Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

Three-dimensional bone CT reconstruction anatomy of the vidian canal.

OBJECTIVES: To examine the anatomical features of the anterior opening of the vidian canal using three-dimensional (3D) computed tomography (CT) images of the bone. METHODS: We reviewed 62 patients who had undergone bilateral vidian neurectomies. One hundred and twenty-four vidian canals and their surrounding anatomies were analyzed. 3D images were reconstructed using algorithms and compared with conventional two-dimensional (2D) CT images. RESULTS: A bony prominence that overlaid the vidian canal along the sphenoid sinus floor was found in 60 (48.39 %) canals. Pneumatization of the pterygoid process was observed in 45 sides (36.29%). No significant discrepancy was found in detecting these variances between the 2D and the 3D images. The presence of a surgically favorable gap between the palatine and the sphenoid bone was seen in 25 sides (20.16%) without significant association with pterygoid process pneumatization or vidian canal protrusion. This gap was not identified on the 2D CT scans. CONCLUSION: 3D CT reconstruction images of bone provide superior delineation of the gap between the palatine and the sphenoid bone, which is a critical variation for vidian neurectomy. This useful method may contribute to better prediction and guidance of the surgical approach to the vidian canal and pterygopalatine fossa.

A genome-wide quantitative trait loci scan of neurocognitive performances in families with schizophrenia.

Patients with schizophrenia frequently display neurocognitive dysfunction, and genetic studies suggest it to be an endophenotype for schizophrenia. Genetic studies of such traits may thus help elucidate the biological pathways underlying genetic susceptibility to schizophrenia. This study aimed to identify loci influencing neurocognitive performance in schizophrenia. The sample comprised of 1207 affected individuals and 1035 unaffected individuals of Han Chinese ethnicity from 557 sib-pair families co-affected with DSM-IV (Diagnostic and Statistical Manual, Fourth Edition) schizophrenia. Subjects completed a face-to-face semi-structured interview, the continuous performance test (CPT) and the Wisconsin card sorting test (WCST), and were genotyped with 386 microsatellite markers across the genome. A series of autosomal genome-wide multipoint nonparametric quantitative trait loci (QTL) linkage analysis were performed in affected individuals only. Determination of genome-wide empirical significance was performed using 1000 simulated genome scans. One linkage peak attaining genome-wide significance was identified: 12q24.32 for undegraded CPT hit rate [nonparametric linkage z (NPL-Z) scores = 3.32, genome-wide empirical P = 0.03]. This result was higher than the peak linkage signal obtained in the previous genome-wide scan using a dichotomous diagnosis of schizophrenia. The identification of 12q24.32 as a QTL has not been consistently implicated in previous linkage studies on schizophrenia, which suggests that the analysis of endophenotypes provides additional information from what is seen in analyses that rely on diagnoses. This region with linkage to a particular neurocognitive feature may inform functional hypotheses for further genetic studies for schizophrenia.

Clustering by neurocognition for fine mapping of the schizophrenia susceptibility loci on chromosome 6p.

Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for eight neurocognitive test variables of the continuous performance test (CPT) and the Wisconsin card sorting test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms (SNPs) covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of nondeficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or nondeficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia.

Relative reliability of the auditory evoked potential and Bispectral Index for monitoring sedation level in surgical intensive care patients.

Sedation is an important adjunct therapy for patients in the intensive care unit. The objective of the present study was to observe correlation between an established subjective measure, the Ramsay Sedation Scale, and two objective tools for monitoring critically ill patients: the Bispectral Index (BIS) and auditory evoked potential. Ninety patients undergoing major surgery scheduled for postoperative mechanical ventilation and continuous sedation with propofol and fentanyl were selected. Electrodes for determining BIS and auditory evoked potential were placed on the foreheads of all patients according to manufacturer's specifications at least six hours after patients' arrival at the intensive care unit. Ramsay Sedation Scale, BIS, signal quality index, composite A-line autoregressive index (AAI) and electromyographic activities were recorded every five minutes for 30 minutes. BIS and AAI showed good correlation amongst readings (r(s)=0.697, P <0.01). Both were significantly influenced by electromyographic activities (BIS, r(s)=0.735, P <0.01; AAI, r(s)=0.856, P <0.01). Comparison of BIS and AAI revealed an acceptable correlation between electroencephalogram variables and the Ramsay Sedation Scale (BIS, tau=-0.689; AAI, tau=-0.621; P <0.01). In conclusion, the auditory evoked potential and BIS monitors revealed an acceptable correlation with the Ramsay Sedation Scale. However, the BIS and auditory evoked potential monitors do not perform adequately as a substitute in the assessment of sedated intensive care unit patients. These monitors could be used as part of an integrated approach for the evaluation of those patients especially when the subjective scales do not work well in the setting of neuromuscular blockade or may not be sufficiently sensitive to evaluate very deep sedation.

Extractability and fractionation of heavy metals in chemically treated sewage sludges.

Four chemically treated sludges, lime-treated (LS), lime/sodium silicate-treated (LSS), cement-treated (CS), and cement/sodium silicate-treated (CSS) were produced form the chemical treatment of aerobic digested sewage sludge cake, using lime, cement, and sodium silicate as additives. Ex tractability and fractionation of the heavy metals (Cu, Pb, Cr, and Zn) in these products and untreated sludge (S) were investigated using sequential extraction, single extraction, and 13C cross-polarization magic angle spinning nuclear magnetic resonance analysis (13C-NMR). These approaches revealed that chemical treatment of sewage sludge makes sludge Cu, Pb, and Cr more extractable. It was attributed to the irreversible dissolution of a portion of organics at very high pH during chemical treatment of sludge. The enhanced extraction of some metals having higher affinity to organics, e.g. Cu and Pb, from the chemically treated sludges was due to their complexion with the above soluble organics.