Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

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.

Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study.

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

Education and long-term outcomes in first episode psychosis: 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders. METHODS: Education achievement was explored in a large sample (n = 659) of FEP patients enrolled in programa de atención a fases iniciales de psicosis (PAFIP), a research and assistance program conducted in Spain. Patients were stratified according to the Spanish educational system according to their attendance in primary (low), secondary (medium) or university studies (high). The three groups were compared on available premorbid, clinical and neuropsychological variables. A subgroup of patients (n = 209), comprising the 10-year follow-up PAFIP cohort, were again compared. RESULTS: Overall, 49% and 37% of FEP patients had low and medium levels of education, respectively. In total, 13% of the patients with a higher level of education were more frequently women (64%) and older at illness onset (36 years old), reported better premorbid adjustment, presented less severe positive symptoms and better functioning; and showed higher premorbid intelligence quotient and better performance on all the explored cognitive domains. Ten years later the FEP patients in the medium- and high-education groups had good global functioning and a neurocognitive performance within the normal limits. CONCLUSIONS: Higher education is associated with better initial conditions and more favourable outcomes after an FEP. Sharing this information with the world's educational systems is essential to targeting resources and designing innovative programs or strategies to compensate for student difficulties.

Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. METHODS: Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. RESULTS: The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CONCLUSIONS: CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium.

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

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.

Aripiprazole vs Risperidone Head-to-Head Effectiveness in First-Episode Non-Affective-Psychosis: A 3-Month Randomized, Flexible-Dose, Open-Label Clinical Trial.

BACKGROUND: Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second-generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short term of aripiprazole and risperidone after FEP outbreak. METHODS: From February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode drug-naïve patients were randomly assigned to aripiprazole (n = 136) or risperidone (n = 130) and followed-up for 12 weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. RESULTS: The overall dropout rate at 12 weeks was small (6.39%). Effectiveness measures were similar between treatment arms as treatment discontinuation rates (χ 2 = 0,409; P = .522), and mean time to all-cause discontinuation (log rank χ 2 = -1.009; P = .316) showed no statistically significant differences. Despite no statistically significant differences between groups regarding clinical efficacy, aripiprazole required higher chlorpromazine equivalent dosage (χ 2 = 2.160; P = .032) and extended mean time (W = 8183.5; P = .008) to reach clinical response. Sex-related adverse events and rigidity were more frequent in the risperidone group, whereas sialorrhea was on the aripiprazole group. CONCLUSIONS: No differences regarding effectiveness were found between aripiprazole and risperidone for the short-phase treatment of FEP. Despite the importance of efficacy during this phase, differences in side effect profiles and patient's preferences are essential factors that may lead clinical decisions for these patients. CLINICALTRIALS.GOV: NCT02532491. Effectiveness of Second-Generation Antipsychotics in First Episode Psychosis Patients: 1-year Follow-up (PAFIP3_1Y).

Ten-year course of cognition in first-episode non-affective psychosis patients: PAFIP cohort.

BACKGROUND: A large body of research states that cognitive impairment in schizophrenia is static. Nevertheless, most previous studies lack a control group or have small study samples or short follow-up periods. METHOD: We aimed to address these limitations by studying a large epidemiological cohort of patients with first-episode schizophrenia spectrum disorders and a comparable control sample for a 10-year period. RESULTS: Our results support the generalized stability of cognitive functions in schizophrenia spectrum disorders considering the entire group. However, the existence of a subgroup of patients characterized by deteriorating cognition and worse long-term clinical outcomes must be noted. Nevertheless, it was not possible to identify concomitant factors or predictors of deterioration (all Ps > 0.05). CONCLUSIONS: Cognitive functions in schizophrenia spectrum disorder are stable; however, a subgroup of subjects that deteriorate can be characterized.

Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review.

BACKGROUND: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits. METHODS: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adults with a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomic insertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). We synthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool. RESULTS: Fifty-five studies met the inclusion criteria (45 case-control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variants involved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in COMT, DTNBP1, BDNF and TCF4. Through genome-wide association studies, 2 SNPs in CHD7 and GATAD2A were associated with IQ in patients with SSD. The studies on CNVs suggested significant associations between structural variants and low IQ in patients with SSD. LIMITATIONS: Overall, primary studies used heterogeneous IQ measurement tools and had small samples. Grey literature was not screened. CONCLUSION: Genetic overlap between SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were in genes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.

A family study on first episode of psychosis patients: Exploring neuropsychological performance as an endophenotype.

INTRODUCTION: Family studies provide a suitable approach to analyzing candidate endophenotypes of schizophrenia, including cognitive features. OBJECTIVE: To characterize different neurocognitive functions in a group of patients with first episode of psychosis (FEP), their first-degree relatives (parents and siblings), and healthy controls (HC), in order to identify potential endophenotypes for schizophrenia spectrum disorders (SSD). METHODS: Participants were assessed in the context of a national project in Spain called PAFIP-FAMILIAS. They completed the same neuropsychological battery, which included tests of verbal memory, visual memory, processing speed, working memory, executive functions, motor dexterity, attention, and theory of mind. Group comparisons were performed using one-way ANOVA, followed by tests of multiple comparisons when appropriate. RESULTS: One hundred thirty-three FEP patients were included, as well as 244 of their first-degree relatives (146 parents and 98 siblings) and 202 HC. In general, relatives showed an intermediate performance between the HC and the FEP patients in all neurocognitive domains. However, the domains of executive functions and attention stood out, as relatives (especially parents) showed similar performance to FEP patients. This was replicated when selecting patients subsequently diagnosed with schizophrenia and their relatives. CONCLUSION: These findings suggest that executive and attention dysfunctions might have a family aggregation and could be relevant cognitive endophenotypes for psychotic disorders. The study shows the potential of exploring intra-family neuropsychological performance supporting neurobiological and genetic research in SSD.

Disentangling early and late onset of psychosis in women: identifying new targets for treatment.

Women present a second peak of incidence of psychosis during the menopausal transition, partially explained by the loss of estrogen protection conferred during the reproductive years. In view of the lack of studies comparing sociodemographic, biological, and clinical variables and neurocognitive performance between women with early onset of psychosis (EOP) and those with late onset of psychosis (LOP), our aim was to characterize both groups in a large sample of 294 first-episode psychosis (FEP) patients and 85 healthy controls (HC). In this cross-sectional study, the participants were interviewed to gather information on sociodemographic variables. We assessed laboratory features of interest and conducted a clinical assessment of psychopathological symptoms and neurocognitive abilities. From the latter, we derived a global cognitive functioning score. Analysis of covariance (ANCOVA) was used to compare EOP and LOP groups, and each group with age-comparable HC. EOP women were more frequently single and unemployed than HC age peers. While cholesterol levels in LOP women were higher than those in EOP women, no statistically significant differences were found in leptin levels. Women with LOP presented with less severe negative symptoms and higher cognitive processing speed scores than women with EOP. Cannabis and alcohol use was greater in EOP than in LOP women. Within the total FEP group, there was a history of significantly more recent traumatic events than in the HC group. Women with EOP and LOP show several sociodemographic and clinical differences, which may be valuable for planning personalized treatment.

Treatment Discontinuation Impact on Long-Term (10-Year) Weight Gain and Lipid Metabolism in First-Episode Psychosis: Results From the PAFIP-10 Cohort.

BACKGROUND: Patients with a first episode of psychosis (FEP) are at higher risk of gaining weight and presenting metabolic disturbances, partly related to antipsychotic exposure. Previous studies suggest that treatment discontinuation might have a positive impact on weight in schizophrenia. The aim of this study was to evaluate the effect of treatment discontinuation on weight and metabolic changes in a FEP cohort. METHODS: A total of 209 FEP patients and 57 healthy controls were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric measures and, clinical, metabolic, and sociodemographic data were collected. RESULTS: Patients discontinuing antipsychotic treatment presented a significantly lower increase in weight and better metabolic parameter results than those still on antipsychotic treatment at 10-year follow-up. CONCLUSIONS: Treatment discontinuation had a positive effect on the weight and metabolic changes observed in FEP patients; however, this effect was not sufficient to reaching a complete reversal to normal levels.

Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.

BACKGROUND: The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. METHOD: A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. RESULTS: The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. CONCLUSIONS: The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Predictors of diagnostic stability in brief psychotic disorders: Findings from a 3-year longitudinal study.

INTRODUCTION: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. METHODS: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria was explored in a large epidemiological cohort (n = 569) of non-affective first-episode psychosis (FEP) patients enrolled in a three-year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. RESULTS: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM-IV criteria for BPD, of whom 40 completed the three-year follow-up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. CONCLUSION: Our findings confirm that BPD is a clinical condition with moderate-to-low temporal stability and demonstrate that approximately two-thirds of FEP individuals experiencing BPD will develop a long-lasting psychotic disorder during follow-up, mainly schizophrenia.

Stability of schizophrenia diagnosis in a 10-year longitudinal study on first episode of non-affective psychosis: Conclusions from the PAFIP cohort.

OBJECTIVE: To evaluate the 10-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. METHODS: Changes in diagnosis of 209 FEP patients were described during 10 years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. RESULTS: Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the 10-year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. CONCLUSIONS: Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years.

Cognitive training with modern board and card games in healthy older adults: two randomized controlled trials.

OBJECTIVES: The aim of this study was to assess the effectiveness of a cognitive intervention based on modern board and card games. METHODS: We conducted two two-arm parallel-group, randomized controlled trials. The first one (pilot study) was nonblind. The second one (main study) was a double-blind design. Participants (14 in a pilot study and 35 in the main study) were healthy older adults over 65 years old who were assisting to adult care institutions. In the pilot study, participants in the experimental group (n = 6) played modern board and card games which activated cognitive processes; whereas the control group (n = 6) was in the wait-list condition. In the main study, participants in the experimental group (n = 12) also played modern board and card games; whereas the control group (n = 15) performed standardized paper-and-pencil cognitive tasks. Psychologists specialized in older-people conducted all the interventions. In both studies, intervention sessions were bi-weekly for 5 weeks. The outcomes of both studies were cognitive status and executive functioning, depressive symptomatology, and quality of life measures. All assessment and intervention sessions took place in their habitual centers. RESULTS: In the pilot study, participants in the games intervention showed a significant improvement in semantic verbal fluency. In the main study, both interventions showed significant improvements in phonemic verbal fluency. Whilst board and card games maintained motor impulsivity control, paper-and-pencil tasks improved speed in an inhibition task. CONCLUSIONS: Modern board and card games could be an effective cognitive intervention to maintain some cognitive functions.

Health Education Intervention for Patients Undergoing Placement of Percutaneous Nephrostomy Tube: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the economic impact (cost) of percutaneous nephrostomy (PCN) tube care in patients following an educational intervention to no intervention. DESIGN: A randomized controlled trial. SUBJECTS AND SETTING: The sample comprised 178 patients recruited between May 2017 and April 2019. The study setting was the Marqués de Valdecilla University Hospital located in Cantabria on the northern coast of Spain. Data were collected in the hospital's radiology department. METHODS: Participants were randomly allocated to 2 groups: an intervention group received an educational intervention that specifically addressed living with a PCN tube and a control group that received standard instruction. The intervention group received the educational intervention twice, before placement of the nephrostomy and at first tube change (6 weeks later). The main outcome variable was economic impact of the PCN, operationally defined as unscheduled or urgent visits and health care costs related to PCN tube placement. RESULTS: When compared to control group subjects, participants who received the educational intervention had fewer urgent (unscheduled) visits (1.9 vs 4.0; P = .004) and lower direct and indirect health care costs reflecting a savings of €5277 (approximately US $6257). CONCLUSIONS: The health education intervention reduced costs associated with these additional visits when compared to patients receiving standard postprocedural education.

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.

BACKGROUND: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. CONCLUSIONS: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.