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.

Automatic Detection of Cognitive Impairment with Virtual Reality.

Cognitive impairment features in neuropsychiatric conditions and when undiagnosed can have a severe impact on the affected individual's safety and ability to perform daily tasks. Virtual Reality (VR) systems are increasingly being explored for the recognition, diagnosis and treatment of cognitive impairment. In this paper, we describe novel VR-derived measures of cognitive performance and show their correspondence with clinically-validated cognitive performance measures. We use an immersive VR environment called VStore where participants complete a simulated supermarket shopping task. People with psychosis (k=26) and non-patient controls (k=128) participated in the study, spanning ages 20-79 years. The individuals were split into two cohorts, a homogeneous non-patient cohort (k=99 non-patient participants) and a heterogeneous cohort (k=26 patients, k=29 non-patient participants). Participants' spatio-temporal behaviour in VStore is used to extract four features, namely, route optimality score, proportional distance score, execution error score, and hesitation score using the Traveling Salesman Problem and explore-exploit decision mathematics. These extracted features are mapped to seven validated cognitive performance scores, via linear regression models. The most statistically important feature is found to be the hesitation score. When combined with the remaining extracted features, the multiple linear regression model resulted in statistically significant results with R2 = 0.369, F-Stat = 7.158, p(F-Stat) = 0.000128.

An evaluation of the variation and underuse of clozapine in the United Kingdom.

BACKGROUND: Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. METHODS: We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. FINDINGS: There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. INTERPRETATION: There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.

The role of expecting feedback during decision-making under risk.

Sometimes choice is followed by outcome feedback and other times it is not. It remains unknown whether humans prefer gambling when they expect feedback to be revealed. Regarding this question, decision-making theories make alternative predictions. Some theories have proposed that choice is influenced by whether one expects to be disappointed in the future. Given that feedback is sometimes disappointing, these theories predict increased aversion towards gambling when feedback is expected compared to when feedback is not expected. The opposite effect is predicted by theories of curiosity, which postulate reduction of uncertainty as an important behavioural drive. Given that feedback reduces uncertainty, these theories predict that gambling will be favoured when feedback is expected. To examine whether expecting feedback influences gambling behaviour, we recorded functional neuroimaging data while participants performed a novel decision-making task requiring to chose between a sure option and a gamble. Crucially, participants expected to receive feedback in some trials but not in other trials. Consistent with theories of curiosity, we found that expecting feedback increased gambling propensity. At the neural level, at option presentation the increased value of gambling during feedback was reflected in activity in the ventral striatum. This suggests that, together with its established role in signalling reward, the ventral striatum also processes a form of epistemic value. Our study demonstrates that gambling becomes more attractive when feedback is expected and suggests that striatal activity could signal the value of feedback information.

Integrated care in mental health: next steps after the NHS Long Term Plan.

Health and social care face growing and conflicting pressures: mounting complex needs of an ageing population, restricted funding and a workforce recruitment and retention crisis. In response, in the UK the NHS Long Term Plan promises increased investment and an emphasis on better 'integrated' care. We describe key aspects of integration that need addressing.Declaration of interestD.K.T. and S.S.S. are on the editorial board of the British Journal of Psychiatry and executives of the Academic Faculty at the Royal College of Psychiatrists. A.J.B.J., H.P. and Z.M. have roles at the Royal College of Psychiatrists that include evaluation of integrated care systems. A.J.B.J. is married to Dr Sarah Wollaston, Member of Parliament for Totnes and Chair of the Health Select Committee.

Correction to: A systematic review of the effects of low-frequency repetitive transcranial magnetic stimulation on cognition.

The original version of this article unfortunately contained a mistake. The author would like to include the below acknowledgement section.

Correction to: Skating on thin ice: pragmatic prescribing for medication refractory schizophrenia.

After publication of the original article [1], the authors have notified us that there was an oversight on acknowledging funding received for the study. They would like to mention that Professor Sukhi Shergill was funded by an ERC Consolidator Award.

Visual Population Receptive Fields in People with Schizophrenia Have Reduced Inhibitory Surrounds.

People with schizophrenia (SZ) experience abnormal visual perception on a range of visual tasks, which have been linked to abnormal synaptic transmission and an imbalance between cortical excitation and inhibition. However, differences in the underlying architecture of visual cortex neurons, which might explain these visual anomalies, have yet to be reported in vivo Here, we probed the neural basis of these deficits using fMRI and population receptive field (pRF) mapping to infer properties of visually responsive neurons in people with SZ. We employed a difference-of-Gaussian model to capture the center-surround configuration of the pRF, providing critical information about the spatial scale of the pRFs inhibitory surround. Our analysis reveals that SZ is associated with reduced pRF size in early retinotopic visual cortex, as well as a reduction in size and depth of the inhibitory surround in V1, V2, and V4. We consider how reduced inhibition might explain the diverse range of visual deficits reported in SZ.SIGNIFICANCE STATEMENT People with schizophrenia (SZ) experience abnormal perception on a range of visual tasks, which has been linked to abnormal synaptic transmission and an imbalance between cortical excitation/inhibition. However, associated differences in the functional architecture of visual cortex neurons have yet to be reported in vivo We used fMRI and population receptive field (pRF) mapping to demonstrate that the fine-grained functional architecture of visual cortex in people with SZ differs from unaffected controls. SZ is associated with reduced pRF size in early retinotopic visual cortex largely due to reduced inhibitory surrounds. An imbalance between cortical excitation and inhibition could drive such a change in the center-surround pRF configuration and ultimately explain the range of visual deficits experienced in SZ.

Realising stratified psychiatry using multidimensional signatures and trajectories.

BACKGROUND: Stratified or personalised medicine targets treatments for groups of individuals with a disorder based on individual heterogeneity and shared factors that influence the likelihood of response. Psychiatry has traditionally defined diagnoses by constellations of co-occurring signs and symptoms that are assigned a categorical label (e.g. schizophrenia). Trial methodology in psychiatry has evaluated interventions targeted at these categorical entities, with diagnoses being equated to disorders. Recent insights into both the nosology and neurobiology of psychiatric disorder reveal that traditional categorical diagnoses cannot be equated with disorders. We argue that current quantitative methodology (1) inherits these categorical assumptions, (2) allows only for the discovery of average treatment response, (3) relies on composite outcome measures and (4) sacrifices valuable predictive information for stratified and personalised treatment in psychiatry. METHODS AND FINDINGS: To achieve a truly 'stratified psychiatry' we propose and then operationalise two necessary steps: first, a formal multi-dimensional representation of disorder definition and clinical state, and second, the similar redefinition of outcomes as multidimensional constructs that can expose within- and between-patient differences in response. We use the categorical diagnosis of schizophrenia-conceptualised as a label for heterogeneous disorders-as a means of introducing operational definitions of stratified psychiatry using principles from multivariate analysis. We demonstrate this framework by application to the Clinical Antipsychotic Trials of Intervention Effectiveness dataset, showing heterogeneity in both patient clinical states and their trajectories after treatment that are lost in the traditional categorical approach with composite outcomes. We then systematically review a decade of registered clinical trials for cognitive deficits in schizophrenia highlighting existing assumptions of categorical diagnoses and aggregate outcomes while identifying a small number of trials that could be reanalysed using our proposal. CONCLUSION: We describe quantitative methods for the development of a multi-dimensional model of clinical state, disorders and trajectories which practically realises stratified psychiatry. We highlight the potential for recovering existing trial data, the implications for stratified psychiatry in trial design and clinical treatment and finally, describe different kinds of probabilistic reasoning tools necessary to implement stratification.

White matter deficits in schizophrenia are global and don't progress with age.

INTRODUCTION: Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be. The distribution and timing of differences may help explain their origin; however, results are usually dependent on the analytical method. We therefore sought to examine the extent of differences and their relationship with age using two different methods. METHODS: A combined voxel-based whole-brain study and a tract-based spatial-statistics study of 104 patients with schizophrenia and 200 matched healthy controls, aged between 17 and 63 years. RESULTS: Fractional anisotropy was reduced throughout the brain in both analyses. The relationship of fractional anisotropy with age differed between patients and controls, with controls showing the gentle fractional anisotropy decline widely noted but patients showing an essentially flat relationship: younger patients had lower fractional anisotropy than controls, but the difference disappeared with age. Mean diffusivity was widely increased in patients. CONCLUSION: Reduction in fractional anisotropy and increase in mean diffusivity would be consistent with global disruption in myelination; the relationship with age would suggest this is present already at the onset of their illness, but does not progress.