Reading skills in mental illness: A multimodal analysis

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London.Reading is a complex process involving multiple skills – i.e., phonological processing, comprehension, and word recognition. It is also a significant predictor of socio-economic status, academic achievement, and has vast importance in everyday functioning. Reading deficits can lead to maladaptive behaviour and consequently increase the risk of incarceration. Severe reading skills deficits are present in schizophrenia, and to some extent in people with psychopathy and forensic populations (Chapter 2 – systematic review and meta-analysis). Considering the overlap between discreet clinical diagnoses and the presence of symptoms and psychopathology-related traits in non-clinical populations, this thesis aimed to examine the behavioural and neurofunctional associations between reading skills and dimensional psychopathology-related traits in the general and clinical populations. To address these aims, three empirical investigations were carried out: i) behavioural studies (Chapters 4 and 5) investigating the relationship between reading-related skills, as indexed by performance on a lexical decision task (LDT) requiring word-nonword recognition, and a range of psychopathologyrelated traits (schizotypy, psychopathy, impulsivity, and affective traits) in a general population sample (N = 78), ii) a functional magnetic resonance imaging (fMRI) study (Chapter 6) investigating the neural correlates of this relationship (N = 22), and iii) a preliminary clinical study (Chapter 7) investigating the relationship between reading skills of phonological processing and comprehension, dimensional psychopathology, and cognition (verbal learning and memory, IQ, and executive functioning) in a forensic psychiatric sample (N = 15). The findings suggest that traits of positive schizotypy (Unusual Experiences), fearless dominance (Meanness) and callous aggression (Boldness) in psychopathy, and motor impulsivity can modulate behavioural responses in word-nonword recognition (LDT performance) in the general population. Higher motor impulsivity was the trait most strongly associated with lower LDT performance accuracy in non-native speakers. At the neural level also, motor impulsivity was most consistently associated with lower activity in some of the brain areas that are crucial for word recognition, namely the fusiform and inferior frontal gyri (IFG). In the forensic psychiatric sample, 13/15 patients were diagnosed with a psychotic disorder and all reading skills were significantly below their age norms and showed some association with executive function and verbal learning. In this sample, Lifestyle psychopathy was significantly associated with poor LDT performance, especially in low-frequency words recognition and Cognitive Perceptual aspect of positive schizotypy with severe deficits in reading comprehension, overall reading ability, and poor low-frequency word recognition. In conclusion, positive schizotypy and psychosis seem to be associated with poor reading skills. Higher psychopathy and motor impulsivity traits seem to predict of poor reading skills across the general and clinical populations and modulate neural activity during correct word-nonword recognition. These findings provide insight into the relationship between dimensional psychopathology-related traits, their comorbidities, and reading skills in clinical and non-clinical populations, and suggest that poor reading skills in clinical populations should be considered as important treatment targets

The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial

Abstract Background Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. Methods In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. Discussion The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Trial registration Current Controlled Trials ISRCTN, ID: 15742788. Registered on 12 June 2017

Additional file 1: of The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial

SPIRIT Checklist. Recommended items to address in a clinical trial protocol and related documents. (DOC 120 kb

British Society for the Psychology of Individual Differences 2021 Conference

This is the host page for the content from the BSPID 2021 conference. On this page are the presentations and posters from our event on 17th June 202

Sequential development of several RT-qPCR tests using LNA nucleotides and dual probe technology to differentiate SARS-CoV-2 from influenza A and B

Sensitive and accurate RT-qPCR tests are the primary diagnostic tools to identify SARS-CoV-2-infected patients. While many SARS-CoV-2 RT-qPCR tests are available, there are significant differences in test sensitivity, workflow (e.g. hands-on-time), gene targets and other functionalities that users must consider. Several publicly available protocols shared by reference labs and public health authorities provide useful tools for SARS-CoV-2 diagnosis, but many have shortcomings related to sensitivity and laborious workflows. Here, we describe a series of SARS-CoV-2 RT-qPCR tests that are originally based on the protocol targeting regions of the RNA-dependent RNA polymerase (RdRp) and envelope (E) coding genes developed by the Charite Berlin. We redesigned the primers/probes, utilized locked nucleic acid nucleotides, incorporated dual probe technology and conducted extensive optimizations of reaction conditions to enhance the sensitivity and specificity of these tests. By incorporating an RNase P internal control and developing multiplexed assays for distinguishing SARS-CoV-2 and influenza A and B, we streamlined the workflow to provide quicker results and reduced consumable costs. Some of these tests use modified enzymes enabling the formulation of a room temperature-stable master mix and lyophilized positive control, thus increasing the functionality of the test and eliminating cold chain shipping and storage. Moreover, a rapid, RNA extraction-free version enables high sensitivity detection of SARS-CoV-2 in about an hour using minimally invasive, self-collected gargle samples. These RT-qPCR assays can easily be implemented in any diagnostic laboratory and can provide a powerful tool to detect SARS-CoV-2 and the most common seasonal influenzas during the vaccination phase of the pandemic

Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH in mtDNA-deficient cells is fully activated with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by introduction of an alternative oxidase. Further, deletion of DHODH interferes with tumor formation in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little effect. Our results show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents.status: publishe