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Overview Schizophrenia and Vitamin D

Many reasons to think that schizophrenia is associated with low vitamin D
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
    Click here for some details
Omega-3 may treat schizophrenia wonder if Omega-3 and Vitamin D would be additive or even synergistic

Table of contents

See also Vitamin D Life

Omega-3 and Schizophrenia

B12 and Schizophrenia

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Types of evidence that Vitamin D helps brain problems - 2014
Pages in both of the categories of Intervention AND Cognitive

The Relationship between Symptom Severity and Low Vitamin D Levels in Patients with Schizophrenia.- Oct 2016

PLoS One. 2016 Oct 27;11(10):e0165284. doi: 10.1371/journal.pone.0165284. eCollection 2016.
Doğan Bulut S1, Bulut S2, Görkem Atalan D3, Berkol T4, Gürçay E5, Türker T6, Aydemir Ç7.

In recent years, the relationship between schizophrenia and environmental factors has come into prominence. This study investigated the relationship between vitamin D levels and the positive and negative symptoms of schizophrenia by comparing vitamin D levels between patients with schizophrenia and a healthy control group.
The study included 80 patients diagnosed with schizophrenia and 74 age- and sex-matched controls. The Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) were used to evaluate symptom severity. The 25-hydroxyvitamin D (25OHD) levels of all subjects both patients and healthy controls were analyzed in relation to measurements of symptom severity.
There were no significant differences between the groups in terms of age, sex, or physical activity. Their mean 25OHD levels were also similar (23.46±13.98ng/mL for the patient group and 23.69±9.61ng/mL for the control group). But when patients with schizophrenia were grouped based on their vitamin D levels, the results indicated a statistically significant differences between their vitamin D levels and their total SANS, affective flattening, and total SAPS, bizarre behavior and positive formal thought disorder scores (p = 0.019, p = 0.004, p = 0.015, p = 0.009 and p = 0.019, respectively). There is a negative correlation between 25OHD levels and SANS total points (r = -0.232, p = 0.038); a negative correlation for attention points (r = -0.227, p = 0.044) and negative correlation with positive formal thoughts (r = -0.257, p = 0.021).
The results of this study show a relationship between lower levels of vitamin D and the occurrence of positive and negative symptoms, along with increased severity of symptoms at lower levels of vitamin D, suggesting that treatment for schizophrenia should include assessment of patients' vitamin D levels. We recommend that patients with schizophrenia should be assessed with regard to their vitamin D levels.

PMID: 27788194 DOI: 10.1371/journal.pone.0165284  Download the PDF from Vitamin D Life

Vitamin D Council descripiton of this study

Clipped from Discussion
Of the schizophrenia patients who participated in our study,

  • 20% showed deficient levels of vitamin D;
  • 13.75% were found to have insufficient levels; and
  • 61.25% were found to have sufficient levels.

The healthy controls in our study showed 8.1% deficient, 28.4% insufficient and 63.5% sufficient levels of Vitamin D. Although the deficient percentage among the schizophrenia patients was higher, the levels found for vitamin D in our schizophrenia patients and healthy controls was not statistically significant.
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The differing results obtained in these studies could be the result of factors like darker complexions and geographic differences in where the studies were conducted.
Other factors may also make a difference for instance differences in phases of the disorder like acute or chronic stages. Also differences were observed between patients experiencing acute exacerbation and those in remission.
Greater levels of negative and positive symptoms may

  • increase nutritional problems,
  • reduce the amount of exposure to sunlight, and
  • encourage more sedentary lifestyle habits.

This may also account for lower levels of vitamin D in patients undergoing acute episodes of schizophrenia when compared with more similar levels in those in remission and in controls. It is also possible that the different scores could be a result of taking blood samples during different seasons of the year. Studies done by Graham et al. and Yuksel et al. [16,17] like ours, took care to gather blood samples during the same season. This could be a reason for the similar results obtained by our study and these others.
– – – – –
Associations between Vitamin D deficiency and obesity, smoking, and lack of physical activity have been shown in previous studies [40-43] and we analyzed those variables in the current study as well. Although there were significant differences between healthy controls and our patient group in terms of obesity and smoking, there was no statistically significant difference in their vitamin D values. Our study did not look carefully at nutrition and patients who took supplemental vitamin D. We know that, other than supplements, sunlight exposure is the primary source of vitamin D for the majority of people [44]. In our study, the similarity of vitamin D levels, despite large statistical differences between our schizophrenia patient group and controls in relation to smoking and obesity, supports the idea that sunlight is a very important factor. When patients with schizophrenia were grouped according to their levels of vitamin D deficiency, there were no statistically significant differences in terms of obesity and smoking between the groups. This finding strengthens the finding of a relationship between vitamin D deficiency and symptom severity.

Schizophreniform and Autism Spectrum Syndromes: both had very low levels of Vitamin D - Oct 2016

Vitamin D Deficiency in Adult Patients with Schizophreniform and Autism Spectrum Syndromes: A One-Year Cohort Study at a German Tertiary Care Hospital.
Front Psychiatry. 2016 Oct 6;7:168. eCollection 2016.
Endres D1, Dersch R2, Stich O2, Buchwald A3, Perlov E1, Feige B1, Maier S1, Riedel A1, van Elst LT1.

Vitamin D has many immunomodulatory, anti-inflammatory, and neuroprotective functions, and previous studies have demonstrated an association between vitamin D deficiency and neuropsychiatric disease. The aim of our study was to analyze the prevalence of vitamin D deficiency in a 1-year cohort of adult inpatients with schizophreniform and autism spectrum syndromes in a naturalistic inpatient setting in Germany.
Our study was comprised of 60 adult schizophreniform and 23 adult high-functioning autism spectrum patients who were hospitalized between January and December of 2015. We compared our findings with a historical German reference cohort of 3,917 adults using Pearson's two-sided chi-squared test. The laboratory measurements of 25-hydroxyvitamin D2/3 25(OH)vitamin D were obtained using a chemiluminescence immunoassay.
In the schizophreniform group, we found decreased (<20 ng/ml) 25(OH)vitamin D levels in 48/60 (80.0%) of the patients.
In the autism spectrum group, decreased levels were detected in 18/23 (78.3%) of the patients.
25(OH)vitamin D deficiencies were found in 57.3% of the historical control group.
Particularly, severe deficiencies (<10 ng/ml) occurred much more frequently in the schizophreniform (38.3%) and autism spectrum groups (52.2%),
when compared to the control group (16.3%).
The recommended 25(OH)vitamin D values of >30 ng/ml were observed in only 5% of the schizophreniform patients, 8.7% of the autism spectrum patients, and 21.9% of the healthy controls.
We found very high rates of 25(OH)vitamin D deficiencies in both patient groups and have discussed whether our findings might be related to alterations in the immunological mechanisms. Irrespective of the possible pathophysiological links between vitamin D deficiency and schizophrenia or autism spectrum disorders, a more frequent measurement of vitamin D levels seems to be justified in these patient groups. Further prospective, controlled, blinded, and randomized research should be conducted to analyze the effectiveness of vitamin D supplementation on the improvement of psychiatric symptoms.

PMID: 27766084 DOI: 10.3389/fpsyt.2016.00168 full free PDF online

Association between serum levels of bioavailable vitamin D and negative symptoms in first-episode psychosis - Sept 2016

Psychiatry Res. 2016 Sep 30;243:390-4. doi: 10.1016/j.psychres.2016.07.003. Epub 2016 Jul 5.
Yee JY1, See YM2, Abdul Rashid NA2, Neelamekam S2, Lee J3.
1Research Division, Institute of Mental Health, Singapore. jie_yin_yee at imh.com.sg.
2Research Division, Institute of Mental Health, Singapore.
3Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore; Department of General Psychiatry 1, Institute of Mental Health, Singapore.

Total vitamin D levels had been commonly reported to be lowered in patients with chronic psychotic illnesses in countries from the higher latitudes. However, studies on patients with first episode psychosis (FEP) are limited. In this study we investigated serum concentrations of total and bioavailable vitamin D levels in FEP patients compared to healthy controls and the association between symptom severity and vitamin D components. A total of 31 FEP patients and 31 healthy controls were recruited from Institute of Mental Health, Singapore. FEP patients were identified using Structured Clinical Interview for DSM-IV Axis I disorders (SCID-1) and severity symptoms were assessed using the positive and negative syndrome scale (PANSS). Sera from participants were analyzed for total vitamin D, vitamin D-binding protein (DBP) and bioavailable vitamin D. Linear regressions were performed to examine the associations between serum total and bioavailable vitamin D and the PANSS subscales. Current study noted a significantly lower bioavailable vitamin D was in the FEP group and an association between bioavailable vitamin D and negative symptoms in FEP patients in a population with a consistent supply of sun exposure throughout the year.

PMID: 27449008 DOI: 10.1016/j.psychres.2016.07.003 Free PDF online

Low Vitamin D might be an effect rather than a cause of schizophrenia - May 2016

Note: This study considerst vitamin D blood levels, not cell levels (3 genes can block cell levels and not be seen by blood tests)

Investigating causality in the association between 25(OH)D and schizophrenia
Sci Rep. 2016 May 24;6:26496. doi: 10.1038/srep26496.
Taylor AE1,2,3, Burgess S1,4, Ware JJ1,2,5, Gage SH1,2,3, Richards JB6,7,8, Davey Smith G1,5, Munafò MR1,2,3.

Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia.

PMID: 27215954 PMCID: PMC4877705 DOI: 10.1038/srep26496  Download the PDF from Vitamin D Life

97% of Schizophrenia patients were vitamin D deficient, and associated small brain volumes - June 2015

Psychiatry Res. 2015 Jun 24. pii: S0925-4927(15)30013-5. doi: 10.1016/j.pscychresns.2015.06.006. [Epub ahead of print]
Serum vitamin D and hippocampal gray matter volume in schizophrenia.
Shivakumar V1, Kalmady SV2, Amaresha AC2, Jose D2, Narayanaswamy JC2, Agarwal SM2, Joseph B2, Venkatasubramanian G3, Ravi V4, Keshavan MS5, Gangadhar BN6.

Disparate lines of evidence including epidemiological and case-control studies have increasingly implicated vitamin D in the pathogenesis of schizophrenia. Vitamin D deficiency can lead to dysfunction of the hippocampus - a brain region hypothesized to be critically involved in schizophrenia. In this study, we examined for potential association between serum vitamin D level and hippocampal gray matter volume in antipsychotic-naïve or antipsychotic-free schizophrenia patients (n=35). Serum vitamin D level was estimated using 25-OH vitamin D immunoassay. Optimized voxel-based morphometry was used to analyze 3-Tesla magnetic resonance imaging (MRI) (1-mm slice thickness). Ninety-seven percent of the schizophrenia patients (n=34) had sub-optimal levels of serum vitamin D (83%, deficiency; 14%, insufficiency).
A significant positive correlation was seen between vitamin D and regional gray matter volume in the right hippocampus after controlling for age, years of education and total intracranial volume (Montreal Neurological Institute (MNI) coordinates: x=35, y=-18, z=-8; t=4.34 pFWECorrected=0.018). These observations support a potential role of vitamin D deficiency in mediating hippocampal volume deficits, possibly through neurotrophic, neuroimmunomodulatory and glutamatergic effects.

PMID: 26163386

Schizophrenia 2X more likely if low vitamin D - meta-analysis July 2014

Serum Vitamin D Levels in Relation to Schizophrenia: A Systematic Review and Meta-Analysis of Observational Studies.
J Clin Endocrinol Metab. 2014 Jul 22:jc20141887. [Epub ahead of print]
Valipour G1, Saneei P, Esmaillzadeh A.

Introduction: Although several observational studies have investigated the association between vitamin D status and schizophrenia, we are aware of no comprehensive meta-analysis in this regard. Objective: We aimed to conduct a systematic review and a meta-analysis of observational studies to summarize the available data on the association between serum vitamin D levels and schizophrenia. Methods: A systematic research on all published articles until October 2013 was conducted in PubMed, ISI (Web of science), SCOPUS, and Google Scholar. All observational studies that had measured serum vitamin D levels in schizophrenic patients were included in the systematic review. After considering exclusion criteria, we had 19 studies for the systematic review that were included in three separate meta-analyses: 1) a meta-analysis on mean levels of 25-hydroxyvitamin D [25(OH)D] (n = 13); 2) a meta-analysis on the prevalence of vitamin D deficiency (n = 8); 3) a meta-analysis on odds ratios (n = 8). Results: Findings from a meta-analysis on means revealed that the overall mean difference in serum 25(OH)D levels between schizophrenic patients and control participants was -5.91 ng/mL [95% confidence interval (CI) -10.68, -1.14]. Subgroup analyses based on study design, the patient's hospitalization status, study quality, and study location did not explain between-study heterogeneity; however, type of biomarker assessed [25-dihydroxyvitamin D3 vs 25OH)D)] could account for some degree of heterogeneity. Results from the meta-analysis on the prevalence of vitamin D deficiency indicated that the overall prevalence of vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4%-84.2%).
Findings from the meta-analysis on odds ratios indicated that vitamin D-deficient persons were 2.16 times (95% CI 1.32, 3.56) more likely to have schizophrenia than those with vitamin D sufficiency. No evidence of heterogeneity was detected. Conclusion: We found a strong association between vitamin D deficiency and schizophrenia. However, randomized clinical trials are required to confirm our findings.
PMID: 25050991
PDF is attached at the bottom of this page

Vitamin D Deficiency Doubles Risk of Developing Schizophrenia Vitamin D3 Blog Aug 2014
Review of the study, along with 2 short videos.

  • Study of Vitamin D in the Severely Mentally Ill Clinical trial underway using 50,000 IU of vitamin D weekly for 3 months
    Comment on trial results expected in 2013 by Vitamin D Life
    Would have greatly increased their chance of success if they had doubled both the dose and the time period, or had used a loading dose.
    50,000 IU weekly, without a loading dose, will get some of the participants up to 40 nanograms of vitamin D by 3 months.
    Trial success would have been greater if they had a quick goal of >50 nanograms.
  • Searched US clinical trials: (depressed OR depression OR schizophrenia OR psychotic OR psychosis OR autistic OR autism) "vitamin D" 47 interventions with vitamin D as of May 2014
    Vitamin D for Improving Metabolic Control and Depressive Symptoms (50,000 IU weekly)
    The Role of Vitamin D Supplementation on Well Being and Symptoms of Depression During the Winter Season in Health Service Staff (2800 IU)
    Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression (2800 IU)

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Low serum vitamin D concentrations in patients with schizophrenia. - 2012

Itzhaky D, Amital D, Gorden K, Bogomolni A, Arnson Y, Amital H.
Isr Med Assoc J. 2012 Feb;14(2):88-92.
50 schizophrenic patients: average of 15 nanograms of vitamin D
PDF is attached at the bottom of this page
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New Zealand study shows that vitamin D deficiency is common in psychiatric inpatients, - 2012%%%particularly among patients with schizophrenia and those of Maori descent.

BMC Psychiatry 2012; 12: 68 Provisional PDF attached at the bottom of this page

  • schizophrenia patients had lowest mean level = 14 nanograms
  • 34% of schizophrenia-spectrum disorder patients were severely vitamin D deficient, vs 9% of other patients
  • Maori (dark skin) descent 14 severely deficient, vs 5 non-Maori

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Psychotic are 3.5X more likely to be vitamin D deficient or have dark skin - 2012

Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study.
BMC Psychiatry. 2012 May 9;12(1):38.
Gracious BL, Finucane TL, Freidman-Campbell M, Messing S, Parkhurst MM.

BACKGROUND: Vitamin D deficiency is a re-emerging epidemic, especially in minority populations. Vitamin D is crucial not only for bone health but for proper brain development and functioning. Low levels of vitamin D are associated with depression, seasonal affective disorder, and schizophrenia in adults but little is known about vitamin D and mental health in the pediatric population.

METHODS: One hundred four adolescents presenting for acute mental health treatment over a 16-month period were assessed for vitamin D status and the relationship of 25-OH vitamin D levels to severity of illness, defined by presence of psychotic features.

RESULTS: Vitamin D deficiency (25-OH D levels <20 ng/ml) was present in 34%; vitamin D insufficiency (25-OH D levels 20-30 ng/ml) was present in 38%, with a remaining 28% in the normal range.
Adolescents with psychotic features had lower vitamin D levels (20.4 ng/ml vs. 24.7 ng/ml; p=0.04, 1 df).
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 1.113.4; p<0.04). Race was no longer associated with psychosis when the results were adjusted for vitamin D level.

CONCLUSIONS: Vitamin D deficiency and insufficiency are both highly prevalent in adolescents with severe mental illness. The preliminary associations between vitamin D deficiency and presence of psychotic features warrant further investigation as to whether vitamin D deficiency is a mediator of illness severity, result of illness severity, or both. Higher prevalence of vitamin D deficiency but no greater risk of psychosis in African Americans, if confirmed, may have special implications for health disparity and treatment outcome research.

PMID: 22571731
CLICK HERE for PDF online
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Comment on previous study by Vitamin D Council

Study: Low vitamin D linked to psychosis in teens May 2012

Posted on May 24, 2012 by John Cannell, MD
Psychosis, or loss of touch with reality, is difficult to see in any loved one but is particularly difficult to deal with if it’s your teenager.
Dr. Barbara Gracious and colleagues recently discovered that of 104 teenagers assessed at an acute mental health clinic, the teenagers with the lowest vitamin D levels were more likely to be psychotic.
In what must be a tribute to video games and the like, 72% of the teenagers had vitamin D levels lower than 30 ng/ml and 34% had levels lower than 20 ng/ml.

The magnitude of the vitamin D effect was not minor; if the teenager had low vitamin D levels, he or she was almost four times (OR=3.5) as likely to be psychotic.

Gracious BL, Finucane TL, Freidman-Campbell M, Messing S, Parkhurst MM.
Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study.
BMC Psychiatry. 2012 May 9;12(1):38.

I was disappointed with their usual call for more studies instead of the needed call to treat vitamin D deficiency now. Compare Dr. Gracious’s approach to that of Dr. Mats Humble’s approach at Sweden’s Karolinska Institute. Dr. Humble and colleagues assessed 117 mental health outpatients of all ages and found that teenagers had the lowest levels. Teenage females had vitamin D levels of around 20 ng/ml and, in another nod to video games, teenage Swedish males attending a mental health clinic had average vitamin D level of around 10 ng/ml.

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 Jul;121(1-2):467-70. Epub 2010 Mar 7.

Dr. Humble also found that depressed, psychotic and autistic patients had the lowest vitamin D levels and anxiety patients had the highest levels.
Instead of just calling for more trials, he treated the deficient patients with up to 4,000 IU/day of cholecalciferol or, in other cases, up to 70,000 IU weekly of ergocalciferol, which resulted in “considerable improvement” in psychosis and depression.

No doubt, Dr. Humble is busy conducting a randomized controlled trial. At least I hope so. Moreover, I hope he is using pharmacological doses of vitamin D, not physiological doses. That is, I hope he is using 10,000 IU/day and not 5,000 IU/day, although some may claim 10,000 IU/day is physiological.

I predict the day will come when using 50,000 IU/day for ten days in very ill people with a vitamin D responsive disease, such as sepsis, congestive heart failure, and perhaps psychosis, to name but a few, will be commonplace.
Now, 50,000/day is a pharmacological dose, which simply means the vitamin D is being used as a drug and not as a supplement for good health.
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Incidence of Schizophrenia and Other Psychoses in England, 1950–2009: A Systematic Review and Meta-Analyses (dark skin)

  • Study in Britain
    Did not notice increasing incidence over time
    5.6 X more likely if black Caribbean
    4.7 X more likely if black African
    2.4 X more likely if South Asian

CLICK HERE for full text on-line
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Vitamin D, Birth Weight, and Schizophrenia Risk Psychology Today Sept 2011

Discusses two studies, one of which concluded with:
We found an association between being small for gestational age (defined as birth weights in the population >2 SDs less than the normal birth weight for a particular gestational age) and

  • any psychiatric diagnosis (OR, 1.35; 95% confidence interval CI, 1.29-1.42),
  • schizophrenia (OR, 1.34; 95% CI, 1.14-1.58),
  • affective disorders (OR 1.16; 95% CI, 1.02-1.31),
  • alcohol and drug disorders (OR, 1.36; 95% CI, 1.27-1.46), and
  • neurotic, stress-related, and somatoform disorders (OR, 1.32; 95% CI, 1.20-1.46) as well as an
  • association between low gestational age (<37 weeks) and any
  • psychiatric diagnosis (OR, 1.25; 95% CI, 1.19-1.32),

CLICK HERE for full PDF online
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Simple Eye Tests Accurately Identify Schizophrenia Medcape Nov 2012

Nothing about vitamin D, but interesting anyway
monitoring eye movement correctly discriminated between those with and without Schizophrenia with 98.3% accuracy
Note: voice analysis (132 characteristics) appears able to predict Parkinson's Overview Parkinsons and Vitamin D
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Hyperprolinemia 3X more frequent in schizophrenics with low vitamin D - 2014

Vitamin D insufficiency and schizophrenia risk: Evaluation of hyperprolinemia as a mediator of association
James D. Clelland, Laura L. Read, Valérie Drouet, Angela Kaon, Alexandra Kelly, Karen E. Duff, Robert H. Nadrich, Amit Rajparia, Catherine L. Clellandemail address
Received 23 July 2013; received in revised form 13 March 2014; accepted 19 March 2014. published online 01 May 2014.

25-Hydroxyvitamin D (25(OH)D) deficits have been associated with schizophrenia susceptibility and supplementation has been recommended for those at-risk. Although the mechanism by which a deficit confers risk is unknown, vitamin D is a potent transcriptional modulator and can regulate proline dehydrogenase (PRODH) expression. PRODH maps to chromosome 22q11, a region conferring the highest known genetic risk of schizophrenia, and encodes proline oxidase, which catalyzes proline catabolism. l-Proline is a neuromodulator at glutamatergic synapses, and peripheral hyperprolinemia has been associated with decreased IQ, cognitive impairment, schizoaffective disorder, and schizophrenia.

We investigated the relationship between 25(OH)D and schizophrenia, comparing fasting plasma 25(OH)D in 64 patients and 90 matched controls. We then tested for a mediating effect of hyperprolinemia on the association between 25(OH)D and schizophrenia.

25(OH)D levels were significantly lower in patients, and 25(OH)D insufficiency associated with schizophrenia (OR 2.1, adjusted p=0.044, 95% CI: 1.02–4.46). Moreover, 25(OH)D insufficient subjects had three times greater odds of hyperprolinemia than those with optimal levels (p=0.035, 95% CI: 1.08–8.91), and formal testing established that hyperprolinemia is a significantly mediating phenotype that may explain over a third of the effect of 25(OH)D insufficiency on schizophrenia risk.

This study presents a mechanism by which 25(OH)D insufficiency confers risk of schizophrenia; via proline elevation due to reduced PRODH expression, and a concomitant dysregulation of neurotransmission. Although definitive causality cannot be confirmed, these findings strongly support vitamin D supplementation in patients, particularly for those with elevated proline, who may represent a large subgroup of the schizophrenia population.

References are on-line

Vitamin D Council Blog on this article behind a $5/month firewall

  • It is known that the highest genetic risk for developing schizophrenia occurs in people that have a mutation in a gene that affects their ability to break down proline, an amino acid that acts like an excitatory neurotransmitter in the brain.
  • more than one quarter of schizophrenic patients have elevated proline levels

Association between first-episode schizophrenia and low vitamin D - Feb 2014, includes PDF

Relationship of low vitamin D status with positive, negative and cognitive symptom domains in people with first-episode schizophrenia.
Early Interv Psychiatry. 2014 Feb 24. doi: 10.1111/eip.12122. [Epub ahead of print]
Graham KA1, Keefe RS, Lieberman JA, Calikoglu AS, Lansing KM, Perkins DO.

AIM: Deficient vitamin D levels are very common among Americans of all ages and ethnicities, but little is known about its prevalence or associated problems among those with schizophrenia.

METHODS: Stored plasma from 20 recent onset schizophrenia subjects and 20 matched healthy comparison subjects were analysed for 25 OH vitamin D, and related to measures of symptom severity and neurocognition.

RESULTS: There was no significant difference in mean 25 OH vitamin D between the schizophrenia and the healthy comparison subjects (28.2 standard deviation (SD) 12.6 ng mL-1 vs. 29.9 SD 14.3 ng mL-1 ), and about half the subjects in each group had insufficient levels (<30 ng mL-1 ). Among psychosis subjects, greater severity of negative symptoms was correlated with lower vitamin D status (r = -0.55, P = 0.012); the correlations of overall symptom severity and positive symptom severity with 25 OH vitamin D levels approached significance (r = -0.42, P = 0.07 and r = -0.36, P = 0.12, respectively). There was no relationship of vitamin D with depressive symptoms. Among the schizophrenia subjects, lower 25 OH vitamin D levels were associated with more severe overall cognitive deficits (r = 0.56, P = 0.019).

CONCLUSION: This study found that lower vitamin D levels in schizophrenia subjects were associated with more severe negative symptoms and overall cognitive deficits. However, the cross-sectional design precludes any conclusions about whether low vitamin D status in fact causes more severe negative symptoms and cognitive impairments. No relationship was found between lower vitamin D levels and depressive symptoms.

Graph from attached PDF: 40 ng line added by Vitamin D Life
PMID: 24612563 PDF is attached at the bottom of this page


Schizophrenics 6X more likely to be anxious if <10 ng of Vitamin D - Sept 2018

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.
Psychiatry Res. 2018 Sep 13;270:104-110. doi: 10.1016/j.psychres.2018.09.024.

RESULTS: Hypovitaminosis D has been found in 21.4% of the subjects and none of them had received vitamin D supplementation in the previous 12 months. In multivariate analysis, hypovitaminosis D has been significantly associated with respectively higher depressive symptoms (aOR = 1.18 [1.03-1.35], p = 0.02) and current anxiety disorder (aOR = 6.18 [2.15-17.75], p = 0.001), independently of age and gender. No association of hypovitaminosis D with respectively positive and negative symptoms, cognitive scores or other biological variables has been found (all p > 0.05), however, a trend toward significance has been found for metabolic syndrome (p = 0.06).

Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms (aOR = 0.67 [0.46-0.98], p = 0.04) and lower rate of current anxiety disorder (aOR = 0.06 [0.01-0.66], p = 0.02) compared to patients with hypovitaminosis D.

See also web

  • Do schizophrenia patients age early? August 2014
    We also propose a role of vitamin D, neuroimmunological changes and elevated oxidative stress as well as mitochondrial dysfunction in addition to the above factors with 'vitamin-D deficiency' as the central paradox
  • More than 100 genes linked to schizophrenia identified CBS News July 2014
    Looked at 150,000 people; of which 37,000 had been diagnosed with schizophrenia. (no mention of vitamin D)
    Found 108 genetic markers, 83 of them not previously reported.
    people with the most genetic markers were 15 X more likely to have schizophrenia than those with the fewest markers.
     Download the PDF from Nature.
  • Schizophrenia is 'Orchestra' of Eight Genetically Distinct Disorders with Own Symptoms IBT Sept 2014
    In some patients with hallucinations or delusions, for example, the researchers matched distinct genetic features to patients' symptoms.
    In another group, they found that disorganised speech and behaviour were specifically associated with a set of DNA variations that carried a 100% risk of the illness.
    "When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don't act independently. They work in concert to disrupt the brain's structure and function, and that results in the illness,"
  • Vitamin D deficiency and schizophrenia 7 minute video, Dec 2015
  • schizophrenia Mercola Nov 2016? has the following sections
    Learn More About Schizophrenia; Schizophrenia: Misconception, Facts and Information; What Is Schizophrenia
    Types of Schizophrenia; Schizophrenia in Children; What Causes Schizophrenia?; Is Schizophrenia Hereditary?
    Signs and Symptoms of Schizophrenia; Schizophrenia Diagnosis and Test; Treatment for Schizophrenia
    Famous People with Schizophrenia; Schizophrenia Prevention; Living With Schizophrenia

Single dose of CBD (600 mg) reset Schizophrenic brains (for a while) - Oct 2018

Single Dose of CBD Resets Schizophrenic Brains GreenMedInfo

Reporting on: Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis A Randomized Clinical Trial
 Download the PDF from Sci-Hub via Vitamin D Life
fMRI brain scans 4 hours after ingesting 600 mg of CBD
No indication of long-term benefit (only a single fMRI was taken)

Overview Schizophrenia and Vitamin D        
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11012 CBD brain activation.jpg admin 08 Dec, 2018 18:42 17.76 Kb 1865
11011 CBD Schiz Sci-Hub.pdf PDF 2018 admin 08 Dec, 2018 18:27 2.16 Mb 631
7663 Investigating causality in the association between 25(OH)D and schizophrenia.pdf PDF admin 14 Jan, 2017 18:20 1.03 Mb 1384
7662 PLOS T4.jpg admin 14 Jan, 2017 18:00 99.20 Kb 4731
7661 PLOS Schiz.jpg admin 14 Jan, 2017 17:59 27.16 Kb 5732
7660 Schizophrenia PLOS.PDF PDF admin 14 Jan, 2017 17:59 1.04 Mb 1348
6825 Malacards schiz.jpg admin 23 Jun, 2016 16:51 63.14 Kb 6196
4175 Schizophrenia F3.jpg admin 23 Jul, 2014 12:35 38.46 Kb 11563
4174 schizophrenia July 2014.pdf PDF 2014 admin 23 Jul, 2014 12:34 225.43 Kb 1949
4172 schizophrenia Genes Nature July 2014.pdf PDF 2014 admin 23 Jul, 2014 11:53 5.43 Mb 2231
3979 Schiz.jpg admin 29 May, 2014 13:04 30.74 Kb 10745
3978 first-episode schizophrenia.pdf PDF 2014 admin 29 May, 2014 12:59 411.40 Kb 1956
1445 psychiatric inpatients - June 2012.pdf admin 09 Jul, 2012 12:42 248.44 Kb 2663
1438 Schizophrenia- Feb 2012.pdf admin 05 Jul, 2012 21:08 92.98 Kb 2334
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