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.

BACKGROUND: Endovascular 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. METHODS: The 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. DISCUSSION: This 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 REGISTRATION: ISRCTN13832085. Dec. 3, 2021.

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, 2020.

Intensive community care services for children and young people in psychiatric crisis: an expert opinion.

BACKGROUND: Children and young people's (CYP) mental health is worsening, and an increasing number are seeking psychiatric and mental health care. Whilst many CYPs with low-to-medium levels of psychiatric distress can be treated in outpatient services, CYPs in crisis often require inpatient hospital treatment. Although necessary in many cases, inpatient care can be distressing for CYPs and their families. Amongst other things, inpatient stays often isolate CYPs from their support networks and disrupt their education. In response to such limitations, and in order to effectively support CYPs with complex mental health needs, intensive community-based treatment models, which are known in this paper as intensive community care services (ICCS), have been developed. Although ICCS have been developed in a number of settings, there is, at present, little to no consensus of what ICCS entails. METHODS: A group of child and adolescent mental health clinicians, researchers and academics convened in London in January 2023. They met to discuss and agree upon the minimum requirements of ICCS. The discussion was semi-structured and used the Dartmouth Assertive Community Treatment Fidelity Scale as a framework. Following the meeting, the agreed features of ICCS, as described in this paper, were written up. RESULTS: ICCS was defined as a service which provides treatment primarily outside of hospital in community settings such as the school or home. Alongside this, ICCS should provide at least some out-of-hours support, and a minimum of 90% of CYPs should be supported at least twice per week. The maximum caseload should be approximately 5 clients per full time equivalent (FTE), and the minimum number of staff for an ICCS team should be 4 FTE. The group also confirmed the importance of supporting CYPs engagement with their communities and the need to remain flexible in treatment provision. Finally, the importance of robust evaluation utilising tools including the Children's Global Assessment Scale were agreed. CONCLUSIONS: This paper presents the agreed minimum requirements of intensive community-based psychiatric care. Using the parameters laid out herein, clinicians, academics, and related colleagues working in ICCS should seek to further develop the evidence base for this treatment model.

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

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.

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.

Dissociative seizures resemble epileptic seizures or faints, but can be distinguished from them by trained doctors. Dissociation is the medical word for a 'trance-like' or 'switching off' state. People with dissociative seizures commonly have other psychological or physical problems. Quality of life may be low. The condition accounts for about one in every six patients seen in hospitals because of seizures. We wanted to find out if people with dissociative seizures receiving standardised treatment would also benefit from a talking therapy, called cognitive­behavioural therapy, made specific to this disorder. We did a randomised controlled trial to find out if people with dissociative seizures given standardised treatment and cognitive­behavioural therapy (talking therapy) would do better than those given standardised treatment alone. Standardised treatment of dissociative seizures began with careful diagnosis from a neurologist and then further assessment and treatment from a psychiatrist. In total, 368 people with dissociative seizures participated, with half receiving standardised treatment alone and half having talking therapy plus standardised treatment. We measured seizures and psychological and physical health in both trial groups. We also investigated whether or not cognitive­behavioural therapy was good value for money. After 12 months, patients in both trial groups seemed to have fewer monthly seizures, but there was no advantage in the talking therapy group. Patients in the talking therapy group had more consecutive days without seizures, reporting less impact from them in everyday situations. Patients in the talking therapy group, and their doctors, considered improvements to be better, and patients in this group reported greater satisfaction with treatment. However, the talking therapy was expensive and not as cost-effective as hoped. Interviews with patients and study clinicians showed that they valued aspects of both treatments and of the care provided by the multidisciplinary teams. Overall, cognitive­behavioural therapy designed for dissociative seizures plus standardised treatment was not better at reducing the total numbers of seizures reported, but did produce several positive benefits for participants compared with standardised treatment alone.

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 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.

The experiences of therapists providing cognitive behavioral therapy (CBT) for dissociative seizures in the CODES randomized controlled trial: A qualitative study.

OBJECTIVES: Little is known about the experiences of therapists delivering psychotherapy for patients with dissociative seizures (DS), a complex disorder associated with a range of comorbid psychosocial and mental health difficulties. This study set out to explore therapists' experiences of delivering DS-specific, manualized cognitive behavioral therapy (CBT) to adults with DS within the context of a randomized control trial. METHODS: Interviews were conducted with 12 therapists involved in the COgnitive behavioral therapy vs standardized medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial and were analyzed using thematic framework analysis (TFA). RESULTS: Six main themes emerged, namely 1) aspects of the intervention that were favored, while others were not always considered applicable; 2) multiple and complex difficulties faced by patients; 3) working effectively within the protocol; 4) limitations of the protocol; 5) significance of formulation; and 6) quality of standardized medical care (SMC) and difficulties of diagnosis delivery. These addressed valued aspects of the intervention, complexities of the patient group, and experiences working within a structured treatment protocol. Family involvement and psychoeducation were highlighted as important components; the applicability of graded exposure techniques, however, was restricted by patients' apparent emotional avoidance. The structure provided by the treatment protocol was valued, but flexibility was important to individualize treatment in complex cases. A comprehensive formulation was fundamental to this. The initial diagnostic explanation provided by neurologists and psychiatrists was generally considered beneficial, with patients often perceived to enter therapy with a better understanding of their condition. CONCLUSIONS: This study demonstrated that the DS-specific CBT intervention met with general approval from therapists who also highlighted some practical challenges. Because of the nature of the condition, the need for experience of working with complex patients should be considered when applying the intervention to individual cases. Setting the CBT intervention in the context of a structured care pathway involving neurology and psychiatry may facilitate the therapeutic process.

Characteristics of 698 patients with dissociative seizures: A UK multicenter study.

OBJECTIVE: We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. METHODS: We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non-Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. RESULTS: In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self-reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two-thirds were unemployed. SIGNIFICANCE: Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Cognitive Change in Schizophrenia and Other Psychoses in the Decade Following the First Episode.

OBJECTIVE: Schizophrenia is associated with a marked cognitive impairment that is widely believed to remain stable after illness onset. Yet, to date, 10-year prospective studies of cognitive functioning following the first episode with good methodology are rare. The authors examined whether schizophrenia patients experience cognitive decline after the first episode, whether this decline is generalized or confined to individual neuropsychological functions, and whether decline is specific to schizophrenia. METHODS: Participants were from a population-based case-control study of patients with first-episode psychosis who were followed prospectively up to 10 years after first admission. A neuropsychological battery was administered at index presentation and at follow-up to patients with a diagnosis of schizophrenia (N=65) or other psychoses (N=41) as well as to healthy comparison subjects (N=103). RESULTS: The schizophrenia group exhibited declines in IQ and in measures of verbal knowledge and of memory, but not processing speed or executive functions. Processing speed and executive function impairments were already present at the first episode and remained stable thereafter. The magnitude of declines ranged between 0.28 and 0.66 standard deviations. Decline in measures of memory was not specific to schizophrenia and was also apparent in the group of patients with other psychoses. Healthy individuals with low IQ showed no evidence of decline, suggesting that a decline is specific to psychosis. CONCLUSIONS: Patients with schizophrenia and other psychoses experience cognitive decline after illness onset, but the magnitude of decline varies across cognitive functions. Distinct mechanisms consequent to the illness and/or psychosocial factors may underlie impairments across different cognitive functions.

Neuropsychological function at first episode in treatment-resistant psychosis: findings from the ÆSOP-10 study.

BACKGROUND: Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis. METHODS: We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up. RESULTS: Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = -2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = -2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01-0.001) and those born outside the UK (p values<0.05). CONCLUSIONS: Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable - at a group level - at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

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.

Biological motion processing in schizophrenia - Systematic review and meta-analysis.

CONTEXT: Patients with schizophrenia show impairments in processing of biological motion. This is especially important since deficits in domains of social cognition has been associated with functional outcome and everyday functioning in this population. OBJECTIVES: We conducted a systematic review and meta-analysis of studies which have used point-light displays to present whole-body motion to patients with schizophrenia and healthy controls, to evaluate the magnitude of differences between these groups in biological motion processing. METHOD: Firstly, relevant publications were identified by a systematic search of Google Scholar and PubMed databases. Secondly, we excluded non-relevant studies for the meta-analysis according to our exclusion criteria. Effect sizes were expressed as standardized mean difference (SMD). RESULTS: 15 papers reporting results of 14 different experiments with 571 patients and 482 controls were included in the meta-analysis. The results for the general biological motion perception analysis revealed that patients with schizophrenia (compared with healthy controls) present reduced biological motion processing capacity with the effect size (SMD) of 0.66 (95% CI, -0.79 to -0.54; p<0.001). The results for the specific biological motion-based tasks were also statistically significant with SMD of 0.72 for Basic Biological Motion task (95% CI: -0.94 to -0.51; p<0.001) and SMD of 0.61 for Emotion in Biological Motion task, (95% CI: -0.79 to -0.43; p<0.001) respectively. CONCLUSION: The findings from our meta-analysis highlight abnormalities in general and specific domains of biological motion perception in schizophrenia patients as compared with healthy controls.

Psychotic Experiences and Neuropsychological Functioning in a Population-based Sample.

IMPORTANCE: Psychotic experiences in early life are associated with neuropsychological impairment and the risk for later psychiatric disorders. Psychotic experiences are also prevalent in adults, but neuropsychological investigations spanning adulthood are limited, and confounding factors have not been examined rigorously. OBJECTIVE: To characterize neuropsychological functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and familial factors and investigating the effect of age. DESIGN, SETTING, AND PARTICIPANTS: The South East London Community Health (SELCoH) study is a population-based household survey of physical and mental health in individuals 16 years or older conducted from June 1, 2008, to December 31, 2010, in 2 London boroughs. The study included 1698 participants from 1075 households. Data were analyzed from May 6, 2014, to April 22, 2015. EXPOSURES: Psychotic experiences measured using the Psychosis Screening Questionnaire. MAIN OUTCOMES AND MEASURES: Neuropsychological functioning measured using tests assessing verbal knowledge (Wechsler Test of Adult Reading), working memory (Spatial Delayed Response Task), memory (Visual Object Learning Task), and processing speed (digit symbol coding task). A composite IQ score of general cognitive ability was calculated. RESULTS: A total of 1677 participants with a mean (SD) age of 40 (17) years were included in the analysis. Compared with the group without psychotic experiences, the 171 (9.7%) adults with psychotic experiences did not show a statistically significant impairment on mean (SD) measures of IQ (95.25 [16.58] vs 100.45 [14.77]; Cohen d, -0.22; P = .06) or processing speed (40.63 [13.06] vs 42.17 [13.79]; Cohen d, -0.03; P = .73) but were impaired on measures of verbal knowledge (31.36 [15.78] vs 38.83 [12.64]; Cohen d, -0.37; P = .003), working memory (20.97 [4.12] vs 22.51 [3.26]; Cohen d, -0.34; P = .005), and memory (43.80 [8.45] vs 46.53 [7.06]; Cohen d, -0.28; P = .01). Only participants 50 years and older with psychotic experiences showed medium to large impairments in neuropsychological functioning (mean [SD]) on measures of IQ (81.22 [15.97] vs 91.28 [14.31]; Cohen d, -0.70), verbal knowledge (28.31 [13.83] vs 38.51 [11.50]; Cohen d, -0.88), working memory (19.11 [4.77] vs 21.99 [3.42]; Cohen d, -0.82), and memory (39.17 [8.23] vs 44.09 [6.51]; Cohen d, -0.45) after adjusting for socioeconomic status, cannabis use, and common mental disorders. Medium impairments (mean [SD]) on measures of working memory (21.27 [3.64] vs 22.62 [2.97]; Cohen d, -0.45) and memory (44.32 [5.84] vs 46.91 [5.74]; Cohen d, -0.45) were seen in those aged 35 to 49 years and on a measure of verbal knowledge (30.81 [14.17] vs 37.60 [10.48]; Cohen d, -0.62) in those aged 16 to 24 years. First-degree relatives of adults with psychotic experiences showed a small impairment on a measure of verbal knowledge (34.71 [12.10] vs 38.63 [10.97]; Cohen d, -0.36; P = .02), and unrelated cohabitants showed no neuropsychological impairment. CONCLUSIONS AND RELEVANCE: The profile of cognitive impairment in adults with psychotic experiences differed from that seen in adults with psychotic disorders, suggesting important differences between subclinical and clinical psychosis.

Gender differences in neuropsychological performance across psychotic disorders--a multi-centre population based case-control study.

BACKGROUND: Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance. METHODS: Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared. RESULTS: There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences. CONCLUSIONS: Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.