Vitamin D deficiency is common in CF. Given the limited evidence specific to CF, the committee provided consensus recommendations for most of the recommendations. The committee recommends yearly screening for vitamin D status, preferably at the end of winter, using the serum 25-hydroxyvitamin D measurement, with a minimal 25-hydroxyvitamin D concentration of 30 ng/ml (75 nmol/liter) considered vitamin D sufficient in individuals with CF. Recommendations for age-specific vitamin D intake for all individuals with CF, form of vitamin D, and a stepwise approach to increase vitamin D intake when optimal vitamin D status is not achieved are delineated.

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 catalyses 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 can not 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.

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 136 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

OBJECTIVE: 7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differences in the age of study participants and duration of illness. This study is the first to report novel longitudinal patterns in young adulthood from both physiological and pathological viewpoints using 7T MRS. METHODS: Utilizing a four-year longitudinal cohort with 38 first episode psychosis (FEP) patients (onset within 2 years) and 48 healthy controls (HC), the authors examined the annual percentage changes of 9 neurometabolites in 5 brain regions. RESULTS: Both FEP patients and HC subjects were found to have significant longitudinal reductions in glutamate (Glu) in the anterior cingulate cortex (ACC). Only FEP patients were found to have a significant decrease over time in gamma-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mI), and total choline (tCho: phosphocholine plus glycerophosphocholine) in the ACC. Uniquely, glutathione (GSH) was found to have a near zero annual percentage change in both FEP patients and HC subjects in all 5 brain regions over a four-year timespan in young adulthood. CONCLUSIONS: GSH could be a trait marker for diagnostic applications at least in young adulthood. Glu, GABA, NAA, mI, and tCho in the ACC are associated with the patient's status and could be state markers for mechanistic studies of psychotic disorders, including those for progressive pathological changes and medication effects in young adulthood.