Article

Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study

Center for Innovation in Pediatric Practice, The Research Institute at Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA. .
BMC Psychiatry (Impact Factor: 2.24). 05/2012; 12(1):38. DOI: 10.1186/1471-244X-12-38
Source: PubMed

ABSTRACT 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.
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.
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 1.1‒13.4; p < 0.04). Race was no longer associated with psychosis when the results were adjusted for vitamin D level.
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.

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    • "Much of the epidemiological and experimental basis underlying vitamin D risk comes from study of the developing embryo or early infant. Although a recent cross-sectional study reported the significant association of insufficiency with psychotic features in adolescents (ages 12–18) (Gracious et al., 2012), to our knowledge only one study has explored dietary provided vitamin D and risk of psychotic symptoms in adults (Hedelin et al., 2010). Therefore, further study of hyperprolinemia and vitamin D in neonates and children, as well as those at-risk prior to symptom onset, is warranted to fully explore the timing of vitamin D insufficiency exposure, proline elevation, psychotic symptom onset, and the relationship with schizophrenia. "
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    ABSTRACT: 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.
    Schizophrenia Research 06/2014; 156(1). DOI:10.1016/j.schres.2014.03.017 · 4.43 Impact Factor
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    • "Among these, 7 studies were eligible for the meta-analysis. Four studies were excluded the age of participants, higher in one study (Lapid et al., 2013) and lower in three other studies (Bonnot et al., 2011; Gracious et al., 2012; Tolppanen et al., 2012). Four other studies were excluded because data did not allow the calculation of an effect size: data was not reported (McGrath et al., 2001), there was an insufficient number of cases (Dealberto, 2013) or VD levels were not normally distributed (Schneider et al., 2000; Humble et al., 2010). "
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    ABSTRACT: Individuals with psychotic disorders are more likely to have vitamin D (VD) deficiency, while evidence suggests VD could have pathophysiological roles. We summarized meta-analytically the available evidence on VD levels in psychotic disorders in comparison with healthy controls and other psychiatric illnesses. We found seven studies, all reporting insufficient VD levels in patients with psychosis. Schizophrenia had a medium effect size for lower VD than healthy controls, and a trend for lower levels than other psychoses. There were non-significant differences between schizophrenia and major depression. No study has investigated the potential psychotropic effects of VD supplementation in patients with psychosis.
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    • "Among these, 7 studies were eligible for the meta-analysis. Four studies were excluded the age of participants, higher in one study (Lapid et al., 2013) and lower in three other studies (Bonnot et al., 2011; Gracious et al., 2012; Tolppanen et al., 2012). Four other studies were excluded because data did not allow the calculation of an effect size: data was not reported (McGrath et al., 2001), there was an insufficient number of cases (Dealberto, 2013) or VD levels were not normally distributed (Schneider et al., 2000; Humble et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals with psychotic disorders are more likely to have vitamin D (VD) deficiency, while evidence suggests VD could have pathophysiological roles. We summarized meta-analytically the available evidence on VD levels in psychotic disorders in comparison with healthy controls and other psychiatric illnesses. We found seven studies, all reporting insufficient VD levels in patients with psychosis. Schizophrenia had a medium effect size for lower VD than healthy controls, and a trend for lower levels than other psychoses. There were non-significant differences between schizophrenia and major depression. No study has investigated the potential psychotropic effects of VD supplementation in patients with psychosis.
    Schizophrenia Research 07/2013; 150(1). DOI:10.1016/j.schres.2013.07.017 · 4.43 Impact Factor
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