Artigos e Materiais de Revistas Científicas - FM/MPS
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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.
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- Sociodemographic and clinical characteristics of people with oldest older age bipolar disorder in a global sample: Results from the global aging and geriatric experiments in bipolar disorder project(2024) CHEN, Peijun; SAJATOVIC, Martha; BRIGGS, Farren B. S.; MULSANT, Benoit; DOLS, Annemiek A.; GILDENGERS, Ariel; YALA, Joy; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; REJ, Soham; FORLENZA, Orestes V.; JIMENEZ, Esther; SCHOUWS, Sigfried; ORHAN, Melis; SUTHERLAND, Ashley N.; VIETA, Eduard; TSAI, Shangying; SARNA, Kaylee; EYLER, Lisa T.Objects: Studies of older age bipolar disorder (OABD) have mostly focused on ""younger old"" individuals. Little is known about the oldest OABD (OOABD) individuals aged >= 70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. Methods: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and >= 70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD.
- Networks of Neurodevelopmental Traits, Socioenvironmental Factors, Emotional Dysregulation in Childhood, and Depressive Symptoms Across Development in Two UK Cohorts(2023) FARHAT, Luis C.; BLAKEY, Rachel; SMITH, George Davey; FUJITA, Andre; SHEPHARD, Elizabeth; STERGIAKOULI, Evie; ELEY, Thalia C.; THAPAR, Anita; POLANCZYK, Guilherme V.Objective: Previous population-based studies have identified associations between childhood neurodevelopmental traits and depression in childhood, adolescence, and young adulthood. However, neurodevelopmental traits are highly correlated with each other, which could confound associations when traits are examined in isolation. The authors sought to identify unique associations between multiple neurodevelopmental traits in childhood and depressive symptoms across development, while taking into account co-occurring difficulties, in multivariate analyses. Methods: Data from two U.K. population-based cohorts, the Twins Early Development Study (TEDS) (N=4,407 independent twins) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=10,351), were independently analyzed. Bayesian Gaussian graphical models were estimated to investigate pairwise conditional associations between neurodevelopmental traits (autism and ADHD symptoms and general cognitive, learning, and communication abilities), socioenvironmental stressors (academic performance and peer relations), and emotional dysregulation in childhood (ages 7-11) and depressive symptoms across development (ages 12, 16, and 21). Results: In both cohorts, bivariate correlations indicated several associations between neurodevelopmental traits and depressive symptoms across development. However, based on replicated findings across cohorts, these pairs of variables were mostly conditionally independent, and none were conditionally associated, after accounting for socioenvironmental stressors and emotional dysregulation. In turn, socioenvironmental stressors and emotional dysregulation were conditionally associated with both neurodevelopmental traits and depressive symptoms. Based on replicated findings across cohorts, neurodevelopmental traits in childhood could be associated only indirectly with depressive symptoms across development. Conclusions: This study indicates that associations between childhood neurodevelopmental traits and depressive symptoms across development could be explained by socioenvironmental stressors and emotional dysregulation. The present findings could inform future research aimed at the prevention of depression in youths with neurodevelopmental disorders.
- Unravelling the landscape of Cannabis craving pharmacological treatments: a PRISMA-guided review of evidence(2023) PRETO, Mayra Cruz; KORTAS, Guilherme Trevizan; BLAAS, Israel Kanaan; LASSI, Dangela Layne Silva; CAMPOS, Marcela Waisman; TORALES, Julio; VENTRIGLIO, Antonio; PERICO, Cintia de Azevedo-Marques; ANDRADE, Arthur Guerra de; CASTALDELLI-MAIA, Joao MauricioCurrently, few treatments are available for craving in general, and none of them have received approval for cannabis craving. The objective of this review is to evaluate existing studies analysing treatments for cannabis craving and explore novel treatment possibilities for these patients. The study followed PRISMA guidelines and conducted an extensive database search. Inclusion criteria included human randomised controlled trials examining drug effects on craving symptoms. Exclusion criteria involved studies unrelated to craving, non-pharmacological treatments, duplicates, and non-English/Spanish/Portuguese articles. Our included 22 studies that investigated a wide range of compounds used for cravings related to other drugs, as well as interventions based on healthcare professionals' empirical knowledge. The current pharmacological treatments largely involve off-label drug use and the utilisation of cannabinoid-based medications, such as combinations of THC and lofexidine, oxytocin, progesterone, and N-acetylcysteine. These emerging treatments show promise and have the potential to revolutionise current clinical practices, but further investigation is needed to establish their efficacy. In this context, it is essential to consider non-pharmacological interventions, such as psychotherapy and behavioural treatments. These approaches play a crucial role in complementing pharmacological interventions and addressing the complex nature of the disorder.
- Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder A Systematic Review and Meta-Analysis(2024) FARHAT, Luis C.; FLORES, Jose M.; AVILA-QUINTERO, Victor J.; POLANCZYK, Guilherme V.; CIPRIANI, Andrea; FURUKAWA, Toshi A.; BLOCH, Michael H.; CORTESE, SamueleImportance: Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear.Objective: To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses.Data sources: Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions.Study selection: Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD.Data extraction and synthesis: Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses.Main outcome measures: Change in ADHD symptoms and discontinuations due to adverse events.Results: A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence).Conclusions and relevance: Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.
- Is self-reported 7-day point prevalence abstinence an useful measure for smoking cessation effectiveness among individuals with mental disorders?(2023) LIMA, Danielle Ruiz; DAVANSO, Lucas Carvalho; CARVALHO, Carlos Felipe Cavalcanti; GUIMARAES-PEREIRA, Bruna Beatriz Sales; LORETO, Aline Rodrigues; FRALLONARDO, Fernanda Piotto; ISMAEL, Flavia; ANDRADE, Arthur Guerra de; CASTALDELLI-MAIA, Joao MauricioSmoking rates among individuals with mental disorders are higher compared to general population. We aimed to investigate the effectiveness of a smoking cessation treatment among individuals with and without mental disorders. Self-report 7-day point prevalence was used to assess abstinence status among 'intention to treat' (n = 1,213) and 'completers-only' (n = 578) samples. Participants were distributed in (1) ND-only; (2) ND and other substance use disorder (ND-SUD); (3) ND associated with mental disorder but no other SUD (ND-MD); and (4) co-morbid ND, SUD and MD (ND-SUMD). The treatment program was composed by six weeks of group Cognitive Behavioral Therapy (CBT) and medical consultations. Multivariate logistic regression models were applied. Rates of abstinence between ND-only and both ND-MD and ND-SUMD differed in the 'intention-to-treat' sample, with the former group showing the best rate (62.5%, 48% and 45.4% respectively). ND-SUD had the second-best rate of abstinence (56.1%). Differences between groups were not observed among 'completers-only'. Self-report 7-day point prevalence abstinence is economical and reliable to be used in low to middle-income countries. In this study, it showed that the 6-week smoking cessation treatment had a positive effect among completers, which supports the importance of investing in treatment to decrease smoking prevalence in this population.
- Dissipating the fog: Cognitive trajectories and risk factors 1 year after COVID-19 hospitalization(2023) GONCALVES, Natalia Gomes; ALIBERTI, Marlon Juliano Romero; BERTOLA, Laiss; AVELINO-SILVA, Thiago; DIAS, Murilo Bacchini; APOLINARIO, Daniel; BUSATTO, Geraldo; FORLENZA, Orestes; NITRINI, Ricardo; BRUCKI, Sonia Maria Dozzi; BRUNONI, Andre Russowsky; VIDAL, Kallene Summer Moreira; JACOB-FILHO, Wilson; SUEMOTO, Claudia KimieIntroduction: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. Methods: A total of 1105 adults (mean age SD 64.9 9.9 years, 44% women, 63% White) with severe coronavirus disease 2019 (COVID-19) were evaluated for cognitive function 1 year after hospital discharge. Scores from cognitive tests were harmonized, and clusters of cognitive impairment were defined using sequential analysis. Results: Three groups of cognitive trajectories we re observed during the follow-up: no cognitive impairment, initial short-term cognitive impairment, and long-term cognitive impairment. Predictors of cognitive decline after COVID-19 were older age (beta = -0.013, 95% CI = -0.023;-0.003), female sex (beta = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (beta = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (beta = -0.191, 95% CI = -0.264;-0.119), higher platelet count (beta = -0.101, 95% CI = -0.185;-0.018), and delirium (beta = -0.483, 95% CI = -0.724;-0.244). Post-discharge predictors included hospital readmissions and frailty. Discussion: Cognitive impairment was common and the patterns of cognitive trajectories depended on sociodemographic, in-hospital, and post-hospitalization predictors. Highlights Cognitive impairment after coronavirus disease 2019 (COVID-19) hospital discharge was associated with higher age, less education, delirium during hospitalization, a higher number of hospitalizations post discharge, and frailty before and after hospitalization. Frequent cognitive evaluations for 12-month post-COVID-19 hospitalization showed three possible cognitive trajectories: no cognitive impairment, initial short-term impairment, and long-term impairment. This study highlights the importance of frequent cognitive testing to determine patterns of COVID-19 cognitive impairment, given the high frequency of incident cognitive impairment 1 year after hospitalization.
- Balance and Gait Associations With Cognitive Impairment and Dementia in Individuals With Down Syndrome(2023) CONCEICAO, Aline S. G. G.; SANT'ANA, Livea F. G.; MATTAR, Guilherme P.; SILVA, Maria de Fatima R.; RAMOS, Andressa R.; OLIVEIRA, Alexandra M.; CARVALHO, Claudia L.; GONCALVES, Octavio R.; VAROTTO, Bruna L. R.; MARTINEZ, Luana D.; LEDUC, Vinicius; FONSECA, Luciana M.; FORLENZA, Orestes V.Background: Atypical aging in Down syndrome (DS) is associated with neuropathological characteristics consistent with Alzheimer disease. Gait abnormalities have been shown to be associated with an increased risk of dementia for the general population. The aim of this study was to determine whether gait disorders are associated with worse cognitive performance and dementia in adults with DS.Methods: We evaluated 66 individuals with DS (>= 20 y of age), divided into 3 groups: stable cognition, prodromal dementia, and dementia (presumed Alzheimer disease). Each individual was evaluated with the Performance-Oriented Mobility Assessment (POMA), Timed Up and Go test, and Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS), in addition to a comprehensive clinical protocol to ascertain the occurrence of medical or psychiatric comorbidities.Results: The score on the POMA-Gait subscale score and body mass index were found to be independent predictors of prodromal dementia and dementia (P<0.001 for both). With the exception of perception, all cognitive domains correlated with the POMA-Total score (P<0.05).Conclusion: A lower POMA-Gait score increases the chance of prodromal dementia and dementia in adults with DS. Unlike other research, in this study higher body mass index was also found to increase the chance of prodromal dementia and dementia. In those individuals, applying the POMA could facilitate the early diagnosis of dementia, help identify fall risks, and promote the adoption of geriatric interventions focused on improving functional mobility.
- Self-reported bruxism in patients with post-traumatic stress disorder(2024) SOLIS, Ana Cristina de Oliveira; CORCHS, Felipe; DURAN, erica Panzani; SILVA, Claudio; REAL, Natalia Del; ARAUJO, alvaro Cabral; WANG, Yuan-Pang; LOTUFO-NETO, FranciscoObjective The present study aimed to investigate the association between self-reported awake/sleep bruxism, and orofacial pain with post-traumatic stress disorder (PTSD). Methods A case-control study with a convenience sample was designed. Participants were recruited from a university-based Trauma Ambulatory. The diagnosis of PTSD was established through a clinical interview and the Structured Clinical Interview (SCID-I/P). Thirty-eight PTSD patients and 38 controls completed the Research Diagnostic Criteria for Temporomandibular Disorders Axis-II to categorize awake/sleep bruxism and orofacial pain. Following this, we performed a short clinical examination of the temporomandibular joint and extraoral muscles. Results Adjusted logistic regression analysis showed that awake bruxism was associated with PTSD (OR = 3.38, 95% CI = 1.01-11.27, p = 0.047). Sleep bruxism was not associated with any covariate included in the model. In a Poisson regression model, PTSD (IRR = 3.01, 95% CI = 1.38-6.55, p = 0.005) and the muscle pain/discomfort (IRR = 5.12, 95% CI = 2.80-9.36, p < 0.001) were significant predictors for current orofacial pain. Conclusions PTSD was associated with self-reported awake bruxism and low-intensity orofacial pain. These conditions were frequent outcomes in patients previously exposed to traumatic events. Clinical relevance We suggest including a two-question screening for bruxism in psychiatry/psychology interviews to improve under-identification and to prevent harmful consequences at the orofacial level.
- Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes(2023) BORGES, Marina S.; HOFFMANN, Mauricio S.; SIMIONI, Andre; AXELRUD, Luiza K.; TEIXEIRA, Danielle S.; ZUGMAN, Andre; JACKOWSKI, Andrea; PAN, Pedro M.; BRESSAN, Rodrigo A.; PARKER, Nadine; GERMANN, Jurgen; BADO, Patricia P.; SATTERTHWAITE, Theodore D.; MILHAM, Michael P.; CHAKRAVARTY, M. Mallar; ROHDE, Luis Augusto Paim; MIGUEL, Euripedes Constantino; PAUS, Tomas; SALUM, Giovanni A.Background Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. Methods Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. Results Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. Conclusions Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.
- An Evaluation of Item Harmonization Strategies Between Assessment Tools of Psychopathology in Children and Adolescents(2024) HOFFMANN, Mauricio Scopel; MOORE, Tyler Maxwell; AXELRUD, Luiza Kvitko; TOTTENHAM, Nim; PAN, Pedro Mario; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; MILHAM, Michael Peter; SATTERTHWAITE, Theodore Daniel; SALUM, Giovanni AbrahaoData aggregation in mental health is complicated by using different questionnaires, and little is known about the impact of item harmonization strategies on measurement precision. Therefore, we aimed to assess the impact of various item harmonization strategies for a target and proxy questionnaire using correlated and bifactor models. Data were obtained from the Brazilian High-Risk Study for Mental Conditions (BHRCS) and the Healthy Brain Network (HBN; N = 6,140, ages 5-22 years, 39.6% females). We tested six item-wise harmonization strategies and compared them based on several indices. The one-by-one (1:1) expert-based semantic item harmonization presented the best strategy as it was the only that resulted in scalar-invariant models for both samples and factor models. The between-questionnaires factor correlation, reliability, and factor score difference in using a proxy instead of a target measure improved little when all other harmonization strategies were compared with a completely at-random strategy. However, for bifactor models, between-questionnaire specific factor correlation increased from 0.05-0.19 (random item harmonization) to 0.43-0.60 (expert-based 1:1 semantic harmonization) in BHRCS and HBN samples, respectively. Therefore, item harmonization strategies are relevant for specific factors from bifactor models and had little impact on p-factors and first-order correlated factors when the child behavior checklist (CBCL) and strengths and difficulties questionnaire (SDQ) were harmonized.
- Exploring the Acquisition of Social Communication Skills in Children with Autism: Preliminary Findings from Applied Behavior Analysis (ABA), Parent Training, and Video Modeling(2024) BORDINI, Daniela; MOYA, Ana Claudia; ASEVEDO, Graccielle Rodrigues da Cunha; PAULA, Cristiane Silvestre; BRUNONI, Decio; BRENTANI, Helena; CAETANO, Sheila Cavalcante; MARI, Jair de Jesus; BAGAIOLO, LeilaSocial communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings.
- Comparing mental health semi-structured diagnostic interviews and symptom checklists to predict poor life outcomes: an 8-yearcohort studyfrom childhoodtoyoung adulthood in Brazil(2024) HOFFMANN, Mauricio Scopel; PINE, Daniel S.; GEORGIADES, Katholiki; SZATMARI, Peter; MIGUEL, Euripedes Constantino; PAN, Pedro Mario; GADELHA, Ary; ROHDE, Luis Augusto; MERIKANGAS, Kathleen Ries; MILHAM, Michael Peter; SATTERTHWAITE, Theodore Daniel; SALUM, Giovanni AbrahaoBackground Semi-structured diagnos t i c interviews and symptom checkli s t s present similar internal relia b i l i t y . We a i m to investigate whether they differ in predicting poor life outcomes in the transition from childhood to young adulthood. Methods For this longitudinal st u d y , we used data from the Brazilian High Risk Cohort St u d y for Childhood Ment a Health Conditions. Eligible participants were a g e d 6-14 years on the day of study enrolment (January to February, 2010) and were enrolled in public schools by a biological parent in Porto Alegre and Sao Paulo, Brazil. 2511 young people and their caregivers were assessed at baseline in 2010-11, and 1917 were assessed 8 years later (2018-19; 76 center dot 3% retention). Clinical thresholds were derived using semi-structured parent-report interview based on the Diagnostic and Statistical Manual of Mental Disorders, according to the Developmental and Well-being Assessment (DAWBA), and clinical scores as defined by the Child Behavior Checklist (CBCL; T-score >= 70 considered positive caseness). At 8 years, participants were assessed for a composite life-threatening outcome (a composite of death, suicide attempts, severe self-harm, psychiatric inpatient admission, or emergency department visits) and a composite poor life chances outcome (a composite of any criminal conviction, substance misuse, or school dropout). We evaluated the accuracy of DAWBA and CBCL to predict these outcomes. Logistic regression models were adjusted for age, sex, race or ethnicity, st u d y site, and socioeconomic class. Findings DAWBA and CBCL had similar sensitivity, specificity , predictive values, and test accuracy for both composi t e outcomes and t h e i r components. Any mental health problem, as classified by DAWBA and CBCL, was independently associated with the composite life-threatening outcome (DAWBA adjusted odds ratio 1 center dot 62, 95% CI 1 center dot 20-2 center dot 18; CBCL 1 center dot 66, 1 center dot 19-2 center dot 30), but only CBCL independe n t l y predic t e d poor life chances (1 center dot 56, 1 center dot 19-2 center dot 04). Participants classified by b o t h approaches did not have higher odds of the life-threatening outcome when compared with participants classified by DAWBA or CBCL alone, nor for the poor life chances outcome when compared with those classified by CBCL alone. Interpretation Classifying children and adolescents based on a semi-structured diagnostic interview was not statistic a l l y different to symptom checklist in terms of test accuracy and predictive validity for relevant life outcomes. Classification based on symptom checklist might be a valid alternative to costly and time-consuming methods to identif y young peopl e a t risk f o r poor lif e outcomes.
- Essential data dimensions for prospective international data collection in older age bipolar disorder (OABD): Recommendations from the GAGE-BD group(2023) LAVIN, Paola; REJ, Soham; OLAGUNJU, Andrew T.; TEIXEIRA, Antonio L.; DOLS, Annemieke; ALDA, Martin; ALMEIDA, Osvaldo P.; ALTINBAS, Kursat; BALANZA-MARTINEZ, Vicent; BARBOSA, Izabela G.; BLUMBERG, Hilary P.; BRIGGS, Farren; CALKIN, Cynthia; CASSIDY, Kristin; FORESTER, Brent P.; FORLENZA, Orestes V.; HAJEK, Tomas; HAARMAN, Barthomeus C. M.; JIMENEZ, Esther; LAFER, Beny; MULSANT, Benoit; OLUWANIYI, Stephen O.; PATRICK, Regan; RADUA, Joaquim; SCHOUWS, Sigfried; SEKHON, Harmehr; SIMHANDL, Christian; SOARES, Jair C.; TSAI, Shang-Ying; VIETA, Eduard; VILLA, Luca M.; SAJATOVIC, Martha; EYLER, Lisa T.BackgroundBy 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged >= 50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients. MethodsWe developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n >= 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health. ResultsWe identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables. ConclusionThe essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD.
- Genomic loci influence patterns of structural covariance in the human brain(2023) WEN, Junhao; NASRALLAH, Ilya M.; ABDULKADIR, Ahmed; SATTERTHWAITE, Theodore D.; YANG, Zhijian; ERUS, Guray; ROBERT-FITZGERALD, Timothy; SINGH, Ashish; SOTIRAS, Aristeidis; BOQUET-PUJADAS, Aleix; MAMOURIAN, Elizabeth; DOSHI, Jimit; CUI, Yuhan; SRINIVASAN, Dhivya; SKAMPARDONI, Ioanna; CHEN, Jiong; HWANG, Gyujoon; BERGMAN, Mark; BAO, Jingxuan; VETURI, Yogasudha; ZHOU, Zhen; YANG, Shu; DAZZAN, Paola; KAHN, Rene S.; SCHNACK, Hugo G.; ZANETTI, Marcus V.; MEISENZAHL, Eva; BUSATTO, Geraldo F.; CRESPO-FACORRO, Benedicto; PANTELIS, Christos; WOOD, Stephen J.; ZHUO, Chuanjun; SHINOHARA, Russell T.; GUR, Ruben C.; GUR, Raquel E.; KOUTSOULERIS, Nikolaos; WOLF, Daniel H.; SAYKIN, Andrew J.; RITCHIE, Marylyn D.; SHEN, Li; THOMPSON, Paul M.; COLLIOT, Olivier; WITTFELD, Katharina; GRABE, Hans J.; TOSUN, Duygu; BILGEL, Murat; AN, Yang; MARCUS, Daniel S.; LAMONTAGNE, Pamela; HECKBERT, Susan R.; AUSTIN, Thomas R.; LAUNER, Lenore J.; ESPELAND, Mark; MASTERS, Colin L.; MARUFF, Paul; FRIPP, Jurgen; JOHNSON, Sterling C.; MORRIS, John C.; ALBERT, Marilyn S.; BRYAN, R. Nick; RESNICK, Susan M.; FAN, Yong; HABES, Mohamad; WOLK, David; SHOU, Haochang; DAVATZIKOS, ChristosNormal and pathologic neurobiological processes influence brain morphology in coordi-nated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these pat-terns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data- driven, multi -scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neuro-degeneration and dementia. Using support vector machines, multi -scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and bio-logical underpinnings that influence structural covariance patterns in the human brain.
- Examining the Gambling-Related Harms, Gambling Disorder, and Player Characteristics of Jogo do Bicho (an Illegal National Lottery) in a Representative Sample of Brazilian Lottery Players(2024) KIM, Hyoun S.; SANCHES, Marcos; MARIANI, Mirella Martins de Castro; HODGINS, David C.; TAVARES, HermanoWe investigated the demographics, gambling-related harms, and risk for gambling disorder (GD) associated with an illegal national lottery-type game called Jogo do Bicho that is culturally unique to Brazil in a sample of 5407 representative Brazilian lottery players. Participants reported on demographics, gambling behaviors, gambling-related harms, and GD. A total of 27.0% of the participants reported playing Jogo do Bicho in the past year. Jogo do Bicho was associated with greater risk of GD with 5.7% of current Jogo do Bicho players meeting diagnostic criteria. Jogo do Bicho was also associated with greater gambling-related harms. Older participants, males, individuals who self-identified as Black, and who were widowed were more likely to be current Jogo do Bicho players. Jogo do Bicho is a popular activity among legal lottery players in Brazil despite its illegal status and is associated with greater harms and increased risk of GD.
- Human archetypal pluripotent stem cells differentiate into trophoblast stem cells via endogenous BMP5/7 induction without transitioning through naive state(2024) TIETZE, Ethan; BARBOSA, Andre Rocha; ARAUJO, Bruno; EUCLYDES, Veronica; SPIEGELBERG, Bailey; CHO, Hyeon Jin; LEE, Yong Kyu; WANG, Yanhong; MCCORD, Alejandra; LORENZETTI, Alan; FELTRIN, Arthur; LEEMPUT, Joyce van de; CARLO, Pasquale Di; URSINI, Gianluca; BENJAMIN, Kynon J.; BRENTANI, Helena; KLEINMAN, Joel E.; HYDE, Thomas M.; WEINBERGER, Daniel R.; MCKAY, Ronald; SHIN, Joo Heon; SAWADA, Tomoyo; PAQUOLA, Apua C. M.; ERWIN, Jennifer A.Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGF beta), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)-a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.
- Attention-deficit/hyperactivity disorder(2024) FARAONE, Stephen V.; BELLGROVE, Mark A.; BRIKELL, Isabell; CORTESE, Samuele; HARTMAN, Catharina A.; HOLLIS, Chris; NEWCORN, Jeffrey H.; PHILIPSEN, Alexandra; POLANCZYK, Guilherme V.; RUBIA, Katya; SIBLEY, Margaret H.; BUITELAAR, Jan K.Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been difficult to establish. The heterogeneity of the condition is evident in the diverse presentation of symptoms and levels of impairment, the numerous co-occurring mental and physical conditions, the various domains of neurocognitive impairment, and extensive minor structural and functional brain differences. The diagnosis of ADHD is reliable and valid when evaluated with standard diagnostic criteria. Curative treatments for ADHD do not exist but evidence-based treatments substantially reduce symptoms and/or functional impairment. Medications are effective for core symptoms and are usually well tolerated. Some non-pharmacological treatments are valuable, especially for improving adaptive functioning. Clinical and neurobiological research is ongoing and could lead to the creation of personalized diagnostic and therapeutic approaches for this disorder. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that typically starts in childhood. This Primer summarizes the epidemiology, mechanisms, diagnosis and treatment of ADHD.
- Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project(2024) SAJATOVIC, Martha; REJ, Soham; ALMEIDA, Osvaldo P.; ALTINBAS, Kursat; BALANZA-MARTINEZ, Vicent; BARBOSA, Izabela G.; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; BRIGGS, Farren B. S.; DOLS, Annemiek; FORESTER, Brent P.; FORLENZA, Orestes V.; GILDENGERS, Ariel G.; JIMENEZ, Esther; KLAUS, Federica; LAFER, Beny; MULSANT, Benoit; MWANGI, Benson; NUNES, Paula Villela; OLAGUNJU, Andrew T.; OLUWANIYI, Stephen; ORHAN, Melis; PATRICK, Regan E.; RADUA, Joaquim; RAJJI, Tarek; SARNA, Kaylee; SCHOUWS, Sigfried; SIMHANDL, Christian; SEKHON, Harmehr; SOARES, Jair C.; SUTHERLAND, Ashley N.; TEIXEIRA, Antonio L.; TSAI, Shangying; VIDAL-RUBIO, Sonia; VIETA, Eduard; YALA, Joy; EYLER, Lisa T.Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean +/- standard deviation age 47.2 +/- 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p <= 0.001, depression p <= 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.
- BDNF rs6265 differentially influences neurometabolites in the anterior cingulate of healthy and bipolar disorder subjects(2023) SCOTTI-MUZZI, Estevao; CHILE, Thais; VALLADA, Homero; OTADUY, Maria Concepcion Garcia; SOEIRO-DE-SOUZA, Marcio GerhardtBrain-derived neurotrophic factor (BDNF) is the most abundant brain neurotrophin and plays a critical role in neuronal growth, survival and plasticity, implicated in the pathophysiology of Bipolar Disorders (BD). The single-nucleotide polymorphism in the BDNF gene (BDNF rs6265) has been associated with decreased hippocampal BDNF secretion and volume in met carriers in different populations, although the val allele has been reported to be more frequent in BD patients. The anterior cingulate cortex (ACC) is a key center integrating cognitive and affective neuronal connections, where consistent alterations in brain metabolites such as Glx (Glutamate + Glutamine) and N-acetylaspartate (NAA) have been consistently reported in BD. However, little is known about the influence of BDNF rs6265 on neurochemical profile in the ACC of Healthy Controls (HC) and BD subjects. The aim of this study was to assess the influence of BDNF rs6265 on ACC neurometabolites (Glx, NAA and total creatine- Cr) in 124 euthymic BD type I patients and 76 HC, who were genotyped for BDNF rs6265 and underwent a 3-Tesla proton magnetic resonance imaging and spectroscopy scan ((1) H-MRS) using a PRESS ACC single-voxel (8cm(3)) sequence. BDNF rs6265 polymorphism showed a significant two-way interaction (diagnosis x genotype) in relation to NAA/Cr and total Cr. While met carriers presented increased NAA/Cr in HC, BD-I subjects with the val allele revealed higher total Cr, denoting an enhanced ACC metabolism likely associated with increased glutamatergic metabolites observed in BD-I val carriers. However, these results were replicated only in men. Therefore, our results support evidences that the BDNF rs6265 polymorphism exerts a complex pleiotropic effect on ACC metabolites influenced by the diagnosis and sex.
- An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels(2023) LEON, J. de; SCHORETSANITIS, G.; SMITH, R. L.; MOLDEN, E.; SOLISMAA, A.; SEPPäLä, N.; KOPEčEK, M.; ŠVANCER, P.; OLMOS, I.; RICCIARDI, C.; IGLESIAS-GARCIA, C.; ORTIZ, B. B.; ELKIS, H.; PALHA, A. J. Pacheco; LLERENA, A.; FERNANDEZ-EGEA, E.; SISKIND, D.; WEIZMAN, A.; MASMOUDI, R.; SAFFIAN, S. Mohd; LEUNG, J. G.; BUCKLEY, P. F.; MARDER, S. R.; CITROME, L.; FREUDENREICH, O.; CORRELL, C. U.; MüLLER, D. J.; IGLESIAS-ALONSO, A.; SPINA, E.; RUAN, C.-J.; WANG, C.-Y.; WANG, G.; TANG, Y.-L.; LIN, S.-K.; LANE, H.-Y.; KIM, Y. S.; KIM, S. H.; RAJKUMAR, A. P.; GONZáLEZ-ESQUIVEL, D. F.; JUNG-COOK, H.; BAPTISTA, T.; ROHDE, C.; NIELSEN, J.; VERDOUX, H.; QUILES, C.; SANZ, E. J.; CUEVAS, C. De las; COHEN, D.; SCHULTE, P. F. J.; ERTUğRUL, A.; YAğCıOğLU, A. E. Anıl; CHOPRA, N.; MCCOLLUM, B.; SHELTON, C.; COTES, R. O.; KAITHI, A. R.; KANE, J. M.; FAROOQ, S.; NG, C. H.; BILBILY, J.; HIEMKE, C.; LóPEZ-JARAMILLO, C.; MCGRANE, I.; LANA, F.; EAP, C. B.; ARROJO-ROMERO, M.; RăDULESCU, F.Ş.; SEIFRITZ, E.; EVERY-PALMER, S.; BOUSMAN, C. A.; BEBAWI, E.; BHATTACHARYA, R.; KELLY, D. L.; OTSUKA, Y.; LAZARY, J.; TORRES, R.; YECORA, A.; MOTUCA, M.; CHAN, S. K. W.; ZOLEZZI, M.; OUANES, S.; BERARDIS, D. De; GROVER, S.; PROCYSHYN, R. M.; ADEBAYO, R. A.; KIRILOCHEV, O. O.; SOLOVIEV, A.; FOUNTOULAKIS, K. N.; WILKOWSKA, A.; CUBAłA, W. J.; AYUB, M.; SILVA, A.; BONELLI, R. M.; VILLAGRáN-MORENO, J. M.; CRESPO-FACORRO, B.; TEMMINGH, H.; DECLOEDT, E.; PEDRO, M. R.; TAKEUCHI, H.; TSUKAHARA, M.; GRüNDER, G.; SAGUD, M.; CELOFIGA, A.; RISTIC, D. IgnjatovicThis is the Spanish translation of an international guideline which proposes improving clozapine package inserts worldwide by using ancestry-based: 1) dosing and 2) titration. Adverse drug reaction (ADR) databases suggest clozapine: 1) is the third most toxic drug in the United States (US), and 2) produces worldwide pneumonia mortality four times greater than that of agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers require the lowest dose and male smokers the highest dose). Poor metabolizer (PM) status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity or inflammation with C-reactive protein (CRP) elevations. People with ancestry from Asia (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/ml. Daily doses of 300-600 mg/day are recommended in the US. Slow personalized titration may prevent early ADRs (including syncope, myocarditis and pneumonia). The core of this guideline consists of six personalized titration schedules for inpatients: 1) Asian/Amerindian ancestry with lower metabolism (in cases of obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) Asian/Amerindian ancestry with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (in cases of obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US of non-Asian/Amerindian ancestry with lower clozapine metabolism (in cases of obesity or valproate) needing 150-300 mg/day, and 6) in the US of non-Asian/Amerindian ancestry with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least 4 weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.