Ya-Qiong Liu

Correlations of Trace Element Levels in the Diet, Blood, Urine, and Feces in the Chinese Male

In order to explore the associations between trace elements in dietary intake and the other three biological media (blood, urine, or feces) and inter-element interactions among the latter, we simultaneously collected 72-h diet duplicates, whole blood, and 72-h urine and feces from 120 free-living healthy males in China. Correlations among the toxic (cadmium [Cd], lead [Pb]), and nutritionally essential (zinc [Zn], copper [Cu], iron [Fe], manganese [Mn], selenium [Se], iodine [I]) elements were evaluated using Spearman rank correlation analysis based on analytical data determined by inductively coupled plasma-mass spectrometry. Dietary Cd intakes were highly correlated with the fecal Cd and blood Cd levels. Inverse correlations were found for Fe–Cd and Fe–Pb in both diet versus blood and diet versus feces. Cd–Zn and Cd–Se were significantly directly correlated in the urine and feces. Cd–Se and Pb–Se were negatively correlated in blood. In addition, there existed an extremely significant association between urinary Se and urinary I. Moreover, the other two highly direct correlations were found for Se–Fe and for I–Fe in urine. Improved knowledge regarding their mutual associations is considered to be of fundamental importance to understand more the complex interrelationships in trace element metabolism.

Association of essential trace metals in maternal hair with the risk of neural tube defects in offspring.

BACKGROUND The relationship between essential trace metals (ETMs) and the risk of neural tube defects (NTDs) is still unclear. One of the challenges is to evaluate the intake of ETMs of women during their early period of pregnancy. We proposed the hypothesis that an ETM deficiency in women during their early period of pregnancy is associated with an elevated risk of NTDs in offspring. METHODS We recruited 191 women with NTD-affected pregnancies (case group) and 261 women who delivered healthy infants (control group). Nine ETMs in hair sections grown during maternal early pregnancy were analyzed: iron (Fe), zinc (Zn), copper (Cu), cobalt (Co), manganese (Mn), chromium (Cr), nickel (Ni), molybdenum (Mo), and stannum (Sn). Information on maternal dietary habits were collected by questionnaire. RESULTS We observed a significant decreasing trend in the dose-response relationships between the Ni and Mo concentrations in hair and NTD risks. A Zn deficiency was only associated with an elevated risk of spina bifida, and a Sn deficiency was only associated with anencephaly. The Ni and Zn concentrations in hair were positively correlated with the frequency of consumption of fresh green vegetables and fresh fruits, while the Zn concentration was also associated with fish or meat consumption. CONCLUSION We concluded that maternal intakes of the four ETMs (Ni, Mo, Zn, and Sn) played an important role in the formation of NTDs in our study population, and that this intake is related to maternal dietary habits.Birth Defects Research 109:234-243, 2017.© 2016 Wiley Periodicals, Inc.

Meta-Analyses of Manganese Superoxide Dismutase Activity, Gene Ala-9Val Polymorphism, and the Risk of Schizophrenia.

AbstractSchizophrenia is a complex and disabling psychiatric disorder, and tardive dyskinesia (TD) is a severe adverse drug effect occurring in 20% to 40% of schizophrenic patients chronically treated with typical neuroleptics. Previous studies suggested that the manganese superoxide dismutase (MnSOD) activity was associated with the development of schizophrenia. Ala-9Val polymorphism, a functional polymorphism of MnSOD gene, has been reported to be related to the risk of schizophrenia and TD. However, these studies did not lead to consistent results. We performed meta-analyses aiming to assess the association between MnSOD activity and schizophrenia, as well as the association of MnSOD Ala-9Val polymorphism with schizophrenia and TD in schizophrenic patients.We search for the literature on MnSOD and schizophrenia in English or Chinese published up to May 1, 2015 on PubMed, EMBASE, the Cochrane Databases, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by consensus with a third reviewer. Data were pooled using fixed-effect or random-effect models. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the MnSOD activity. Pooled odds ratio (OR) and 95% CI were calculated for Ala-9Val genotype and allele frequencies.There were 6, 6, and 10 studies entering 3 parts of meta-analyses, respectively. The MnSOD activity of patients was significantly lower than that of controls (SMD = −0.94; 95% CI: −1.76, −0.12; P = 0.025). No significant associations of Ala-9Val genotypes (OR = 1.14; 95% CI: 0.97, 1.33; P = 0.109) and alleles (OR = 1.06; 95% CI: 0.94, 1.20; P = 0.361) with the risk of schizophrenia were observed. We also did not reveal significant associations of the genotypes (OR = 0.82; 95% CI: 0.66, 1.02; P = 0.075) and alleles (OR = 0.90; 95% CI: 0.76, 1.06; P = 0.215) with the risk of TD in schizophrenia.The decreased MnSOD activity may be associated with the risk of chronic schizophrenia in Chinese population, while MnSOD Ala-9Val polymorphism may not play a significant role in the development of schizophrenia and TD. Longitudinal studies with larger sample sizes and different ethnicities are needed to confirm the association of the MnSOD Ala-9Val variants with schizophrenia and TD.

Association on DISC1 SNPs with schizophrenia risk: A meta-analysis

Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological etiologies. Although DISC1 gene has been shown as a risk factor for schizophrenia in some reports, there is a lack of a consensus. We therefore performed separate meta-analyses aiming to assess the associations between DISC1 SNPs and schizophrenia risk. We found that SNP rs821597 is significantly associated with schizophrenia risk in terms of both allelic and genotypic distribution, while SNP rs821616 is associated with schizophrenia in terms of genotypic distribution, especially in cases above 40 years old.

Unbiased lipidomic profiling reveals metabolomic changes during the onset and antipsychotics treatment of schizophrenia disease

IntroductionSchizophrenia (SCH) is one of the most common psychiatric disorders, which involves impairments in motivation and cognition. The pathological mechanisms underlying SCH are still unknown, and no effective therapies can prevent or treat perfectly the cognitive impairments and deficit symptoms caused by SCH.ObjectivesWe aimed to find the lipid expression change in plasma that underlie SCH onset and antipsychotics treatment.MethodsWe performed a data independent acquisition-based untargeted lipidomic approach on a quadrupole-time of flight liquid chromatography coupled to mass spectrometry platform. The plasma lipidomic profiles of SCH patients (n = 20) pre- and post-antipsychotics treatment were acquired as well as healthy controls (n = 29). Grouped or paired t-test were used to analyze the data.ResultsOver 1000 features were detected by our lipidomic analysis, of which 445 lipids belonging to 17 lipid species were reliably identified by tandem mass spectrometry. After statistical analysis, 47 lipids belonging to 9 lipid species were found to be dysregulated between naive SCH patients and healthy controls, and 50 lipids belonging to 9 lipid species were found to be dysregulated after antipsychotics treatment. These findings include several new SCH-relevant lipid species such as sphingomyelin, acylcarnitine and ceramide. Four types of lipid expression regulative patterns can be concluded from the above mentioned findings, revealing information about mechanism, side-effect and potential target of antipsychotics.ConclusionsThe work presented here have revealed several new lipid species which are significantly dysregulated in SCH disease development or antipsychotics treatment. These lipids provide new evidence for the pathological studies of SCH and new antipsychotics development, or can be considered as potentially candidate biomarkers for further validation.

Alterations of eicosanoids and related mediators in patients with schizophrenia

Schizophrenia (SCZ) is a multifactorial psychiatric disorder. Currently, its molecular pathogenesis remains largely unknown, and no reliable test for diagnosis and therapy monitoring is available. Polyunsaturated fatty acids (PUFAs) and their derived eicosanoid signaling abnormalities are relevant to the pathophysiology of schizophrenia. However, comprehensive analysis of eicosanoids and related mediators for schizophrenia is very rare. In this study, we applied a targeted liquid chromatography-mass spectrometry based method to monitor 158 PUFAs, eicosanoids and related mediators from enzyme-dependent or independent pathways, in the serum samples of 109 healthy controls, and 115 schizophrenia patients at baseline and after an 8-week period of antipsychotic therapy. Twenty-three metabolites were identified to be significantly altered in SCZ patients at baseline compared to healthy controls, especially arachidonic acid (AA) derived eicosanoids. These disturbances may be related to altered immunological reactions and neurotransmitter signaling. After 8-week antipsychotic treatment, there were 22 metabolites, especially AA and linoleic acid derived eicosanoids, significantly altered in posttreatment patients. Some metabolites, such as several AA derived prostaglandins, thromboxanes, and di-hydroxy-eicosatrienoic acids were reversed toward normal levels after treatment. Based on univariate analysis and orthogonal partial least-squares discriminant analysis, anandamide, oleoylethanolamine, and AA were selected as a panel of potential biomarkers for differentiating baseline SCZ patients from controls, which showed a high sensitivity (0.907), good specificity (0.843) and excellent area under the receiver operating characteristic curve (0.940). This study provided a new perspective to understand the pathophysiological mechanism and identify potential biomarkers of SCZ.

Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts

Orofacial clefts (OFCs) have multifactorial etiologies. Prenatal exposure to heavy metals can induce OFCs in animal models, but evidence from studies of human subjects is scarce. We examined whether concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) in placental tissues are associated with risk for OFCs in offspring. This population-based case-control study included 103 newborns affected by OFCs with available placental tissues and 206 controls randomly selected from 509 non-malformed newborns with available placenta samples, recruited in five rural counties in northern China. Sociodemographic information was collected using a structured questionnaire in face-to-face interviews. The concentrations of Hg, Cd, Pb, and As in placental tissues were analyzed using an inductively coupled plasma-mass spectrometry in helium mode. The median concentrations of Hg (7.4 ng/g), Cd (57.1 ng/g), and Pb (96.1 ng/g) were all statistically significantly higher in OFC cases than in controls (Hg 5.5 ng/g, Cd 38.6 ng/g, and Pb 67.9 ng/g, respectively); no differences were observed between the two groups in median concentrations of As. Concentrations above the median for all subjects were associated with a 2.33-fold (95% confidence interval [CI] 1.33-2.09) increased OFC risk for Cd and a 3.08-fold (95% CI 1.74-5.47) increased risk for Pb. The risk for OFCs increased with concentration tertiles, with an adjusted odds ratio of 3.06 (95% CI 1.36-6.88) for the second tertile and 8.18 (95% CI 6.64-18.37) for the highest tertile of Cd, and 3.88 (95% CI 1.78-8.42) for the second tertile and 5.17 (95% CI 2.37-11.29) for the highest tertile of Pb. The association between Hg concentration and OFC risk was borderline nonsignificant after adjusting for confounding factors. Prenatal exposure to Cd and Pb, as reflected by their concentrations in placental tissues, is associated with an increased risk for neonatal OFCs.

Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study

Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography–tandem mass spectrometry (LC–MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, l-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia.