Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
...
PMID:Vitamin D insufficiency and schizophrenia risk: evaluation of hyperprolinemia as a mediator of association. 2478 57

Vitamin D deficiency has been linked with schizophrenia. We aimed to determine whether patients with a first episode of psychosis (FEP) had lower vitamin D levels compared with controls considering their final diagnosis. We conducted a cross-sectional study determining 25-hydroxyvitamin D blood levels. 25-Hydroxyvitamin D levels were considered optimum at 20 ng/mL or greater. A group of 45 adult patients with FEP and a group of 22 healthy controls matched for age were recruited. The patient group was subdivided in two final diagnosis groups (schizophrenia versus other psychoses) after a 6-month follow-up. Average vitamin D values were deficient for FEP patients, especially those 22 with a final diagnosis of schizophrenia. These results relating vitamin D and schizophrenia generate interest to further examine this association.
 ...
PMID:Association Between Vitamin D Status and Schizophrenia: A First Psychotic Episode Study. 2896 99