Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Cytomegalovirus infection and IQ in patients with severe mental illness and healthy individuals

Cytomegalovirus (CMV) infection in immunocompetent adults is usually asymptomatic, but results in lifelong latency. Infection occurring congenitally or in immunodeficiency can lead to cognitive impairment. We aimed to investigate the associations between CMV exposure and intelligence quotient (IQ) in patients with schizophrenia spectrum disorders (SZS), bipolar spectrum disorders (BDS) and healthy controls (HC). CMV immunoglobulin G antibody concentrations were measured by immunoassay and expressed as dichotomous measures (seropositive/CMV+ vs. seronegative/CMV-). Based on a significant CMV-by-diagnosis-by-sex interaction on IQ, we investigated main and interaction effects of CMV and sex on IQ in each diagnostic category. Significant CMV-by-sex interactions were found in patient groups. In SZS, CMV+ female patients (n = 50) had significantly lower IQ than CMV- female patients (n = 33), whereas CMV+ (n = 48) and CMV- (n = 45) male patients did not differ in IQ. In BDS, CMV+ (n = 49) and CMV- (n = 37) female patients did not differ in IQ, whereas CMV+ male patients (n = 33) had significantly higher IQ than CMV- male patients (n = 32). Among HC, CMV+ (n = 138) and CMV- (n = 118) male participants as well as CMV+ (n = 125) and CMV- (n = 93) female participants did not differ in IQ. Our findings suggest that CMV exposure may affect IQ in patients with severe mental illness but not HC. © 2021 The Author

X-ray study of a test quadrant of the SODART telescopes using the expanded beam x-ray optics facility at the Daresbury synchrotron

OBJECTIVE: To develop a predictive model to identify individuals with an increased risk for undiagnosed diabetes, allowing for the availability of information within the health care system. RESEARCH DESIGN AND METHODS: A sample of participants from the Rotterdam Study (n = 1,016), aged 55-75 years, not known to have diabetes completed a questionnaire on diabetes-related symptoms and risk factors and underwent a glucose tolerance test. Predictive models were developed using stepwise logistic regression analyses with the absence or presence of newly diagnosed diabetes as the dependent variable and various items with a plausible connection to diabetes as the independent variables. The models were evaluated in another Dutch population-based study, the Hoorn Study (n = 2,364), in which the participants were aged 50-74 years. Performances of the predictive models were compared by using receiver-operator characteristics (ROC) curves. RESULTS: We developed three predictive models (PMs), PM1 contained information routinely collected by the general practitioner, while PM2 also contained variables obtainable by additional questions. The third predictive model, PM3, included variables that had to be obtained from a physical examination. These latter variables did not have additive predictive value, resulting in a PM3 similar to PM2. The area under the ROC curve was higher for PM2 than for PM1, but the 95% Cls overlapped (0.74 [0.70-0.78] and 0.68 [0.64-0.72], respectively). CONCLUSIONS: Using only information normally present in the files of a general practitioner, a predictive model was developed that performed similarly to one supplemented by information obtained from additional questions. The simplicity of PM1 makes it easy to implement in the current health care setting

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness