Cognitive bias modification for paranoia (CBM-pa): a randomised controlled feasibility study in patients with distressing paranoid beliefs.

BACKGROUND: Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose-response and (iv) select primary outcomes for future trials. METHODS: In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment. RESULTS: A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30-40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = -0.48 to -0.76), improved symptoms of paranoia (d = -0.19 to -0.38), and lower depressed and anxious mood (d = -0.03 to -0.29). The intervention effect was evident after the third session. CONCLUSIONS: CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

Psychological flexibility, distress, and quality of life in secondary progressive multiple sclerosis: A cross-sectional study.

INTRODUCTION: One of the strongest predictors of successful coping in multiple sclerosis (MS) is the extent to which one can accept the diagnosis and limitations associated with the disease. Acceptance is also one of three core processes of psychological flexibility - a malleable treatment target of some psychological therapies. This is the ability to notice and accept the presence of thoughts and feelings without being swept along by them, engaging in the present moment, and making decisions in line with personal values. Poor psychological flexibility is associated with elevated levels of distress in the general population. However, we do not know the level of psychological flexibility in people with MS, or its relationship to distress or quality of life when the disease becomes more physically disabling. The aims of this study were to determine the level of psychological flexibility, and its relationship with distress and quality of life in secondary progressive multiple sclerosis (SPMS), a subtype of MS with increased severity of disability and distress. METHOD: This cross-sectional analytic study used data collected by the UK MS Register. Pre-existing data on distress, quality of life, disability, and demographics collected by the UK MS Register were combined with a psychological flexibility measure and its component parts, collected for the purpose of this study. Patient demographics and questionnaire data were recorded for distress, quality of life, and psychological flexibility. Pearson's correlations were used to examine bivariate relationships between distress, quality of life, disability and psychological flexibility. Whether psychological flexibility moderated the relationship between disability (predictor), distress and quality of life (outcomes) was also investigated. RESULTS: Between February and March 2020, 628 participants with SPMS completed the CompACT and had a recent (<12 months) HADS questionnaire (Mage = 60.66, 70.90% women). On the HADS questionnaire subscales, 44% of the sample scored above the MS clinical cut-off (≥8) for anxiety (M = 7.09, SD = 4.57), and 30% above the clinical cut off (≥11) for depression (M = 8.35, SD = 4.21). Psychological flexibility (M = 81.94, SD = 22.60) and its components were each moderately negatively correlated with total distress (r = -0.65), anxiety (r = -0.58), and depression (r = -0.56). A second subsample (n = 434) completed the EQ-5D-5L health-related quality of life measure, which was moderately positively correlated with psychological flexibility (r = 0.47). A third subsample (n = 210) found a weak negative relationship between psychological flexibility and disability (r = -0.16), a weak positive relationship between distress and disability (r = 0.26), and a moderate negative relationship between quality of life and disability (r = -0.56). Psychological flexibility was not found to moderate the relationships between disability and anxiety, depression, or quality of life in SPMS. DISCUSSION: Greater psychological flexibility was associated with lower self-reported distress and higher quality of life in this SPMS sample. It was not shown to moderate the extent to which physical disability predicts distress or quality of life in SPMS. These findings demonstrate that greater psychological flexibility is related to better coping outcomes (lower distress, higher quality of life) in SPMS. If psychological flexibility can be increased in people with SPMS, this could lead to a reduction in distress and improvement in quality of life, although directionality could not be attributed with these methods. Further longitudinal evidence and trials of psychological flexibility-focussed interventions are needed.

Experiences of adjustment to secondary progressive multiple sclerosis: a meta-ethnographic systematic review.

PURPOSE: To provide an overview of the experiences and needs of patients adjusting to life after receiving a diagnosis of secondary progressive multiple sclerosis (SPMS). METHOD: We conducted a meta-ethnographic synthesis of qualitative studies on the experiences of transition to SPMS, based on a systematic literature search of CINAHL, PsycINFO, Embase, MEDLINE, and Web of Science. Identified studies were quality-appraised using a critical appraisal checklist, and individual findings synthesised inductively. RESULTS: The synthesis included 12 articles with 144 people with SPMS. Adjusting to SPMS transition encompassed a variety of reactions and coping strategies. Successful adjustment was associated with accepting and adapting coping strategies, and availability of social support and relationships. Clinical services increased uncertainty around adjustment where patients felt clinicians were not transparent with them about their changing diagnosis. CONCLUSIONS: People adjust to SPMS in different ways, with the success of adjustment influenced by a patient's primary coping mechanism. Coping mechanisms are determined by pre-existing individual differences, alongside engagement with, and quality of, social support networks and activities. Services should ensure that people are provided with informational support about their illness progression, and emotional support concerning coping strategies, social networks, and physical activity, as these are key determinants of successful adjustment.IMPLICATIONS FOR REHABILITATIONAdjusting to secondary progressive multiple sclerosis is a difficult and stressful time for patients.Coping strategies patients use, their support network and their activity levels are key determinants of successful adjustment.Clinicians should be open with patients about their assessment of their changing diagnosis, rather than trying to avoid upsetting the patient by withholding information.Clinical services should be proactive in supporting patients during adjustment with learning positive coping strategies, and maintaining or increasing social relationships and activity levels.

Cognitive Bias Modification for paranoia (CBM-pa): study protocol for a randomised controlled trial.

BACKGROUND: Persecutory delusions are the most common type of delusions in psychosis and present in around 10-15% of the general population. Persecutory delusions are thought to be sustained by biased cognitive and emotional processes. Recent advances favour targeted interventions, focussing on specific symptoms or mechanisms. Our aim is to test the clinical feasibility of a novel psychological intervention, which manipulates biased interpretations toward more adaptive processing, in order to reduce paranoia in patients. METHODS: The 'Cognitive Bias Modification for paranoia' (CBM-pa) study is a feasibility, double-blind, randomised controlled trial (RCT) for 60 stabilised outpatients with persistent, distressing paranoid symptoms. Patients will be randomised at a 50:50 ratio, to computerised CBM-pa or a text-reading control intervention, receiving one 40-min session per week, for 6 weeks. CBM-pa involves participants reading stories on a computer screen, completing missing words and answering questions about each story in a way that encourages more helpful beliefs about themselves and others. Treatment as Usual will continue for patients in both groups. Patients will be assessed by a researcher blind to allocation, at baseline, each interim session, post treatment and 1- and 3-month follow-up post treatment. The primary outcome is the feasibility parameters (trial design, recruitment rate and acceptability) of the intervention. The secondary outcomes are clinical symptoms (including severity of paranoia) as assessed by a clinical psychologist, and 'on-line' measurement of interpretation bias and stress/distress. The trial is funded by the NHS National Institute for Health Research. DISCUSSION: This pilot study will test whether CBM-pa has the potential to be a cost-effective, accessible and flexible treatment. If the trial proves feasible and demonstrates preliminary evidence of efficacy, a fully powered RCT will be warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 90749868 . Retrospectively registered on 12 May 2016.

Conditional random fields for fast, large-scale genome-wide association studies.

Understanding the role of genetic variation in human diseases remains an important problem to be solved in genomics. An important component of such variation consist of variations at single sites in DNA, or single nucleotide polymorphisms (SNPs). Typically, the problem of associating particular SNPs to phenotypes has been confounded by hidden factors such as the presence of population structure, family structure or cryptic relatedness in the sample of individuals being analyzed. Such confounding factors lead to a large number of spurious associations and missed associations. Various statistical methods have been proposed to account for such confounding factors such as linear mixed-effect models (LMMs) or methods that adjust data based on a principal components analysis (PCA), but these methods either suffer from low power or cease to be tractable for larger numbers of individuals in the sample. Here we present a statistical model for conducting genome-wide association studies (GWAS) that accounts for such confounding factors. Our method scales in runtime quadratic in the number of individuals being studied with only a modest loss in statistical power as compared to LMM-based and PCA-based methods when testing on synthetic data that was generated from a generalized LMM. Applying our method to both real and synthetic human genotype/phenotype data, we demonstrate the ability of our model to correct for confounding factors while requiring significantly less runtime relative to LMMs. We have implemented methods for fitting these models, which are available at http://www.microsoft.com/science.

Estimating genome-wide IBD sharing from SNP data via an efficient hidden Markov model of LD with application to gene mapping.

MOTIVATION: Association analysis is the method of choice for studying complex multifactorial diseases. The premise of this method is that affected persons contain some common genomic regions with similar SNP alleles and such areas will be found in this analysis. An important disadvantage of GWA studies is that it does not distinguish between genomic areas that are inherited from a common ancestor [identical by descent (IBD)] and areas that are identical merely by state [identical by state (IBS)]. Clearly, areas that can be marked with higher probability as IBD and have the same correlation with the disease status of identical areas that are more probably only IBS, are better candidates to be causative, and yet this distinction is not encoded in standard association analysis. RESULTS: We develop a factorial hidden Markov model-based algorithm for computing genome-wide IBD sharing. The algorithm accepts as input SNP data of measured individuals and estimates the probability of IBD at each locus for every pair of individuals. For two g-degree relatives, when g > or = 8, the computation yields a precision of IBD tagging of over 50% higher than previous methods for 95% recall. Our algorithm uses a first-order Markovian model for the linkage disequilibrium process and employs a reduction of the state space of the inheritance vector from being exponential in g to quadratic. The higher accuracy along with the reduced time complexity marks our method as a feasible means for IBD mapping in practical scenarios. AVAILABILITY: A software implementation, called IBDMAP, is freely available at http://bioinfo.cs.technion.ac.il/IBDmap.

Speeding up HMM algorithms for genetic linkage analysis via chain reductions of the state space.

UNLABELLED: We develop an hidden Markov model (HMM)-based algorithm for computing exact parametric and non-parametric linkage scores in larger pedigrees than was possible before. The algorithm is applicable whenever there are chains of persons in the pedigree with no genetic measurements and with unknown affection status. The algorithm is based on shrinking the state space of the HMM considerably using such chains. In a two g-degree cousins pedigree the reduction drops the state space from being exponential in g to being linear in g. For a Finnish family in which two affected children suffer from a rare cold-inducing sweating syndrome, we were able to reduce the state space by more than five orders of magnitude from 2(50) to 2(32). In another pedigree of state-space size of 2(27), used for a study of pituitary adenoma, the state space reduced by a factor of 8.5 and consequently exact linkage scores can now be computed, rather than approximated. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.