Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis:An ENIGMA Working Group Mega-analysis

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen.Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.Peer reviewe

An overview of eye problems in Singapore's elderly.

Singapore Medical Journal324268-27

Assessment of surface water quality in the Malaysian Coastal Waters by using multivariate analyses

Coastal water samples were collected from 20 sampling sites in the southern part of Peninsular Malaysia. Seven physico-chemical parameters were measured directly in-situ while water samples were collected and analysed for 6 dissolved trace metal concentrations. The surface water (0-20 cm) physico-chemical parameters including temperature, salinity, dissolved oxygen (DO), pH, total dissolved solids (TDS), specific conductance (SpC) and turbidity while the dissolved trace metals were Cd, Cu, Fe, Ni, Pb and Zn. The ranges for the physico-chemical parameters were 28.07-35.6ºC for temperature, 0.18-32.42 ppt for salinity, 2.20-12.03 mg/L for DO, 5.50-8.53 for pH, 0.24-31.65 mg/L for TDS, 368-49452 μS/cm for SpC and 0-262 NTU for turbidity while the dissolved metals (mg/L) were 0.013-0.147 for Cd, 0.024-0.143 for Cu, 0.266-2.873 for Fe, 0.027-0.651 for Ni, 0.018-0.377 for Pb and 0.032-0.099 for Zn. Based on multivariate analysis (including correlation, cluster and principal component analyses), the polluted sites were found at Kg. Pasir Puteh and Tg. Kupang while Ni and Pb were identified as two major dissolved metals of high variation in the coastal waters. Therefore, water quality monitoring and control of release of untreated anthropogenic wastes into rivers and coastal waters are strongly needed

Interpretation of undrained shear strength observed in confined triaxial compression tests on compacted clay

This paper presents an interpretation technique to quantify the effects of compaction state and matric suction on the undrained shear strength of compacted clay under confined undrained triaxial compression. This novel technique is based on the mathematical frameworks of SHANSEP (Stress History and Normalized Soil Engineering Property) method for saturated soil and BBM (Barcelona Basic model) for unsaturated soil. Test data of compacted Calgary till were analyzed and interpreted using the proposed technique. The interpretation technique is very useful in delineating the relative impacts of the factors on the behavioral trends in measured undrained shear strength. It was found that in addition to the initial compacted void ratio and suction, soil structure and failure mode exert significant influence on the undrained shear strength of compacted clay. This technique is attractive to engineering practitioners because the confined undrained compression tests (with no pore air and water pressure measurement) are much simpler and less time consuming compared to rigorous laboratory tests on unsaturated soil.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Magnetic Resonance Imaging of Cruciate Ligament Injuries of the Knee

AbstractThe anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are important stabilizers of the knee. These ligaments are commonly injured in sports and motor vehicle accidents. An accurate diagnosis of cruciate ligament injuries is vital in patient care. Magnetic resonance imaging (MRI) can diagnose cruciate ligament injuries with high accuracy. The imaging diagnosis should be based on primary signs, although the secondary signs are sometimes useful, particularly in chronic cases. The detection of associated injuries of other structures of the knee, including menisci, collateral ligaments, cartilage, and bone, are also important. Accurate interpretation of the MRI examination requires a meticulous MRI technique, knowledge of the imaging anatomy, and understanding of the lesion appearance. This pictorial essay reviews the MRI appearance of normal and injured cruciate ligaments. Mechanisms of injury, primary and secondary MRI signs, and associated abnormalities are discussed

Effect of Fiber Orientation on Mechanical Properties of Kenaf-Reinforced Polymer Composite

The increase of environmental awareness has led to interest in the use of materials with eco-friendly attributes. In this study, a sandwich composite was developed from polyester and kenaf fiber with various orientation arrangements. Polyester/kenaf sandwich composite was fabricated through the combination of a hand lay-up process and cold compression. The tensile, flexural, and Izod impact tests of the sandwich composites were evaluated by using a universal tensile tester and an impact tester. The thermal stability of polyester/kenaf sandwich composite and plywood were investigated by using a thermogravimetric analyser. Results showed that the polyester/kenaf sandwich composite with kenaf fiber in anisotropy orientation achieved the highest mechanical properties. The kenaf fiber in anisotropic orientation could absorb the impact energy and allow the sandwich composite to withstand greater impact forces compared to composite with fiber in perpendicular or isotropic orientations. The polyester/kenaf sandwich composite also showed higher thermal stability compared to a conventional plywood sheet. Thus, the fabrication of polyester/kenaf sandwich composite with kenaf fiber in an anisotropic orientation design has great potential to replace plywood sheets for beam construction applications