Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode

Abstract Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16–65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood

The ARIA trial protocol: a randomised controlled trial to assess the clinical, technical, and cost-effectiveness of a cloud-based, ARtificially Intelligent image fusion system in comparison to standard treatment to guide endovascular Aortic aneurysm repair

BackgroundEndovascular repair of aortic aneurysmal disease is established due to perceived advantages in patient survival, reduced postoperative complications, and shorter hospital lengths of stay. High spatial and contrast resolution 3D CT angiography images are used to plan the procedures and inform device selection and manufacture, but in standard care, the surgery is performed using image-guidance from 2D X-ray fluoroscopy with injection of nephrotoxic contrast material to visualise the blood vessels. This study aims to assess the benefit to patients, practitioners, and the health service of a novel image fusion medical device (Cydar EV), which allows this high-resolution 3D information to be available to operators at the time of surgery.MethodsThe trial is a multi-centre, open label, two-armed randomised controlled clinical trial of 340 patient, randomised 1:1 to either standard treatment in endovascular aneurysm repair or treatment using Cydar EV, a CE-marked medical device comprising of cloud computing, augmented intelligence, and computer vision. The primary outcome is procedural time, with secondary outcomes of procedural efficiency, technical effectiveness, patient outcomes, and cost-effectiveness. Patients with a clinical diagnosis of AAA or TAAA suitable for endovascular repair and able to provide written informed consent will be invited to participate.DiscussionThis trial is the first randomised controlled trial evaluating advanced image fusion technology in endovascular aortic surgery and is well placed to evaluate the effect of this technology on patient outcomes and cost to the NHS.Trial registrationISRCTN13832085. Dec. 3, 202

Psychological and demographic characteristics of 368 patients with dissociative seizures: data from the CODES cohort

Background We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology. Methods Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic). Results Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men. Conclusions Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort

Cognitive–behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT

BACKGROUND: Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive-behavioural therapy for adults with dissociative seizures. DESIGN: This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. SETTING: This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive-behavioural therapy services. PARTICIPANTS: Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. INTERVENTIONS: Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive-behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. MAIN OUTCOME MEASURES: The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. RESULTS: In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive-behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1-35 dissociative seizures); cognitive-behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0-20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive-behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7-12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect -0.39, 95% confidence interval -0.61 to -0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive-behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval -0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive-behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. LIMITATIONS: Unlike outcome assessors, participants and clinicians were not blinded to the interventions. CONCLUSIONS: There was no significant additional benefit of dissociative seizure-specific cognitive-behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive-behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive-behavioural therapy. FUTURE WORK: Examination of moderators and mediators of outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information

Evaluation of intensive community care services for young people with psychiatric emergencies: study protocol for a multi-centre parallel-group, single-blinded randomized controlled trial with an internal pilot phase

Background: Over 3000 young people under the age of 18 are admitted to Tier 4 Child and Adolescent Mental Health Services (CAMHS) inpatient units across the UK each year. The average length of hospital stay for young people across all psychiatric units in the UK is 120 days. Research is needed to identify the most effective and efficient ways to care for young people (YP) with psychiatric emergencies. This study aims to evaluate the clinical effectiveness and cost-effectiveness of intensive community care service (ICCS) compared to treatment as usual (TAU) for young people with psychiatric emergencies. Methods: This is a multicentre two-arm randomized controlled trial (RCT) with an internal pilot phase. Young people aged 12 to < 18 considered for admission at participating NHS organizations across the UK will be randomized 1:1 to either TAU or ICCS. The primary outcome is the time to return to or start education, employment, or training (EET) at 6 months post-randomization. Secondary outcomes will include evaluations of mental health and overall well-being and patient satisfaction. Service use and costs and cost-effectiveness will also be explored. Intention-to-treat analysis will be adopted. The trial is expected to be completed within 42 months, with an internal pilot phase in the first 12 months to assess the recruitment feasibility. A process evaluation using visual semi-structured interviews will be conducted with 42 young people and 42 healthcare workers. Discussion: This trial is the first well-powered randomized controlled trial evaluating the clinical and cost-effectiveness of ICCS compared to TAU for young people with psychiatric emergencies in Great Britain. Trial registration: ISRCTN ISRCTN42999542, Registration on April 29, 202

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Sun exposure and psychotic experiences

Objective:Sun exposure is considered the single most important source of vitamin D. Vitamin D deficiency has been suggested to play a role in the etiology of psychotic disorders. The aim of the present study was to evaluate the association between sun exposure and psychotic experiences (PEs) in a general population sample of Swedish women.Methods:The study population included participants from The Swedish Women’s Lifestyle and Health cohort study. The 20-item community assessment of psychic experiences (CAPEs) was administered between ages 30 and 50 to establish PEs. Sun exposure as measured by (1) sunbathing holidays and (2) history of sunburn was measured between ages 10 and 39. The association between sun exposure and PEs was evaluated by quantile regression models.Results:34,297 women were included in the analysis. Women who reported no sunbathing holidays and 2 or more weeks of sunbathing holidays scored higher on the CAPE scale than women exposed to 1 week of sunbathing holidays across the entire distribution, when adjusting for age and education. Similarly, compared with women who reported a history of one sunburn, the women with none or two or more sunburns showed higher scores on the CAPE scale.Conclusion:The results of the present study suggest that, in a population-based cohort of middle aged women, both low and high sun exposure is associated with increased level of positive PEs