Vitamin D Levels in Lebanese Patients with Schizophrenia: A Case-Control Study

Special Article - Vitamin D Deficiency

Ann Nutr Disord & Ther. 2017; 4(1): 1041.

Vitamin D Levels in Lebanese Patients with Schizophrenia: A Case-Control Study

Haddad C¹, Zoghbi M1,2, Hallit S1,3,4,5, Bou Assi T¹, Medlej-Hashim M6, Nabbout R6,#, Azar J1,7,#,*

¹Psychiatric Hospital of the Cross, Lebanon

²Department of Family Medicine, Saint-Joseph University, Lebanon

³School of Pharmacy, University of Saint Joseph, Lebanon

4University of Saint-Esprit Kaslik, Lebanon

5School of Pharmacy, Lebanese University, Lebanon

6Faculty of Science, Lebanese University, Lebanon

7Department of Medicine, Lebanese American University, Lebanon

#Last co-authors

*Corresponding author: Jocelyne Azar, Department of Medicine, Lebanese American University, Psychiatric Hospital of the Cross, Jall-Eddib, Lebanon

This work has been done in the frame of the “Behavioral and Cognitive Neuroscience Master 2 Program”, Faculty of Sciences, Lebanese University

Received: February 13, 2017; Accepted: March 07, 2017; Published: March 14, 2017


Objectives: To compare the vitamin D status in schizophrenics to that of healthy controls; secondary objectives were to assess the correlation between severe vitamin D deficiency and the severity of schizophrenia symptoms and to evaluate the potential factors influencing this status.

Methods: A case-control study, conducted between March and July 2016, recruited 100 patients with schizophrenia and 100 controls with no known psychiatric disorders and matched for age and sex.

Results: Schizophrenic patients had a more severe vitamin D deficiency compared to healthy controls (9% vs. 3%). Vitamin D insufficiency was found in 28% of schizophrenic patients compared to 37% in healthy controls (p=0.053). BCRS and MRSS scales were significantly associated with a more severe vitamin D deficiency (p=0.006). We couldn’t detect any association between the total PANSS score and its three subscales with vitamin D deficiency (p>0.05). Sun exposure, intermediate and high socioeconomic levels would significantly increase the odds of having an increased level of vitamin D as compared to low socioeconomic level (OR=1.046, OR=141.919 and OR=132.110) respectively. Higher MRSS scores would significantly increase the odds of having a more severe vitamin D deficiency by 15.2% (OR=0.848, CI 0.731 - 0.984, p=0.029).

Conclusion: Vitamin D insufficiency is prevalent in patients with schizophrenia. Further work is needed to answer the question of causality. Is vitamin D deficiency the result or the cause of schizophrenia? Future cohort studies may investigate the association with longer follow-up. Spreading awareness among health care professionals for routine serum vitamin D testing, along with patient education, are necessary to avoid this problem.

Keywords: Vitamin D; Schizophrenia; BCRS; MRSS; Schizophrenia symptoms


Vitamin D deficiency has been extensively linked to a wide range of neuropsychiatric disorders, including schizophrenia [1-4]. In fact, vitamin D is involved in various brain processes including neurodevelopment, neurotransmitter expression, neurotrophic and growth factor regulation and is thought to be neuroprotective [3]. In addition to its well-known role in calcium and bone metabolism, vitamin D has been shown to be a potent inducer of nerve growth factor synthesis [5-7]. McGrath suggested that a prenatal deficiency of vitamin D might be a risk factor for schizophrenia [5].

A pathophysiological effect of vitamin D levels on schizophrenia development, with a reversible effect after correction has been postulated [8]. Studies have shown that schizophrenics tend to be born in winter/spring seasons during which the Ultraviolet rays (UVB) required to synthesize vitamin D are reduced [9,10]. In addition, schizophrenic patients are more likely to stay indoors and have reduced exposure to sunlight, hence the increased risk of low vitamin D level [3,7]. Furthermore, most schizophrenic patients do not consume enough dietary vitamin D [11,12] with the latter shown to reduce the risk of psychosis or schizophrenia [6,13]. These factors may not be causal but may arise due to confusion with independent risk factors [8], such as ethnicity, dietary factors, sedentary lifestyle, physical activity, body mass index, urban living and socioeconomic status [7,8,14,15].

Vitamin D has also been linked to mental illnesses including Alzheimer’s [16], premenstrual mood disorder [17], major depression [18] and psychosis [19]. However, the relationship between vitamin D status and brain functions is still not elucidated [19], despite some evidence of negative, cognitive [20,21] and mood [22] effects in people with insufficient vitamin D levels. A recent study showed that in schizophrenic patients, a significantly greater severity of negative symptoms was correlated with lower vitamin D status, while overall symptom severity and positive symptom severity approached a significant relationship with vitamin D status. These findings lead researchers to hypothesize that inadequate vitamin D status may account for some portion of the symptom burden experienced by schizophrenic persons [1].

Lebanon has a high prevalence of 25(OH)-D deficiency in adults and older adults [23,24] however, data regarding vitamin D levels in psychiatric patients is still lacking. Therefore, the primary objective of this study was to compare the vitamin D status in schizophrenics to that of healthy controls; secondary objectives were to assess the correlation between severe vitamin D deficiency and the severity of schizophrenia symptoms and to evaluate the potential factors influencing this status.

Materials and Methods

Study design and participants

A case-control study was conducted at the Psychiatric Hospital of the Cross (PHC) - Lebanon, between March and July 2016. A hundred patients with schizophrenia and 100 controls with no known psychiatric disorders were recruited and matched for age and sex. The study received approval by the research and ethics committee of the hospital and participants or their legally representative provided a written informed consent before entering the study.

Patients newly admitted to the hospital, suffering from schizophrenia for no longer than ten years, diagnosed by the treating psychiatrist according to medical file diagnosis [25].

Individuals were excluded if they had any other mental illness, had a diagnosis of alcohol or substance dependence, were treated with vitamin D supplement, or had a metabolic disease that may affect serum vitamin D concentrations.

Clinical and psychiatric evaluations

Demographic (age, gender, geographic region, marital status, occupation, educational level, monthly income per house) and clinical information of the participants (diagnosis, duration of illness, medications intake at the time of the study, blood pressure, history of medical illness and family history of mental disorders) were collected from medical files. The socioeconomic status divided into three levels (low (<1000USD), intermediate (1000-2000USD), high (>2.000USD), was collected from medical files based on the income, education and occupation of each patient. The number of weekly hours of sun exposure, physical activities (indoor and outdoor) and consumption of certain foods (milk, fish, eggs, meat, fruits and vegetables) were also obtained from all participants via a face-to-face interview by 3 investigators. The Body Mass Index (BMI) was calculated as weight (in kilograms) divided by the square of height (in meters) and classified according to WHO (World Health Organization) classification [26]. Underweight (<18.5), Normal (18.5-24.9), Overweight (25.0-29.9) and Obese (= 30.0) [26].

Two psychologists performed all the diagnostic assessments of symptoms and functioning using the Positive and Negative Syndrome Scale for schizophrenia (PANSS) [27], the Brief Cognitive Rating Scale (BCRS) [28] and the Morningside Rehabilitation Status Scale (MRSS) [29]. Briefly, the PANSS is used for measuring symptom severity in patients with schizophrenia and evaluating positive and negative symptoms of psychotic disorders [27]. The BCRS describes the severity of cognitive impairment providing five main axes (concentration, short term memory, long term memory, orientation, and self-care ability) and five co-axes (language, psychomotor, mood and behavior, drawing skills, calculating skills) each rated on a 7-step scale (1=no impairment; 7=most severe impairment) [28]. The MRSS scale is used to evaluate the level of general functioning in psychiatric patients. This scale allows the clinician to rate social adaptation of the subject on four axes: dependence/Independence, activity/inactivity level, the level of social integration/ isolation in addition to the effects of present symptoms. Each axis is rated on a 7-step scale, with 0 meaning no disorder and 7 meaning an extreme degree of disability, with higher scores indicating greater dysfunction [29].

Vitamin D measurement blood samples and laboratory analysis

The laboratory analysis was performed at the Laboratory department of the PHC. 6ml of blood were drawn from the antecubital vein of each participant for the measurement of vitamin D. Vitamin D levels (serum 25-hydroxyvitamin D (25 OHD) were determined by chemiluminescence immunoassay (Architect I, Abbott Laboratories).

We divided the Vitamin D level in four groups to take into consideration participants with severe deficiency. These cut-offs were defined almost exclusively based on data from older populations and from western countries [30].

Statistical analysis

Statistical Package for the Social Sciences (SPSS) 22 was used for the data analysis. Student’s t-test was used to compare continuous variables in two groups. Pearson correlation was used for linear correlation between continuous variables. For categorical variables, the χ2 and Fisher exact tests were used. Multivariate analysis logistic regressions were carried out using variables that showed a p-value <0.2 in the bivariate analysis.

A backward logistic regression test was performed to identify the independent variables that affect 25(OH) D levels. Vitamin D variable categorized into two groups (Vitamin D<25nmol/l, Vitamin D>25nmol/l) [31,32] were used as dependent variables. Significance will be defined as a p-value less than 0.05 levels.


Sociodemographic characteristics of the study sample

Overall 200 participants were enrolled. The mean age of schizophrenic patients was 37.00 ± 11.65 years compared to 38.77±10.61 years for the controls (age ranging between 18 and 65 years for the whole sample). Most of the participants were male in each group (72% in control group, 70% in cases group). The majority of cases were single (76%), having an intermediate and below level of education (60%), and a low socioeconomic level (54%). On the other hand, 44% of the control group was single, 60% had secondary and high levels of education and the majority of them had an intermediate socio-economic level (76%). More than half of the patients were smokers (60%) versus 48% of the controls.

Most of the patients didn’t have a history of medical illness (71%) and 42% of them had a family history of mental disorders, while all controls didn’t have a family history of mental disorders 100% and almost all of them 88% didn’t have a history of medical illness.

Almost half of the patients had normal BMI (48%), with 52% being overweight or obese, while most of the controls were overweight and obese (62%) and 38% having normal BMI.

A significant difference between the two groups was found for the geographic region, marital status, education level, socioeconomic level, history of medical illness, family history of psychiatric illness (p<0.005).

Comparison of vitamin D category between schizophrenic patients and healthy control

Figure 1 shows the percentage of vitamin D level categorized according to IOM guideline between schizophrenic patients and healthy control. The results showed that 9% of schizophrenic patients had a severe vitamin D deficiency as compared to 3% in the control group. Almost half of the schizophrenic patients (49%) had vitamin D deficiency compared to 54% in healthy controls. Vitamin D insufficiency was found in 28% of schizophrenic patients compared to 37% in healthy controls, while vitamin D sufficiency was found in 14% of schizophrenic patients compared to 6% in healthy controls. The difference in vitamin D categories between controls and schizophrenics tended to significance (p=0.053).