Structured computer-based training in the interpretation of neuroradiological images

Computer-based systems may be able to address a recognised need throughout the medical profession for a more structured approach to training. We describe a combined training system for neuroradiology, the MR Tutor that differs from previous approaches to computer-assisted training in radiology in that it provides case-based tuition whereby the system and user communicate in terms of a well-founded Image Description Language. The system implements a novel method of visualisation and interaction with a library of fully described cases utilising statistical models of similarity, typicality and disease categorisation of cases. We describe the rationale, knowledge representation and design of the system, and provide a formative evaluation of its usability and effectiveness

Schizophrenia and psychotic symptoms in families of two American Indian tribes

Abstract Background The risk of schizophrenia is thought to be higher in population isolates that have recently been exposed to major and accelerated cultural change, accompanied by ensuing socio-environmental stressors/triggers, than in dominant, mainstream societies. We investigated the prevalence and phenomenology of schizophrenia in 329 females and 253 males of a Southwestern American Indian tribe, and in 194 females and 137 males of a Plains American Indian tribe. These tribal groups were evaluated as part of a broader program of gene-environment investigations of alcoholism and other psychiatric disorders. Methods Semi-structured psychiatric interviews were conducted to allow diagnoses utilizing standardized psychiatric diagnostic criteria, and to limit cultural biases. Study participants were recruited from the community on the basis of membership in pedigrees, and not by convenience. After independent raters evaluated the interviews blindly, DSM-III-R diagnoses were assigned by a consensus of experts well-versed in the local cultures. Results Five of the 582 Southwestern American Indian respondents (prevalence = 8.6 per 1000), and one of the 331 interviewed Plains American Indians (prevalence = 3.02 per 1000) had a lifetime diagnosis of schizophrenia. The lifetime prevalence rates of schizophrenia within these two distinct American Indian tribal groups is consistent with lifetime expectancy rates reported for the general United States population and most isolate and homogeneous populations for which prevalence rates of schizophrenia are available. While we were unable to factor in the potential modifying effect that mortality rates of schizophrenia-suffering tribal members may have had on the overall tribal rates, the incidence of schizophrenia among the living was well within the normative range. Conclusion The occurrence of schizophrenia among members of these two tribal population groups is consistent with prevalence rates reported for population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis-stressor model with these stressors, commonly reported with these tribes. Nearly one-fifth of the respondents reported experiencing psychotic-like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia.</p

Origins of Spatial Working Memory Deficits in Schizophrenia: An Event-Related fMRI and Near-Infrared Spectroscopy Study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased ‘false memory’ errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased “false memory” errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Supplementary Material for: Characterization of a Novel Mutation in <b><i>SLC1A1 </i></b>Associated with Schizophrenia

We have recently described a hemi-deletion on chromosome 9p24.2 at the <i>SLC1A1</i> gene locus and its co-segregation with schizophrenia in an extended Palauan pedigree. This finding represents a point of convergence for several pathophysiological models of schizophrenia. The present report sought to characterize the biological consequences of this hemi-deletion. Dual luciferase assays demonstrated that the partially deleted allele (lacking exon 1 and the native promoter) can drive expression of a 5′-truncated <i>SLC1A1</i> using sequence upstream of exon 2 as a surrogate promoter. However, confocal microscopy and electrophysiological recordings demonstrate that the 5′-truncated <i>SLC1A1</i> lacks normal membrane localization and glutamate transport ability. To identify downstream consequences of the hemi-deletion, we first used a themed qRT-PCR array to compare expression of 84 GABA and glutamate genes in RNA from peripheral blood leukocytes in deletion carriers (n = 11) versus noncarriers (n = 8) as well as deletion carriers with psychosis (n = 5) versus those without (n = 3). Then, targeted RNA-Seq (TREx) was used to quantify expression of 375 genes associated with neuropsychiatric disorders in HEK293 cells subjected to either knockdown of <i>SLC1A1</i> or overexpression of full-length or 5′-truncated <i>SLC1A1</i>. Expression changes of several genes strongly implicated in schizophrenia pathophysiology were detected (e.g. <i>SLC1A2</i>,<i> SLC1A3</i>,<i> SLC1A6</i>,<i> SLC7A11</i>,<i> GRIN2A</i>,<i> GRIA1 </i>and<i> DLX1</i>)

Schizophrenia and GABAA receptor subunit genes

Alterations in ?-aminobutyric acid (GABA) neurotransmission have been indirectly implicated in the pathogenesis of schizophrenia. Using nine multiplex pedigrees, we tested for linkage between schizophrenia and simple sequence repeat polymorphisms for the GABAA receptor ?1, ?2, ?4, ?5, ?6, ?1 and ?3 subunit genes. Evidence of linkage was not found when assuming either autosomal dominant or autosomal recessive inheritance. The non-parametric sib pair test also did not reveal significant evidence of deviation from expected segregation ratios

Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate

An increased abundance of runs of homozygosity (ROH) has been associated with risk for various diseases, including schizophrenia. Here we investigate the characteristics of ROH in Palau, an Oceanic population, evaluating whether these characteristics are related to risk for psychotic disorders and the nature of this association. To accomplish these aims we evaluate a sample of 203 cases with schizophrenia and related psychotic disorders-representing almost complete ascertainment of affected individuals in the population-and contrast their ROH to that of 125 subjects chosen to function as controls. While Palauan diagnosed with psychotic disorders tend to have slightly more ROH regions than controls, the distinguishing features are that they have longer ROH regions, greater total length of ROH, and their ROH tends to co-occur more often at the same locus. The nature of the sample allows us to investigate whether rare, highly penetrant recessive variants generate such case-control differences in ROH. Neither rare, highly penetrant recessive variants nor individual common variants of large effect account for a substantial proportion of risk for psychosis in Palau. These results suggest a more nuanced model for risk is required to explain patterns of ROH for this population

Supplementary Material for: Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31

<p>To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlights <i>PCDH10</i>, encoding a cadherin-related neuronal receptor, as possibly involved in risk.</p