodd S, Pasco JA. Is this D vitamin to worry about? Vitamin D insufficiency in an inpatient sample. Aust. N. Z. J. Psychiatry. 2008;42(10):874–878
  • Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv. Exp. Med. Biol. 2008;624:55–71
  • Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am. J. Clin. Nutr. 2006;84(1):18–28
  • Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, et al. Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif. Tissue Int. 2006;78(5):257–270
  • Brot C, Jorgensen NR, Sorensen OH. The influence of smoking on vitamin D status and calcium metabolism. Eur. J. Clin. Nutr. 1999;53(12):920–926
  • Chang C-K, Hayes RD, Perera G, Broadbent MTM, Fernandes AC, Lee WE, et al. Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London. PLoS One. 2011;6(5):1–6
  • Cutillas-Marco E, Fuertes-Prosper A, Grant WB, Morales-Suarez-Varela M. Vitamin D deficiency in South Europe: effect of smoking and aging. Photodermatol. Photoimmunol. Photomed. 2012;28(3):159–161
  • Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front. Neuroendocrinol. 2013;34(1):47–64
  • Ford L, Graham V, Wall A, Berg J. Vitamin D concentrations in an UK inner-city multicultural outpatient population. Ann. Clin. Biochem. 2006;43(Pt 6):468–473
  • Fuller KE, Casparian JM. Vitamin D: balancing cutaneous and systemic considerations. South. Med. J. 2001;94(1):58–64
  • Gama R, Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, et al. Hypovitaminosis D and disease: consequence rather than cause?. BMJ. 2012;345:(e5706-e5706)
  • Grandi NC, Breitling LP, Brenner H. Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Prev. Med. 2010;51(3–4):228–233
  • Groves NJ, Kesby JP, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH. Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice. Behav. Brain Res. 2013;241:120–131
  • Harvey NC, Cooper C. Vitamin D: some perspective please. BMJ. 2012;345:e4695;(Jul 19)
  • Hermann AP, Brot C, Gram J, Kolthoff N, Mosekilde L. Premenopausal smoking and bone density in 2015 perimenopausal women. J. Bone Miner. Res. 2000;15(4):780–787
  • Hewison M. Vitamin D and innate and adaptive immunity. Vitam. Horm. 2011;86:23–62
  • Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am. J. Clin. Nutr. 2004;80(6 Suppl.):1678S–1688S
  • Holick MF. Diabetes and the vitamin D connection. Curr. Diab. Rep. 2008;8(5):393–398
  • Honasoge M, Rao DS. Metabolic bone disease in gastrointestinal, hepatobiliary, and pancreatic disorders and total parenteral nutrition. Curr. Opin. Rheumatol. 1995;7(3):249–254
  • Humble MB, Gustafsson S, Bejerot S. Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. J. Steroid Biochem. Mol. Biol. 2010;121(1–2):467–470
  • Hypponen E, Power C. Hypovitaminosis D in British adults at age 45y: nationwide cohort study of dietary and lifestyle predictors. Am. J. Clin. Nutr. 2007;85(3):860–868
  • Iuliano-Burns S, Wang XF, Ayton J, Jones G, Seeman E. Skeletal and hormonal responses to sunlight deprivation in Antarctic expeditioners. Osteoporos. Int. 2009;20(9):1523–1528
  • Klontz KC, Acheson DW. Dietary supplement-induced vitamin D intoxication. N. Engl. J. Med. 2007;357(3):308–309
  • Lally J, Gardner-Sood P, Howes O, Smith S, Atakan Z, Greenwood K, et al. Vitamin D Deficiency in Schizophrenia—A Need for Increased Vigilance?. In: International Congress on Schizophrenia Research (ICOS-R), Orlando, Florida. 2013;
  • Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone. 2002;30(5):771–777; Full-Text PDF (116 KB)
  • Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am. J. Clin. Nutr. 2008;88(6):1519–1527
  • McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?. FASEB J. 2008;22(4):982–1001
  • McGrath J. Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?. Schizophr. Res. 1999;40(3):173–177; Full-Text PDF (74 KB)
  • McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Jarvelin MR, et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr. Res. 2004;67(2–3):237–245; Full-Text PDF (124 KB)
  • 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(6):1073–1078
  • McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, Burne TH, et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case–control study. Arch. Gen. Psychiatry. 2010;67(9):889–894
  • McGrath J, Brown A, St Clair D. Prevention and schizophrenia—the role of dietary factors. Schizophr. Bull. 2011;37(2):272–283
  • Meaney AM, Smith S, Howes OD, O'brien M, Murray RM, O'keane V. Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br. J. Psychiatry. 2004;184(6):503–508
  • Menkes DB, Lancaster K, Grant M, Marsh RW, Dean P, du Toit SA. Vitamin D status of psychiatric inpatients in New Zealand's Waikato region. BMC Psychiatry. 2012;12:68
  • Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol. Psychiatry. 2011;70(7):663–671; Full-Text PDF (326 KB)
  • Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos. Int. 2009;20(11):1807–1820
  • Orton SM, Ramagopalan SV, Para AE, Lincoln MR, Handunnetthi L, Chao MJ, et al. Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. J. Neurol. Sci. 2011;305(1–2):116–120
  • Pack AM, Gidal B, Vazquez B. Bone disease associated with antiepileptic drugs. Cleve. Clin. J. Med. 2004;71(2):S42–S48
  • Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ. 2010;11(340):142–147
  • Rosen CJ. Clinical practice. Vitamin D insufficiency. N. Engl. J. Med. 2011;364(3):248–254
  • Skversky AL, Kumar J, Abramowitz MK, Kaskel FJ, Melamed ML. Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001–2006. J. Clin. Endocrinol. Metab. 2011;96(12):3838–3845
  • Tiangga E, Gowda A, Dent JA. Vitamin D deficiency in psychiatric in-patients and treatment with daily supplements of calcium and ergocalciferol. Psychiatr. Bull. 2008;32(10):390–393
  • Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clin. Neurol. Neurosurg. 2010;112(1):1–10; Full-Text PDF (217 KB)
  • Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10(2):1–13
  • Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–511
  • Wang L, Song Y, Manson JE, Pilz S, Marz W, Michaelsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ. Cardiovasc. Qual. Outcomes. 2012;5(6):819–829
  • Wharton B, Bishop N. Rickets. Lancet. 2003;362(9393):1389–1400; Full-Text PDF (311 KB)
  • White T, Anjum A, Schulz C. The schizophrenia prodrome. Am. J. Psychiatry. 2006;163:376–380
  • Wood H. Multiple sclerosis: sunlight and vitamin D influence multiple sclerosis risk independently of HLA-DRB1ast15 status. Nat. Rev. Neurol. 2012;8(3):122-122
  • World Health Organisation . WHO Scientific Group on the Prevention and Management of Osteoporosis: Report of a WHO Scientific Group. Geneva: World Health Organisation; 2003;
  • Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 2000;72(3):690–693
  • Zadshir A, Tareen N, Pan D, Norris K, Martins D. The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Ethn. Dis. 2005;15(Suppl. 4-5):97–101

See also VitaminDWiki

ADHD, Autism, Early Psychosis and Omega-3 – review Dec 2017

1) 97% of patients with schizophrenia are vitamin D deficient
2) Schizophrenia varies with latitude (UVB) by 10X (controversy)
3) Schizophrenia is more common in those with dark skin (when away from the equator)
4) Schizophrenia is associated with low natal vitamin D
5) Schizophrenia has been increasing around the world when vitamin D has been decreasing (controversy)
6) Schizophrenia is associated with low birth rate, which is associated with low vitamin D
7) Schizophrenia is associated with Autism which is associated with low vitamin D
8) Schizophrenia Bulletin Editorial (Jan 2014) speculated that Vitamin D could be a major player
9) Schizophrenia 2X more likely if low vitamin D - meta-analysis
10) Schizophrenia increased 40 % for Spring births after Danes stopped vitamin D fortification
11) Schizophrenia is associated with season of birth
12) Schizophrenia is associated with poor Vitamin D Receptor genes
13) Schizophrenia risk is decreased if give Vitamin D after birth
14) Schizophrenia symptoms reduced when Vitamin D levels are restored

See also web

Vitamin D status: Connection to first episode of psychosis?
Vitamin D Council review of this study, Oct 2013, Behind a $5 a month paywall
Nanogram/ml levels

Whites Blacks Asians
Cases: 18 9.6 10
Controls: 27 14 16
  • Vitamin D insufficiency in psychiatric inpatients.
    J Psychiatr Pract. 2013 Jul;19(4):296-300. doi: 10.1097/01.pra.0000432599.24761.c1.
    The mean vitamin D level on admission was 22.3 ng/mL, with a range of 4-79.2 ng/mL. The incidence of vitamin D insufficiency (defined as levels < 30 ng/mL) was 75%.
  • Ethnic minority position and risk for psychotic disorders (in Netherlands)
    Curr Opin Psychiatry. 2013 Mar;26(2):166-71. doi: 10.1097/YCO.0b013e32835d9e43.
    A meta-analysis found that both first and second-generation migrants have on average a two-fold increase in risk for psychotic disorders.
    (That is, dark skinned people, which typically have lower vitamin D, were 2X more likely to have psychotic disorders)
  • Vitamin D deficiency and psychotic features in mentally ill adolescents: a cross-sectional study.
    BMC Psychiatry. 2012 May 9;12:38. doi: 10.1186/1471-244X-12-38.
    The association for vitamin D deficiency and psychotic features was substantial (OR 3.5; 95% CI 1.4-8.9; p <0.009).
    Race was independently associated with vitamin D deficiency and independently associated with psychosis for those who were Asian or biracial vs. white (OR=3.8; 95% CI 1.1‒13.4; p<0.04).
  • Review of the study in MedScape
    Previous research has shown that individuals with psychotic disorders often have vitamin D deficiency. However, this could be caused by long periods of hospitalization, use of anticonvulsant medications, or poor diet, note the investigators.
    69 adult inpatients (39% men; 56% white, 29% black, 14% Asian; mean age, 31 years
    14.6 ng vs 21.5 ng, Deficiency 36.2% vs 15.9%

They note 3 possible causes for the association:

  1. During the often long prodromal phase, many patients with schizophrenia withdraw from normal activities, and this might result in a reduction in sunlight exposure.
  2. Having low levels of vitamin D over a long period may be a risk factor for developing psychosis.
  3. Because vitamin D is a negative acute-phase reactant, levels can decrease during an inflammatory response.
    Comment on MedScape: My clinical experience shows that "sick" patients require a lot more vit D3 supplements than usual and than healthier patients to maintain the same blood levels . It seems that the active phases of illness consume this vitamin in a fashion similar to how patients with colds can tolerate higher levels of vitamin C supplementation before they get loose stools when compared to their tolerated level when healthy.

Attached files

ID Name Comment Uploaded Size Downloads
5027 phychosis.jpg admin 04 Feb, 2015 63.67 Kb 2665