Hindawi

Psychiatry Journal
Volume 2019, Article ID 7839287, 7 pages
https://doi.org/10.1155/2019/7839287

Research Article
Symptomatic Correlates of Vitamin D Deficiency
in First-Episode Psychosis

1 2
Ricardo Coentre and Inês Canelas da Silva
1
Department of Psychiatry, Hospital de Santa Maria, Centro Hospitalar Universitario´ Lisboa Norte EPE/Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal

2
Department of Psychiatry, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal
Correspondence should be addressed to Ricardo Coentre; [email protected]

Received 21 November 2018; Revised 14 March 2019; Accepted 7 April 2019; Published 2 May 2019

Academic Editor: Luca Ferraro

Copyright © 2019 Ricardo Coentre and Inesˆ Canelas da Silva. Tis is an open access article distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.

Previous studies indicate that low levels of vitamin D are associated with increased severity of psychiatric symptoms in chronic
multiepisode psychosis (MEP). We aimed to compare vitamin D levels between rst-episode psychosis (FEP) and MEP and to
investigate the correlations between vitamin D levels and symptoms in FEP patients. Te participants were adults aged 18-4
years who presented with a ective and non-a ective FEP to an early intervention team in Portugal. Depression was assessed
using the Beck Depression Inventory, and positive and negative symptoms and general psychopathology were measured with
the Positive and Negative Syndrome Scale. Blood samples were analyzed for 2 -hydroxyvitamin D (2 OHD). Tirty-three
patients completed the study in the FEP group and in the MEP group. FEP patients had low levels of 2 OHD (18.1 ±7.48
ng/mL), with no signi cant di erences from MEP patients. Low 2 OHD was signi cantly correlated with high severities of
depressive (r=-0.484, p=0.004) and negative (r=-0.480, p=0.00 ) symptoms as well as general psychopathology (r=-0. 9,
p=0.001) in FEP patients. Multiple regression revealed an inverse association between general psychopathology and vitamin D
level (p=0.027). More investigation of the association of vitamin D and schizophrenia is needed, namely, using a nonpatient
control group and trying to clarify possible causality between vitamin D and psychiatric symptoms.

1. Introduction 1,2 (OH)2D are transported in the circulation by vitamin D-

binding protein, which is a water-soluble carrier protein. Only
Vitamin D de ciency is traditionally associated with mus- 1% of the metabolites bind weakly to albumin to freely
culoskeletal consequences [1]. In recent years vitamin D circulate in the bloodstream, and it is the free fraction of the
has been associated with psychiatric disorders [2]. hormone that is the biologically active component [7].
Vitamin D is primarily produced by skin exposure to Vitamin D levels in the general population are higher in
ultraviolet B sunlight with diet contributing with a small men than in women, they decrease with increasing age [8],
percentage (a maximum of 20%) [ ]. Vitamin D levels vary and because vitamin D is fat soluble and stored in adipose
seasonally with lower levels occurring during the late winter tissue, those with obesity have lower circulating levels [9].
and early spring that re ect the levels of ambient sunlight [4]. Tere is also a relationship between low levels of vitamin D
People with pigmented skin need more sunlight to produce and tobacco [10], because tobacco increases hepatic
vitamin D, and lower levels of vitamin D are observed in cytochrome enzyme activity and consequently alters
Black and Asian populations [ ]. Serum 2 -hydroxyvitamin vitamin D metabolism [11].
D (2 OHD) is considered the optimal vitamin D status Vitamin D is involved in several brain processes, includ-
indicator [ ], and its hydroxylation in the kidneys pro-duces ing neurodevelopment, neurotrophic activities, and growth
1,2 -dihydroxyvitamin D (1,2 (OH)2D), which is the active factor regulation, and vitamin D also has a neuroprotective
metabolite. Approximately 8 -90% of 2 OHD and role [12]. Several studies have suggested that vitamin D levels
2 Psychiatry Journal

are related to the development of psychosis [2]; namely, a substance abuse or dependence, organic psychosis,
correlation between low early life vitamin D levels and presence of major medical/neurological disease, and an
schizophrenia has been suggested [1 , 14]. Tere is also inability to understand and complete the assessments.
evidence of increased prevalence of schizophrenia in urban Te subjects were provided full information about the
environments, among dark-skinned migrants, among those nature and purpose of the study and were informed of the
with winter births and those at higher latitudes [1 , 1 ]. It has possibility of terminating their participation at any time. Tis
been hypothesized that vitamin D could be responsible for study was conducted in accordance with the ethical
these results [1 ]. Vitamin D de ciency could be a modi able principles contained in the Declaration of Helsinki. Te
risk factor for psychotic disorders. Published studies have research protocol was approved by Hospital Vila Franca de
mainly included patients with established and chronic psy- Xira Ethics Committee, and written informed consent was
chotic disorders and populations living at high latitudes with obtained from all participants.
signi cant seasonal periods [2]. Few studies exist regarding the
early phases of psychosis and involving those living in 2.2. Methods. At program entry, a trained consultant psy-
low/medium latitude countries. Indeed, the published research chiatrist collected detailed sociodemographic and clinical
does not clarify the main question: is vitamin D de ciency the data as part of the initial routine clinical care of FEP
cause and/or consequence of psychosis [17]? patients. Te clinical data included the duration of untreated
Several studies have demonstrated an inverse correla-tion psychosis (DUP), depressive symptoms, positive
between vitamin D levels and positive, negative and symptoms, negative symptoms, general psychopathology,
depressive symptoms in chronic psychosis [17, 18]. Few and adherence to medication.
studies have researched vitamin D in rst-episode psychosis Te duration of untreated psychosis was determined
(FEP) patients [19–2 ]. Only two studies have evaluated the using the Nottingham Onset Schedule (NOS) [2 ] and was
association between vitamin D and symptoms in FEP. In de ned as the period of time from the onset of psychotic
Singapore, Yee et al. (201 ) found an association between low symptoms to treatment with antipsychotic med-ication. Te
levels of bioavailable vitamin D and negative symptoms in diagnoses were established using the Opera-tional Criteria
FEP patients [2 ]. Additionally, in North Carolina, USA, Checklist for Psychotic Illness and A ective Illness
Graham et al. (201 ) found that a greater severity of negative (OPCRIT+) [2 , 2 ]. Te OPCRIT+ is a checklist that
symptoms was correlated with lower vitamin D status in rst- includes items related to psychiatric history and psy-
episode schizophrenia patients [20]. Also, some published chopathology. Te checklist ratings are entered into the
studies indicate that anticonvulsant medication could have a OPCRIT+ so ware, which generates a diagnosis for the
negative e ect on vitamin D levels [24]. main categories of a ective and psychotic disorders as de
Te aims of the present study were as follows: (1) to ned according to major classi cation systems including the
investigate vitamin D levels in a ective and non-a ective FEP DSM-IV. Te OPCRIT+ has been demonstrated to have
in a medium latitude country (40∘ N) that provides signi cant good reliability when used by di erent raters. Te rater was
sunlight exposure during the entire year, (2) to compare an experienced consultant psychiatrist who was trained in
vitamin D levels in FEP subjects with those in chronic the use of the OPCRIT+.
multiepisode psychosis (MEP) subjects, and ( ) to examine the Positive and negative symptoms and general
relationship between vitamin D levels and symptom severity psychopathology were assessed with the Positive and Negative
(positive, negative, and depressive symptoms and general Syndrome Scale (PANSS) [27]. Tis scale is composed of three
psychopathology) in FEP. We hypothesized that FEP patients subscales that evaluate positive symptoms, negative
would have low levels of vitamin D that do not di er from symptoms, and general psychopathology in schizophrenia.
those in MEP patients, which would re ect the early presence Each item is scored from 1 (absent) to 7 (extreme). Te positive
of vitamin D de ciency in psychotic disorders. We also subscale includes 7 items about positive symptoms (e.g.,
hypothesized that FEP patients would exhibit negative delusions, hallucinatory behavior, and hostility), and the total
correlations of vitamin D with general, negative, and depres- score varies between 7 and 49. Te negative subscale includes
sive symptoms similar to the results that have been found in items related to negative symptoms (e.g., blunted a ect, poor
previous studies of MEP. rapport, or di culty in abstract thinking), and the total score
varies between 7 and
2. Material and Methods 49. Te general psychopathology subscale includes a variety
of items related to psychopathology other than positive and
2.1. Subjects. All participants were part of a larger prospective negative symptoms, including anxiety, depression, somatic
study of FEP at the First-Episode Psychosis Program (PPEP) concern, lack of judgment and insight, and poor impulse
in Vila Franca de Xira, Portugal. Te PPEP is a special-ized control. Te total score for the general psychopathology
early intervention program that provides medical and subscale varies between 1 and 112.
psychosocial treatment and follow-up for a ective and non-a Depressive symptoms were evaluated with the Beck
ective FEP patients to a catchment area with a population of Depression Inventory (BDI) [28]. Tis instrument is a 21-
24 ,000. Patients aged 18 to 4 from the local catchment area question, multiple-choice, and self-report inventory that is
who were consecutively admitted between January 201 and used to evaluate the incidence and severity of depression
March 2017 were eligible for participation in the study. Te symptoms with a total score between 0 and . Te version of
exclusion criteria were the following: a primary diagnosis of the BDI scale that had been translated into the Portuguese
Psychiatry Journal

language and validated for the Portuguese population was with antipsychotic alone, (18.18%) with antipsychotic plus
used [28, 29]. To examine attitude and adherence behavior antidepressant, and 2 ( .0 %) with mood stabi-
towards antipsychotic treatment, the Medication Adherence lizer/anticonvulsivant plus antipsychotic. Tere was no evi-
Rating Scale (MARS) was applied [ 0]. Tis scale has 10 yes dence of the e ect of medication on vitamin D levels,
or no questions about medication and behavior toward including anticonvulsivant medication. Only two patients
medication and results in a total score that ranges from 0 to on FEP group (mean vitamin D level 14.4 ng/mL) and four
10; higher scores indicate better adherence. Te Global on MEP group (mean vitamin D level: 20.9 ng/mL) were
Assessment of Functioning Scale (GAF) was used to prescribed anticonvulsants, all with valproic acid.
evaluate general functioning [ 1]. Te GAF subjectively
evaluates social, occupational, and psychological 3.2. Correlation Analysis. Te 2 OHD level was inversely
functioning, and the nal score ranges from 1 (severely correlated with negative symptom (r=-0.480, p=0.00 ) and
impaired) to 100 (extremely high functioning). general psychopathology (r=-0. 9, p=0.001) scores on the
Blood collection was performed between 8.00 and 9.00 PANSS and with the depressive symptom (r=-0.484,
am upon entry to the study. Blood was withdrawn by p=0.004) scores as evaluated with the BDI in the FEP
venipuncture into tubes containing SST for the collection of group. No correlation was found between 2 OHD level and
the serum. Te optimal vitamin D status indicator, i.e., 2 - positive symptoms (Table 2) in the FEP sample. Also, no
hydroxyvitamin D (2 OHD), was obtained by chemilumi- signi cant correlations were found between vitamin D
nescent immunoassay. Te 2 OHD levels were classi ed as levels and DUP, MARS, and GAF scores. Multiple linear
su cient if the value was ≥ 0 ng/mL and insu cient if the regression analysis examining the associations of positive,
value was < 0 ng/mL. negative, general psychopathology, and depressive
symptoms (independent variables) with 2 -hydroxyvitamin
2.3. Statistical Analysis. Te data were analyzed using IBM D (dependent variable) revealed an inverse correlation with
SPSS Statistics version 24. Te descriptive statistics are general psychopathology (p=0.027).
reported as the means and standard deviations for continuous
measurements and as the frequencies and proportions for cat- 4. Discussion
egorical measurements. Demographic and clinical variables
were compared between groups with independent Student’s t- Tis study examined vitamin D levels in minimally treated
tests or chi-squared tests (or Fisher’s exact tests) for con- FEP patients in comparison with MEP in a medium lat-
tinuous and categorical variables, respectively. Correlation itude country. We also assessed the clinical symptoms in
analyses were performed with Pearson correlation coe - cients. FEP and the correlations of vitamin D concentrations with
Te Kolmogorov-Smirnov test was used to con rm the normal positive, negative, and depressive symptoms and general
distributions of the variables. Multiple linear regression was psychopathology. Our main ndings were the following:
used to assess the relationships between the independent (1) we found no signi cant di erence in vitamin D levels
variables (the depressive, positive, and negative symptoms and between the FEP and MEP samples; (2) even in a country
general psychopathology) and the dependent variable (2 - with a signi cant exposure to sunlight, both the FEP and
hydroxyvitamin D). Clinical assessments were performed on MEP groups exhibited low levels of vitamin D; and ( )
the same day as blood sampling. All evalua-tions were vitamin D levels were inversely correlated with general
performed when the clinical picture of FEP had su cient psychopathology in FEP.
stability to warrant collaboration by the patient. A p value <0.0 To our knowledge, only two other studies have examined
was considered to be statistically signi cant. the correlation between vitamin D and psychotic and/or a
ective symptoms in FEP. Graham et al. (201 ) found that
3. Results greater severities of negative symptoms are correlated with
lower vitamin D levels but not with depressive or overall
3.1. Comparison of the Demographics and Vitamin D symptoms in rst-episode schizophrenia patients in North
Levels between the Samples. Overall, patients with FEP and Carolina, USA [20]. Tere was no signi cant di erence in the
patients with MEP were enrolled. Only 1 patient in FEP mean vitamin D level between patients with schizophrenia and
group was excluded because the diagnosis of organic healthy controls [20]. More recently, Yee et al. (201 ) found an
psychosis was made. Descriptions of the participants and association between low bioavailable vitamin D and negative
comparisons between the two groups are summarized in symptoms in FEP in Singapore [2 ]. We did not nd
Table 1. Tere were no signi cant di erences in gender, correlations in the multiple linear regression between vitamin
ethnicity, tobacco use, diagnoses, body mass index (BMI), D and negative symptoms as reported in these two previously
or blood collection season between the two groups. mentioned studies. It is possible that our results were limited
As expected, the FEP sample was signi cantly younger by the lower levels of vitamin D compared with those
than the MEP sample (mean 1.21 vs. 41.1 years; p<0.001). observed in the study published by Graham and colleagues
Te mean vitamin D levels were similar between the two [20].
groups (mean 18.1 ± 7.48 ng/mL for the FEP group and 1 Moreover, studies of chronic schizophrenia patients
.20 ± 11.29 ng/mL for the MEP group; p=0.409). On the revealed associations of vitamin D with depressive and nega-
FEP group, 2 (7 .7 %) patients were medicated tive symptoms. Positive associations of low levels of vitamin
4 Psychiatry Journal

T 1: Demographic and clinical characteristics of the study samples.

FEP (n= ) MEP (n= ) P

Age (years), mean (SD) 1.21 (10.0 ) 41.1 (9.88) <0.001†
Gender, n (%)
Male 2 ( 9.70%) 2 ( 9.70%) 1.000‡
Female 10 ( 9. 0%) 10 ( 9. 0%)
Ethnicity, n (%)
White 2 (9 .97%) 2 (9 .97%) 1.000‡
Black 1 ( .0 %) 1 ( .0 %)
Education (years), mean (SD) 10.28 ( .40)
Marital status, n (%)
Single/divorced 7 (21.21%) 7 (21.21%) 1.000‡
Married/partner 2 (78.78%) 2 (78.78%)
Blood collection season, n (%)
Summer season 1 (48.48%) 11 ( . %) 0.211‡
Winter season 17 ( 1. 1%) 22 ( . %)
Tobacco, n (%)
Yes 14 (42.42%) 19 ( 7. 7%) 0.218‡
No 19 ( 7. 7%) 14 (42.42%)
Weight (kg), mean (SD) 70.8 (14. 7) 74.8 (14.11) 0.2 7†
BMI (kg/m2), mean (SD) 2 .8 (4.12) 2 .08 ( .92) 0.221†
Diagnosis, n (%)
§
Schizophrenia 12 ( . %) 19 ( 7. 8%) 0.148
Delusional disorder (1 .1 %) 2 ( .0 %)
Psychosis NOS 7 (21.21%) 1 ( .0 %)
Bipolar disorder 2 ( .0 %) 4 (12.12%)
Psychotic depression 4 (12.12%) 2 ( .0 %)
Cannabis induced psychosis 2 ( .0 %) (9.09%)
Schizo-a ective disorder 1 ( .0 %) 2 ( .0 %)
Cannabis use, n (%)
Yes (18.18%)
Duration of untreated psychosis (DUP) (days), mean (SD) 4 0. 4 (9 2. 4)
Global Assessment Functioning (GAF), mean (SD) 9.21 (9.44)
Medication Adherence Rating Scale (MARS), Mean (SD) .40 (2.14)
Depressive symptom score (BDI), Mean (SD) 12.42 (9.10)
Positive symptom subscale score (PANSS), Mean (SD) 12.84 ( . 7)
Negative symptom subscale score (PANSS), Mean (SD) 1 .09 (7.27)
General psychopathology subscale score (PANSS), Mean (SD) 1. 9 (7.4 )
†Student’s t-test
‡Chi-squared test
§
Fisher’s exact test

T 2: Correlations between vitamin D levels and clinical variables in rst-episode psychosis.

2 -Hydroxyvitamin D
Simple Multiple
correlation linear regression
r P ß P
Positive Symptoms -0.1 0. 8 0.04 0.79
Negative symptoms -0.480 0.00 ∗ -0.2 9 0.178
General psychopathology -0. 9 0.001∗ -0. 8 0.027∗∗
Depressive symptoms -0.484 0.004∗ 0.22 0.2 7
∗signi cant at p<0.01; ∗∗signi cant at p<0.0 .
Psychiatry Journal

D with negative [17, 18, 1, 2] and depressive symptoms a randomized open-label trial that includes patients with
[18] have been found in chronic psychotic patients, schizophrenia and schizo-a ective disorder and low levels
particularly those with schizophrenia. of vitamin D (< 0 ng/mL) who will be treated with vitamin
Te results of our research demonstrate that vitamin D de D supplementation. Unfortunately, there is no ongoing trial
ciency is present in psychotic disorders even in the early that includes rst-episode psychosis patients. Currently,
phases of the disorder and in countries with regular sunlight there is not su cient evidence to support vitamin D
exposure throughout the year. Te main question persists: is screening and supplementation for psychotic patients.
vitamin D de ciency the cause and/or consequence of the Several limitations of our study exist. First, the relatively
psychotic disorder? Our results indicate that vitamin D could small sample size could limit the generalization of the data,
have an etiological role in some psychopathological symptoms even though our sample is larger than those of previously
of psychosis, and thus its de ciency is present in the early published papers in this eld of knowledge. Second, the cross-
stages of the disorder. For example, due to the neuroprotective sectional design precludes the ability to provide evidence of a
function of vitamin D that prevents oxidative stress in the causal relationship between low levels of vitamin D and
central nervous system, there is a hypothesis that suggests that symptoms in FEP. Tird, we did not control for confounding
oxidative stress resulting from vitamin D de ciency causes factors (e.g., daily calcium intake or sun exposure), which
negative symptoms due to an imbalance in glutamate-GABA might have in uenced our ndings. Fourth, the self-report nature
responses [ , 4]. Vitamin D is also associated with depression of some of the scales and data, namely, the socially
because it is a regulator of serotonin synthesis [ ]. In the undesirable behaviors, such as cannabis use or tobacco smok-
current research, we only found a negative correlation between ing, may be subject to reporting bias. Moreover, the informa-
vitamin D status and the general psychopathology subscale of tion regarding the self-reported psychiatric symptoms (e.g.,
the PANSS. Tis subscale includes a variety of psychiatric depressive symptoms) may not have been accurate. Fi h, we
symptoms, such as depressive, anxious, and physical did not include a healthy control group, which would have
symptoms. Contrary to the previously mentioned studies, we helped to di erentiate whether low levels of vitamin D are
did not nd any signi cant correlation between vitamin D and mainly found in patients with psychiatric disorders or if they
negative symptoms in FEP. Independently of the type of are also found in the general population. Sixth, the
symptoms found to be asso-ciated, vitamin D de ciency has generalization of our ndings to countries of di erent latitudes
been found to be associated with severe psychiatric symptoms and consequently di erent levels of sun exposure and di erent
in all studies, including ours. Some authors also speculate that vitamin D levels must be performed cautiously.
patient behaviors that result from negative symptoms and are
present in all phases of the disorder, including the prodrome,
originate from long periods of time spent indoors without 5. Conclusion
sunlight exposure that result in low levels of vitamin D [ ]. In conclusion, there is evidence demonstrating that there
are low levels of vitamin D in psychotic disorders begin-
Recently a published article from Eyles and colleagues ning in the early stages and that vitamin D could have a
studied the association between neonatal vitamin D status pathophysiological role in psychosis. Te results of research,
and risk of schizophrenia in a large Danish case-control including ours, demonstrate the correlation between low
study, including 2 02 neonates [ 7]. Results showed that levels of vitamin D and high severity of psychiatric
those in the lowest quintile (<20.4noml/L) had an increased
symptoms in all stages of psychotic disorders. Tere are
risk of schizophrenia. Tis is an argument in line with the
ongoing trials that are evaluating vitamin D as a possible
neu-rodevelopment hypothesis of schizophrenia, where
adjuvant treatment in chronic multiepisode psychotic
vitamin D de ciency in early phases of life could also
patients with low levels of vitamin D. In the future, these
represent a risk factor for schizophrenia later.
trials should also include rst-episode psychosis patients.
Research indicates the existence of a preliminary evidence
that certain vitamin and mineral supplements may reduce
psychiatry symptoms in some people with schizophrenia [ 8]. Data Availability
Tis includes vitamin B supplementation, but not vitamin D yet.
Based in our results, vitamin D de ciency could represent a Te SPSS data used to support the ndings of this study are
modi able factor of psychopathology in psychosis and could available from the corresponding author upon request.
condition the clinical picture. Vitamin D as an add-on
treatment could be recommended for patients with low levels.
Evidence in favor of this treatment might soon be provided by Disclosure
the nal results of the two trials (Clin-icalTrials.gov Identi ers: All costs relating to the completion of this study were
NTC017 948 and NCT011 9142). One is a randomized, double
covered by personal funds from both authors.
blind placebo-controlled trial of which the main objective is to
evaluate the e ect of vitamin D supplementation on the mental
states of clozapine-treated patients with chronic schizophrenia Conflicts of Interest
and vitamin D de ciency (20- 0 ng/mL) and the relation of
disease severity with serum vitamin D level. Te second study Te authors declare that there are no con icts of interest
is regarding the publication of this paper.
 Psychiatry Journal

Acknowledgments [1 ] J. J. McGrath, “Te surprisingly rich contours of schizophrenia

epidemiology,” Archives of General Psychiatry, vol. 4, no. 1,
Te authors are grateful for the collaboration of Dr. Luis Silva, pp. 14–1 , 2007.
Director of the Pathology Department of the Hospital Vila [17] R. N. Yuksel,¨ N. Altunsoy, B. Tikir et al., “Correlation between
Franca de Xira, for his contribution to this research project. total vitamin D levels and psychotic psychopathology in patients
with schizophrenia: therapeutic implications for add-on vitamin
D augmentation,” Terapeutic Advances in Psy-chopharmacology,
References vol. 4, no. , pp. 2 8–27 , 2014.
[1] B. Wharton and N. Bishop, “Rickets,” Te Lancet, vol. 2, no. 9 [18] M. Nerhus, A. O. Berg, L. R. Kvitland et al., “Low vitamin D
9 , pp. 1 89–1400, 200 . is associated with negative and depressive symptoms in
[2] G. Valipour, P. Saneei, and A. Esmaillzadeh, “Serum vitamin psychotic disorders,” Schizophrenia Research, vol. 178, no.
D levels in relation to schizophrenia: a systematic review and 1- , pp. 44–49, 201 .
meta-analysis of observational studies,” Te Journal of [19] M. Crews, J. Lally, P. Gardner-Sood et al., “Vitamin D de
Clinical Endocrinology & Metabolism, vol. 99, no. 10, ciency in rst episode psychosis: A case-control study,”
Article ID jc20141887, pp. 8 – 872, 2014. Schizophrenia Research, vol. 1 0, no. 2- , pp. – 7, 201 .
[ ] K. E. Fuller and J. M. Casparian, “Vitamin D: Balancing cuta- [20] K. A. Graham, R. S. Keefe, J. A. Lieberman, A. S. Calikoglu, K.
neous and systemic considerations,” Southern Medical M. Lansing, and D. O. Perkins, “Relationship of low vitamin D
Journal, vol. 94, no. 1, pp. 8– 4, 2001. status with positive, negative and cognitive symptom domains in
[4] E. Hypponen¨ and C. Power, “Hypovitaminosis D in British people with rst-episode schizophrenia,” Early Intervention in
adults at age 4 y: nationwide cohort study of dietary and Psychiatry, vol. 9, no. , pp. 97–40 , 201 .
lifestyle predictors,” American Journal of Clinical Nutrition, [21] M. Nerhus, A. O. Berg, S. R. Dahl et al., “Vitamin D status in
vol. 8 , no. , pp. 8 0–8 8, 2007. psychotic disorder patients and healthy controls - Te in uence
[ ] L. Ford, V. Graham, A. Wall, and J. Berg, “Vitamin D concentra- of ethnic background,” Psychiatry Research, vol. 2 0, no. 2,
tions in an UK inner-city multicultural outpatient population,” pp. 1 – 21, 201 .
Annals of Clinical Biochemistry, vol. 4 , no. , pp. 4 8–47 , 200 . [22] J. Salavert, D. Grados, N. Ramiro et al., “Association between
[ ] M. F. Holick, “Vitamin D de ciency,” Te New England vitamin D status and schizophrenia,” Te Journal of Nervous and
Journal of Medicine, vol. 7, no. , pp. 2 –281, 2007. Mental Disease, vol. 20 , no. , pp. 409–412, 2017.
[7] M. S. Johnsen, G. Grimnes, Y. Figenschau, P. A. Torjesen, B. [2 ] J. Y. Yee, Y. M. See, N. A. Abdul Rashid, S. Neelamekam,
Almas, and R. Jorde, “Serum free and bio-available 2 - and J. Lee, “Association between serum levels of bioavailable
hydroxyvitamin D correlate better with bone density than serum vitamin D and negative symptoms in rst-episode psychosis,”
total 2 -hydroxyvitamin D,” Scandinavian Journal of Clinical & Psychiatry Research, vol. 24 , pp. 90– 94, 201 .
Laboratory Investigation, vol. 74, no. , pp. 1–7, 2014. [24] R. D. Sheth, “Metabolic concerns associated with
[8] A. Zadshir, N. Tareen, D. Pan, K. Norris, and D. Martins, “Te antiepileptic medications,” Neurology, 2012.
prevalence of hypovitaminosis D among US adults: Data [2 ] S. P. Singh, J. E. Cooper, H. L. Fisher et al., “Determining the
from the NHANES III,” Ethnicity & Disease, vol. 1 , chronology and components of psychosis onset: the
supplement , no. 4, 200 . nottingham onset schedule (NOS),” Schizophrenia Research,
[9] J. Wortsman, L. Y. Matsuoka, T. C. Chen, Z. Lu, and M. F. Holick, vol. 80, no. 1, pp. 117–1 0, 200 .
“Decreased bioavailability of vitamin D in obesity,” American [2 ] P. McGu n, A. Farmer, and I. Harvey, “A polydiagnostic
Journal of Clinical Nutrition, vol. 72, no. , pp. 90– 9 , 2000. application of operational criteria in studies of psychotic illness.
[10] E. Cutillas-Marco, A. Fuertes-Prosper, W. B. Grant, and M. Development and reliability of the OPCRIT system,” Archives of
Morales-Suarez´-Varela, “Vitamin D de ciency in South Europe: General Psychiatry, vol. 48, no. 8, pp. 7 4–770, 1991.
e ect of smoking and aging,” Photodermatology, Photoimmunol- [27] S. R. Kay, A. Fiszbein, and L. A. Opler, “Te positive and
ogy & Photomedicine, vol. 28, no. , pp. 1 9–1 1, 2012. nega-tive syndrome scale (PANSS) for schizophrenia,”
[11] A. P. Hermann, C. Brot, J. Gram, N. Koltho , and L. Mosek- Schizophrenia Bulletin, vol. 1 , no. 2, pp. 2 1–27 , 1987.
ilde, “Premenopausal smoking and bone density in 201 peri- [28] A. T. Beck, R. A. Steer, and G. K. Brown, “Manual for the
menopausal women,” Journal of Bone and Mineral Research, beck depression inventory-II,” TX Psychological
vol. 1 , no. 4, pp. 780–787, 2000. Corporation, pp. 1– 82, 199 .
[12] M. Wrzosek, J. Lukaszkiewicz, M. Wrzosek et al., “Vitamin [29] A. V. Serra and J. P. Abreu, “Aferic¸ao˜ dos quadros cl´ınicos
D and the central nervous system,” Pharmacological Reports, depressivos. I-Ensaio de aplicac¸ao˜ do ‘Inventario´
vol. , no. 2, pp. 271–278, 201 . Depressivo de Beck’a uma amostra Portuguesa de doentes
[1 ] J. McGrath, K. Saari, H. Hakko et al., “Vitamin D supplemen- deprimidos,” Coimbra Medica´ XX, pp. 2 – 44, 197 .
tation during the rst year of life and risk of schizophrenia: a [ 0] K. Tompson, J. Kulkarni, and A. A. Sergejew, “Reliability and
Finnish birth cohort study,” Schizophrenia Research, vol. 7, validity of a new medication adherence rating scale (MARS)
no. 2- , pp. 2 7–24 , 2004. for the psychoses,” Schizophrenia Research, vol. 42, no. , pp.
[14] E. F. Torrey, B. B. Torrey, and M. R. Peterson, “Seasonality 241– 247, 2000.
of schizophrenic births in the United States,” Archives of [ 1] R. C. W. Hall, “Global assessment of functioning. A modi ed
General Psychiatry, vol. 4, no. 9, pp. 10 –1070, 1977. scale,” Psychosomatics, vol. , no. , pp. 2 7–27 , 199 .
[1 ] J. J. McGrath, T. H. Burne, F. Feron,´ A. MacKay-Sim, and [ 2] S. D. Bulut, S. Bulut, D. G. Atalan et al., “Te relationship
D. W. Eyles, “Developmental vitamin D de ciency and risk of between symptom severity and low Vitamin D levels in
schizophrenia: a 10-year update,” Schizophrenia Bulletin, vol. patients with schizophrenia,” PLoS ONE, vol. 11, no. 10,
, no. , pp. 107 –1078, 2010. Article ID e01 284, 201 .
Psychiatry Journal 7

[ ] K. Cieslak, J. Feingold, D. Antonius et al., “Low Vitamin D

levels predict clinical features of schizophrenia,” Schizophrenia
Research, vol. 1 9, no. 2- , pp. 4 – 4 , 2014.
[ 4] Y. Albayrak, C. Unsal, M. Beyazyuz,¨¨ ¨
A. Unal, and M. Kuloglu,ˇ

“Reduced total antioxidant level and increased oxidative stress

in patients with de cit schizophrenia: a preliminary study,”
Progress in Neuro-Psychopharmacology & Biological Psychiatry,
vol. 4 , pp. 144–149, 201 .
[ ] R. P. Patrick and B. N. Ames, “Vitamin D hormone regulates
serotonin synthesis. Part 1: relevance for autism,” Te FASEB
Journal, vol. 28, no. , pp. 2 98–241 , 2014.
[ ] M. Belvederi Murri, M. Respino, M. Masotti et al., “Vitamin D
and psychosis: Mini meta-analysis,” Schizophrenia Research, vol.
1 0, no. 1, pp. 2 –2 9, 201 .
[ 7] D. W. Eyles, M. Trzaskowski, A. A. Vinkhuyzen et al., “Te
association between neonatal vitamin D status and risk of
schizophrenia,” Scienti c Reports, vol. 8, no. 1, 2018.
[ 8] J. Firth, B. Stubbs, J. Sarris et al., “Te e ects of vitamin and
mineral supplementation on symptoms of schizophrenia: A
systematic review and meta-analysis,” Psychological Medicine,
vol. 47, no. 9, pp. 1 1 –1 27, 2017.