The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings.In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status.Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity.Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.
Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.
Background As trimethylamine-N-oxide (TMAO) is considered to be associated with various diseases, rapid determination of serum TMAO concentration is of clinical interest. This study is aimed at evaluating the analytical performance of a simple isocratic liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for TMAO quantification. Methods TMAO measurements were performed on a tandem mass spectrometer, SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA), coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies, Santa Clara, CA, USA). The separation was performed on a Hypercarb Porus Grahitic Carbon (PGC) column (ThermoFisher Scientific, Waltham, MA, USA) by isocratic elution mode. Linearity, precision, recovery, and pre-analytical requirements of the TMAO LC-MS/MS method were evaluated. The imprecision acceptance criteria were defined 15%. We investigated sample stability at room temperature (RT) and assessed the serum TMAO concentrations of 188 healthy adults. Results The TMAO LC-MS/MS method was linear over the concentration range of 0.5 - 80 μmol/L. Intra- and inter-day precision ranged between 2.24 - 3.37% and 6.95 - 9.97%, recovery between 106 - 114%, respectively. At RT, serum samples were stable for 8 days. The median serum TMAO concentration of 188 healthy adults was 2.27 μmol/L (2.5th and 97.5th percentile: 0.75 - 10.46 μmol/L), respectively. Conclusions The isocratic TMAO LC-MS/MS shows a broad analytical range and meets the imprecision acceptance criteria of 15%. This method is a robust and reliable diagnostic tool for the assessment of the human TMAO status. Serum samples are stable at RT for at least 8 days.
Vitamin D is a well-established regulator of calcium and phosphate metabolism that has neurotrophic and neuroprotective properties. Deficiency of vitamin D has been proposed to promote cognitive dysfunction and brain atrophy. However, existing studies provide inconsistent results. Here we aimed to investigate the association between vitamin D metabolites, cognitive function and brain atrophy in a cohort of well-characterized community-dwelling elderly individuals with normal neurological status and without history of stroke and dementia.25(OH)D3, 25(OH)D2 and 24,25(OH)2D3 were measured by liquid-chromatography tandem mass-spectrometry in serum samples from 390 community-dwelling elderly individuals. All participants underwent thorough neuropsychiatric tests capturing memory, executive function and visuopractical skills. In 139 of these individuals, MRI of the brain was performed in order to capture neurodegenerative and vascular changes.Total 25(OH)D (ß=0.003, 0.037), 24,25(OH)2D3 (ß=0.0456, p=0.010) and vitamin D metabolite ratio (VMR) (ß=0.0467, p=0.012) were significantly related to memory function. Adjustment for multiple testing weakened these relationships, but trends (p≤0.10) remained. 24,25(OH)2D3 and VMR showed similar trends also for visuopractical skills and global cognitive function. No significant relationships existed between vitamin D metabolites and MRI derived indices of neurodegeneration and vascular changes. Sub-group analyses of individuals with low concentrations of 25(OH)D and 24,25(OH)2D3 showed significantly worse memory function compared to individuals with normal or high concentrations.Vitamin D deficient individuals appear to have a modest reduction of memory function without structural brain atrophy. Future studies should explore if vitamin D supplementation can improve cognitive function.
Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD).
