Validity and reliability of the Brazilian version of the Cognitive Reserve Assessment Scale in Health

Cognitive reserve; Cognition; Validation studyReserva cognitiva; Cognición; Estudio de validaciónReserva cognitiva; Cognició; Estudi de validacióOBJECTIVE: As the older population increases, it is important to identify factors that may reduce the risks of dementia in the general population. One such factor is the concept of cognitive reserve (CR). The present study analyzed the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in the Brazilian population. This scale was originally developed to measure CR in individuals with severe mental illness. We also investigated the relationship between the CRASH and clinical or sociodemographic variables. METHODS: This study was conducted with 398 individuals. We assessed sociodemographic variables and depression, anxiety, and stress symptoms (Depression, Anxiety and Stress Scale [DASS-21]) using a web-based survey. We constructed a confirmatory factor analysis (CFA) model in order to test the goodness of fit of the factor structure proposed in the original CRASH study. RESULTS: The McDonald's hierarchical ω for CRASH using CFA parameters was 0.61, and the Cronbach's alpha coefficient indicated good internal consistency when considering all items (alpha = 0.7). CONCLUSIONS: Our results suggest that CRASH can be used to assess CR in the general population in Brazil.This work has received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and was financed in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES), Finance Code 001. SA has been supported by a Sara Borrell contract (CD20/00177) funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Social Fund "Investing in your future." EV has received funding from the Spanish Ministry of Science, Innovation and Universities (PI15/00283; PI21/00787) integrated into the Plan Nacional de I+D+I and was co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya to the Bipolar Disorders Group (2017 SGR 1365), and project SLT006/17/00357 from Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Departament de Salut), Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya. DBS has received financial support from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). JFG has received financial support from CAPES. ARR has received financial support from CNPq for the PQ 2019 productivity scholarship 302382/2019-4

Identifying pathways between psychiatric symptoms and psychosocial functioning in the general population

The present study aims to identify pathways between psychiatric network symptoms and psychosocial functioning and their associated variables among functioning clusters in the general population. A cross-sectional web-based survey was administered in a total of 3,023 individuals in Brazil. The functioning clusters were derived by a previous study identifying three different groups based on the online Functioning Assessment Short Test. Networking analysis was fitted with all items of the Patient-Reported Outcomes Measurement Information System for depression and for anxiety (PROMIS) using the mixed graphical model. A decision tree model was used to identify the demographic and clinical characteristics of good and low functioning. A total of 926 (30.63%) subjects showed good functioning, 1,436 (47.50%) participants intermediate functioning, and 661 (21.86%) individuals low functioning. Anxiety and uneasy symptoms were the most important nodes for good and intermediate clusters but anxiety, feeling of failure, and depression were the most relevant symptoms for low functioning. The decision tree model was applied to identify variables capable to discriminate individuals with good and low functioning. The algorithm achieved balanced accuracy 0.75, sensitivity 0.87, specificity 0.63, positive predictive value 0.63 negative predictive value 0.87 (p<0.001), and an area under the curve of 0.83 (95%CI:0.79–0.86, p<0.01). Our results show that individuals who present psychological distress are more likely to experience poor functional status, suggesting that this subgroup should receive a more comprehensive psychiatric assessment and mental health care

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination

Toward precision psychiatry in bipolar disorder : staging 2.0

Personalized treatment is defined as choosing the “right treatment for the right person at the right time.” Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current stagingmodels integratemultiple levels of information that can help to define each patient’s characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient’s stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models

Self-reported neurocognitive symptoms during COVID-19 lockdown and its associated factors in a sample of psychiatric patients. Results from the BRIS-MHC study

Lockdown caused by COVID-19 pandemic has a negative impact on mental health. The aim was to assess self-reported neurocognitive symptoms during the lockdown and identify associated vulnerable and protective factors in a sample of psychiatric patients in a Spanish population.These results are part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRISMHC) project. Neurocognitive symptoms were assessed through an online survey considering the five items that represented self-reported neurocognitive complaints. We split the sample into two groups based on the severity of the self-reported neurocognitive complaints: intact cognitive function/mild cognitive impairment (CI-) and moderate/severe cognitive impairment (CI+). Univariate analyses were used to compare both groups in terms of sociodemographic and clinical variables. Multiple logistic regression models were carried out to identify clinical variables and coping strategies associated with neurocognitive symptoms. 198 patients with different psychiatric diagnoses were included in this study. One hundred seventeen patients were classified in the CI- group and 81 in the CI+ group. Depressive symptoms and negative psychotic-like symptoms were vulnerable factors for neurocognitive impairment. Coping strategies of performing physical activity, carrying out relaxing activities and maintaining a routine were protective factors against cognitive impairment. Lockdown situation negatively impact on neurocognitive function. Psychopathological symptoms and coping strategies were associated with neurocognitive symptoms during lockdown in subjects with psychiatric illness. The early treatment of psychopathological symptoms in psychiatric patients and promoting coping strategies during lockdown should be considered an intervention strategy against cognitive impairment

Combining MRI and clinical data to detect high relapse risk after the first episode of psychosis.

Detecting patients at high relapse risk after the first episode of psychosis (HRR-FEP) could help the clinician adjust the preventive treatment. To develop a tool to detect patients at HRR using their baseline clinical and structural MRI, we followed 227 patients with FEP for 18-24 months and applied MRIPredict. We previously optimized the MRI-based machine-learning parameters (combining unmodulated and modulated gray and white matter and using voxel-based ensemble) in two independent datasets. Patients estimated to be at HRR-FEP showed a substantially increased risk of relapse (hazard ratio=4.58, P<0.05). Accuracy was poorer when we only used clinical or MRI data. We thus show the potential of combining clinical and MRI data to detect which individuals are more likely to relapse, who may benefit from increased frequency of visits, and which are unlikely, who may be currently receiving unnecessary prophylactic treatments. We also provide an updated version of the MRIPredict software.We would also like to thank the Instituto de Salud Carlos III, the Spanish Ministry of Science, Innovation, and Universities, the European Regional Development Fund (ERDF/FEDER), European Social Fund, “Investing in your future”, “A way of making Europe” (projects: PI08/0208, PI11/00325, PI14/00292, PI14/00612, PI14/01148, PI14/01151, PI17/00481, PI17/01997, PI18/01055, PI19/00394, PI19/00766, PI20/00721, PI20/01342, and PI21/00713; contracts: CP14/00041, JR19/00024, CPII19/00009, and CD20/00177); CERCA Program; Catalan Government, the Secretariat of Universities and Research of the Department of Enterprise and Knowledge (2017SGR01271, 2017SGR1355, and 2017SGR1365); Institut de Neurociències, Universitat de Barcelona; Madrid Regional Government (B2017/BMD-3740 AGES-CM-2); the University of the Basque Country (2019 321218ELCY GIC18/107); the Basque Government (2017111104); European Union Structural Funds, European Union Seventh Framework Program, European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. The funding organizations played no role in the study design, data collection, analysis, or manuscript approval

Cortical thinning over two years after first-episode psychosis depends on age of onset.

[EN] First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d=0.54; p=002). In a post-hoc-analysis, adolescent-onset (≤19y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.We are extremely grateful to all subjects who took part in this study. This work was supported by CIBERSAM; Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI081203, PI08/0208; PI11/00325; PI1101686, PI14/00612, PI17/01997, PI20/01342), co‐financed by the ERDF from the European Commission “A way of making Europe”, European Union Seventh Framework Program (FP7- HEALTH-2013-2.2.1-2-603196 [Project PSYSCAN]), EU H2020 (IMI‐2 Joint Undertaking under grant agreements 115916 (project PRISM) and 777394 (project AIMS‐2‐TRIALS)), Madrid Regional Government (S2017/BMD‐3740, and AGES-CM-2-CM) and European Union Structural Funds; Fundación Familia Alonso, Fundacion Mutua Madrileña, and Fundación Alicia Koplowitz

Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode

Background Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder. Methods The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status. Results Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001). Conclusions Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent

High-resolution dietary reconstruction of victims of the 79 CE Vesuvius eruption at Herculaneum by compound-specific isotope analysis.

The remains of those who perished at Herculaneum in 79 CE offer a unique opportunity to examine lifeways across an ancient community who lived and died together. Historical sources often allude to differential access to foodstuffs across Roman society but provide no direct or quantitative information. By determining the stable isotope values of amino acids from bone collagen and deploying Bayesian models that incorporate knowledge of protein synthesis, we were able to reconstruct the diets of 17 adults from Herculaneum with unprecedented resolution. Significant differences in the proportions of marine and terrestrial foods consumed were observed between males and females, implying that access to food was differentiated according to gender. The approach also provided dietary data of sufficient precision for comparison with assessments of food supply to modern populations, opening up the possibility of benchmarking ancient diets against contemporary settings where the consequences for health are better understood