Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: Results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio-economic development of the country or the specific health care systemThis work was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, Madrid Regional Government (S2010/BMD- 2422 AGES), European Union Structural Funds, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, ERA-NET NEURON (Network of European Funding for Neuroscience Research) and theWorld Health Organizatio

Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder

Introduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence. Methods: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland–Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis. Results: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [−8.1%, 16.74%]; no subgroup differences χ(2) = 1.24, p-value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [−0.87, 1.04]; χ(2) = 0.02, p-value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used. Discussion: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed

Cognition and functionality in delusional disorder.

BACKGROUND: Even if neurocognition is known to affect functional outcomes in schizophrenia, no previous study has explored the impact of cognition on functionality in delusional disorder (DD). We aimed to assess the effect of clinical characteristics, symptom dimensions and neuropsychological performance on psychosocial functioning and self-perceived functional impairment in DD. METHODS: Seventy-five patients with a SCID-I confirmed diagnosis of DD underwent neurocognitive testing using a neuropsychological battery examining verbal memory, attention, working memory and executive functions. We assessed psychotic symptoms with the Positive and Negative Syndrome Scale, and calculated factor scores for four clinical dimensions: Paranoid, Cognitive, Affective and Schizoid. We conducted hierarchical linear regression models to identify predictors of psychosocial functioning, as measured with the Global Assessment of Functioning scale, and self-perceived functional impairment, as measured with the Sheehan's Disability Inventory. RESULTS: In the final linear regression models, higher scores in the Paranoid (β= 0.471, p < .001, r2 = 0.273) and Cognitive (β = 0.325, p < .001, r2 = 0.180) symptomatic dimensions and lower scores in verbal memory (β = -0.273, p < .05, r2 = 0.075) were significantly associated with poorer psychosocial functioning in patients with DD. Lower scores in verbal memory (β= -0.337, p < .01, r2 = 0.158) and executive functions (β= -0.323, p < .01, r2 = 0.094) were significantly associated with higher self-perceived disability. CONCLUSIONS: Impaired verbal memory and cognitive symptoms seem to affect functionality in DD, above and beyond the severity of the paranoid idea. This suggests a potential role for cognitive interventions in the management of DD

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

Objective: To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis. Method: Fifty adolescents (age 16 ± 1.25) with a first episode of psychosis were randomized to quetiapine or olanzapine in a 6-month open label study. Efficacy and side effect scales, as well as vital signs and laboratory data were recorded at baseline, 7, 15, 30, 90, and 180 days (end of study). Results: Out of the total sample included in the study, 32 patients completed the trial (quetiapine n = 16, olanzapine n = 16). Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale (PANSS) for olanzapine and the general psychopathology scale of the PANSS for quetiapine. The only difference between treatment arms on the clinical scales was observed on the patients' strength and difficulties questionnaire (SDQ) scale, with greater improvement for olanzapine. Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg. Conclusion: Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample. Patients on olanzapine gained significantly more weight. Side effects with both drugs seemed to be more prevalent than those reported in adult studies

Pilot study of an online intervention for young people with a first psychotic episode: Thinkapp

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Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions

Economic analysis of early intervention for autistic children: findings from four case studies in England, Ireland, Italy and Spain

Background: Many autistic children experience difficulties in their communication and language skills development, with consequences for ’social development into adulthood, often resulting in challenges over the life-course and high economic impacts for individuals, families and society. The PACT (Preschool-Autism-Communication-Trial) intervention is effective in terms of improved social communication and some secondary outcomes. A previously published within-trial economic analysis found that results at 13 months did not support its cost-effectiveness. We modelled cost-effectiveness over 6 years and across four European countries. Methods: Using simulation modelling, we built on economic analyses in the original trial, exploring longer-term cost-effectiveness at 6 years (in England). We adapted our model to undertake an economic analysis of PACT in Ireland, Italy and Spain. Data on resource use were taken from the original trial and a more recent Irish observational study. Results: PACT is cost-saving over time from a societal perspective, even though we confirmed that, at 13 months post-delivery, PACT is more expensive than usual treatment (across all countries) when given to preschool autistic children. After 6 years, we found that PACT has lower costs than usual treatment in terms of unpaid care provided by parents (in all countries). Also, if we consider only out-of-pocket expenses from an Irish study, PACT costs less than usual treatment. Discussion: PACT may be recommended as a cost-saving early intervention for families with an autistic child