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1.
Proc Natl Acad Sci U S A ; 120(23): e2215572120, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252958

RESUMO

Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.

2.
Mol Psychiatry ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914807

RESUMO

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

3.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35135884

RESUMO

Mitochondrial inner NEET (MiNT) and the outer mitochondrial membrane (OMM) mitoNEET (mNT) proteins belong to the NEET protein family. This family plays a key role in mitochondrial labile iron and reactive oxygen species (ROS) homeostasis. NEET proteins contain labile [2Fe-2S] clusters which can be transferred to apo-acceptor proteins. In eukaryotes, the biogenesis of [2Fe-2S] clusters occurs within the mitochondria by the iron-sulfur cluster (ISC) system; the clusters are then transferred to [2Fe-2S] proteins within the mitochondria or exported to cytosolic proteins and the cytosolic iron-sulfur cluster assembly (CIA) system. The last step of export of the [2Fe-2S] is not yet fully characterized. Here we show that MiNT interacts with voltage-dependent anion channel 1 (VDAC1), a major OMM protein that connects the intermembrane space with the cytosol and participates in regulating the levels of different ions including mitochondrial labile iron (mLI). We further show that VDAC1 is mediating the interaction between MiNT and mNT, in which MiNT transfers its [2Fe-2S] clusters from inside the mitochondria to mNT that is facing the cytosol. This MiNT-VDAC1-mNT interaction is shown both experimentally and by computational calculations. Additionally, we show that modifying MiNT expression in breast cancer cells affects the dynamics of mitochondrial structure and morphology, mitochondrial function, and breast cancer tumor growth. Our findings reveal a pathway for the transfer of [2Fe-2S] clusters, which are assembled inside the mitochondria, to the cytosol.


Assuntos
Citosol/metabolismo , Compostos Ferrosos/metabolismo , Mitocôndrias/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Simulação por Computador , Matriz Extracelular , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Glicólise , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Neoplasias Experimentais , Consumo de Oxigênio , Canal de Ânion 1 Dependente de Voltagem/genética
4.
Br J Psychiatry ; : 1-3, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320844

RESUMO

In our ever digitalising society, our engagement with the online world has significant potential to have a negative impact on our mental health. Although the roles of public health and psychiatry are debated, clinicians are in a strategic position to assess usage and intervene, to prevent harms from problematic engagement with the internet.

5.
J Pathol ; 259(1): 10-20, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36210634

RESUMO

Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre-replicative complex, is essential for loading the minichromosome maintenance complex (MCM) helicases onto the origins of DNA replication. While several studies have shown that dysregulation of CDT1 expression causes re-replication and DNA damage in cell lines, and CDT1 is highly expressed in several human cancers, whether CDT1 deregulation is sufficient to enhance tumorigenesis in vivo is currently unclear. To delineate its role in vivo, we overexpressed Cdt1 in the mouse colon and induced carcinogenesis using azoxymethane/dextran sodium sulfate (AOM/DSS). Here, we show that mice overexpressing Cdt1 develop a significantly higher number of tumors with increased tumor size, and more severe dysplastic changes (high-grade dysplasia), compared with control mice under the same treatment. These tumors exhibited an increased growth rate, while cells overexpressing Cdt1 loaded greater amounts of Mcm2 onto chromatin, demonstrating origin overlicensing. Adenomas overexpressing Cdt1 showed activation of the DNA damage response (DDR), apoptosis, formation of micronuclei, and chromosome segregation errors, indicating that aberrant expression of Cdt1 results in increased genomic and chromosomal instability in vivo, favoring cancer development. In line with these results, high-level expression of CDT1 in human colorectal cancer tissue specimens and colorectal cancer cell lines correlated significantly with increased origin licensing, activation of the DDR, and microsatellite instability (MSI). © 2022 The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias Colorretais , Replicação do DNA , Proteínas de Ligação a DNA , Animais , Humanos , Camundongos , Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Dano ao DNA , Proteínas de Ligação a DNA/metabolismo
6.
CNS Spectr ; 29(4): 273-278, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38757162

RESUMO

OBJECTIVES: Gambling disorder affects 0.5-2.4% of the population and shows strong associations with lifetime alcohol use disorder. Very little is known regarding whether lifetime alcohol use disorder can impact the clinical presentation or outcome trajectory of gambling disorder. METHODS: Data were pooled from previous clinical trials conducted on people with gambling disorder, none of whom had current alcohol use disorder. Demographic and clinical variables were compared between those who did versus did not have lifetime alcohol use disorder. RESULTS: Of the 621 participants in the clinical trials, 103 (16.6%) had a lifetime history of alcohol use disorder. History of alcohol use disorder was significantly associated with male gender (relative risk [RR] = 1.42), greater body weight (Cohen's D = 0.27), family history of alcohol use disorder in first-degree relative(s) (RR = 1.46), occurrence of previous hospitalization due to psychiatric illness (RR = 2.68), and higher gambling-related legal problems (RR = 1.50). History of alcohol use disorder was not significantly associated with other variables that were examined, such as severity of gambling disorder or extent of functional disability. Lifetime alcohol use disorder was not significantly associated with the extent of clinical improvement in gambling disorder symptoms during the subsequent clinical trials. CONCLUSIONS: These data highlight that lifetime alcohol use disorder is an important clinical variable to be considered when assessing gambling disorder because it is associated with several untoward features (especially gambling-related legal problems and prior psychiatric hospitalization). The study design enabled these associations to be disambiguated from current or recent alcohol use disorder.


Assuntos
Jogo de Azar , Humanos , Jogo de Azar/terapia , Jogo de Azar/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Alcoolismo/epidemiologia , Resultado do Tratamento
7.
CNS Spectr ; 29(3): 158-165, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477170

RESUMO

OBJECTIVE: Trichotillomania (TTM) is a mental health disorder characterized by repetitive urges to pull out one's hair. Cognitive deficits have been reported in people with TTM compared to controls; however, the current literature is sparse and inconclusive about affected domains. We aimed to synthesize research on cognitive functioning in TTM and investigate which cognitive domains are impaired. METHODS: After preregistration on the International Prospective Register of Systematic Reviews (PROSPERO), we conducted a comprehensive literature search for papers examining cognition in people with TTM versus controls using validated tests. A total of 793 papers were screened using preestablished inclusion/exclusion criteria, yielding 15 eligible studies. Random-effects meta-analysis was conducted for 12 cognitive domains. RESULTS: Meta-analysis demonstrated significant deficits in motor inhibition and extradimensional (ED) shifting in people with TTM versus controls as measured by the stop-signal task (SST) (Hedge's g = 0.45, [CI: 0.14, 0.75], p = .004) and ED set-shift task (g = 0.38, [CI: 0.13, 0.62], p = .003), respectively. There were no significant between-group differences in the other cognitive domains tested: verbal learning, intradimensional (ID) shifting, road map spatial ability, pattern recognition, nonverbal memory, executive planning, spatial span length, Stroop inhibition, Wisconsin card sorting, and visuospatial functioning. Findings were not significantly moderated by study quality scores. CONCLUSIONS: Motor inhibition and ED set-shifting appear impaired in TTM. However, a cautious interpretation of results is necessary as samples were relatively small and frequently included comorbidities. Treatment interventions seeking to improve inhibitory control and cognitive flexibility merit exploration for TTM.


Assuntos
Tricotilomania , Humanos , Cognição , Testes Neuropsicológicos , Tricotilomania/psicologia , Tricotilomania/epidemiologia
8.
CNS Spectr ; 29(3): 166-175, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38487834

RESUMO

OBJECTIVE: The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies. METHODS: The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria. RESULTS: Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val-Val participants). There were insufficient nature and number of studies for meta-analysis. CONCLUSION: The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).


Assuntos
Inibidores de Catecol O-Metiltransferase , Catecol O-Metiltransferase , Cognição , Tolcapona , Humanos , Inibidores de Catecol O-Metiltransferase/farmacologia , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Cognição/efeitos dos fármacos , Catecol O-Metiltransferase/genética , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Adulto , Memória de Curto Prazo/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Compr Psychiatry ; 127: 152429, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37832377

RESUMO

Compulsivity is a transdiagnostic construct crucial to understanding multiple psychiatric conditions and problematic repetitive behaviours. Despite being identified as a clinical- and research-relevant construct, there are limited insights into the internal conceptual structure of compulsivity. To provide a more nuanced understanding of compulsivity, the current study estimated the structure of compulsivity (indexed using the previously validated Cambridge-Chicago Compulsivity Trait Scale, CHI-T) among two large-scale and geographically distinct samples using the network estimation method. The samples consisted of a United Kingdom cohort (n = 122,346, 51.4% female, Mean age = 43.7, SD = 16.5, range = 9-86 years) and a South Africa cohort (n = 2674, 65.6% female, Mean age = 24.6, SD = 8.6, range = 18-65 years). Network community analysis demonstrated that compulsivity was constituted of three interrelated dimensions, namely: perfectionism, cognitive rigidity and reward drive. Further, 'Completion leads to soothing' and 'Difficulty moving from task to task' were identified as core (central nodes) to compulsivity. The dimensional structure and central nodes of compulsivity networks were consistent across the two samples. These findings facilitate the conceptualisation and measurement of compulsivity and may contribute to the early detection and treatment of compulsivity-related disorders.


Assuntos
Comportamento Compulsivo , Comportamento Impulsivo , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Comportamento Compulsivo/diagnóstico , Comportamento Compulsivo/psicologia , Transtorno da Personalidade Compulsiva , Recompensa , Fenótipo
10.
Compr Psychiatry ; 122: 152366, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36702061

RESUMO

BACKGROUND: Problematic usage of the internet (PUI) is an umbrella term, referring to a variety of maladaptive online behaviors linked to functional impairment. There is ongoing need for the development of instruments capturing not only PUI severity, but also the online activity types. The Internet Severity and Activities Questionnaire (ISAAQ), previously developed to address this need, required further refinement and validation. METHODS: Cross-sectional data was gathered in two separate samples (South Africa n = 3275, USA-UK n = 943) using the Internet Severity and Activities Addiction Questionnaire (ISAAQ). Item Response Theory (IRT) was used to examine the properties of the scale (Part A of the ISAAQ) and differential item functioning against demographic parameters. The severity scale of the ISAAQ was optimized by eliminating the poorest performing items using an iterative approach and examining validity metrics. Cluster analyses was used to examine internet activities and commonalities across samples (Part B of the ISAAQ). RESULTS: Optimization of ISAAQ using IRT yielded a refined 10-item version (ISAAQ-10), with less differential item functioning and a robust unidimensional factor structure. The ISAAQ-10 severity score correlated strongly with established measures of internet addiction (Compulsive Internet Use Scale [Person's r = 0.86] and the Internet Addiction Test-10 [r = 0.75]). Combined with gaming activity score it correlated moderately strongly with the established Internet Gaming Disorder Test (r = 0.65). Exploratory cluster analyses in both samples identified two groups, one of "low-PUI" [98.1-98.5%], and one of "high-PUI" [1.5-1.9%]. Multiple facets of internet activity appeared elevated in the high-PUI cluster. DISCUSSION: The ISAAQ-10 supersedes the earlier longer version of the ISAAQ, and provides a useful, psychometrically robust measure of PUI severity (Part A), and captures the extent of engagement in a wide gamut of online specific internet activities (Part B). ISAAQ-10 constitutes a valuable objective measurement tool for future studies.


Assuntos
Comportamento Aditivo , Transtorno de Adição à Internet , Humanos , Psicometria/métodos , Estudos Transversais , Inquéritos e Questionários , Análise por Conglomerados , Internet , Reprodutibilidade dos Testes
11.
Compr Psychiatry ; 122: 152378, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36801816

RESUMO

Problematic usage of the internet (PUI) is of increasing concern in a digitalized world. While several screening tools have been developed to assess PUI, few have had their psychometric properties evaluated, and existing scales are also not typically designed to quantify both the severity of PUI and the nature of diverse problematic online activities. The Internet Severity and Activities Addiction Questionnaire (ISAAQ), consisting of a severity scale (ISAAQ Part A) and an online activities scale (ISAAQ part B) was previously developed to address these limitations. This study undertook psychometric validation of ISAAQ Part A using data from three countries. The optimal one-factor structure of ISAAQ Part A was determined in a large dataset from South Africa, then validated against datasets from the United Kingdom and United States. The scale had high Cronbach's alpha (≥0.9 in each country). A working operational cut-off point was determined to distinguish between those with some degree of problematic use and those without (ISAAQ Part A), and insight was given into the types of potentially problematic activities that may encompass PUI (ISAAQ Part B).


Assuntos
Comportamento Aditivo , Humanos , Comportamento Aditivo/diagnóstico , Inquéritos e Questionários , Psicometria , Reino Unido , África do Sul , Internet , Reprodutibilidade dos Testes
12.
Compr Psychiatry ; 115: 152304, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35306448

RESUMO

BACKGROUND: There is growing concern about how people with eating disorders are impacted by the widespread societal restructuring during the COVID-19 crisis. AIMS: We aimed to examine how factors relating to the impact of the pandemic associate with eating disorders and quantify this relationship while adjusting for concurrent and longitudinal parameters of risk. METHODS: We gathered demographic, behavioral and clinical data pre- and mid-pandemic as well as childhood trauma history from a longitudinal online survey of 489 adults (mean age 23.4 years) recruited from the Neuroscience in Psychiatry Network (NSPN). Using pre-pandemic (T1) and concurrent (T2) data we aimed to predict eating disorders at mid-pandemic (T2). We deployed hierarchical generalized logistic regression to ascertain the strength of longitudinal and concurrent associations. RESULTS: Pre-pandemic eating disorder scores strongly associated with concurrent eating disorder (z = 5.93). More conflict at home mid-pandemic (z = 2.03), pre- (lower sensation seeking z = -2.58) and mid-pandemic (higher lack of perseverance z = 2.33) impulsivity traits also associated with mid-pandemic eating disorder. CONCLUSION: Conflict at home mid-pandemic and specific aspects of impulsiveness significantly associated with concurrent eating disorder when adjusted for pre-pandemic eating disorder symptoms, baseline demographics, behavioral traits, history of traumatic experiences and concurrent psychopathology. These results provide insight into the struggles of those suffering with eating disorders during the COVID-19 pandemic and highlight the importance of impulsiveness traits and the immediate family environment in their experience of illness during the pandemic.


Assuntos
Anorexia Nervosa , COVID-19 , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , COVID-19/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Humanos , Estudos Longitudinais , Pandemias , Reino Unido/epidemiologia , Adulto Jovem
13.
Compr Psychiatry ; 118: 152346, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36029549

RESUMO

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion. A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives. However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.


Assuntos
Comportamento Aditivo , COVID-19 , Jogo de Azar , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/epidemiologia , COVID-19/epidemiologia , Feminino , Jogo de Azar/epidemiologia , Humanos , Internet , Masculino , Pandemias
14.
Curr Psychiatry Rep ; 23(9): 56, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264408

RESUMO

PURPOSE OF REVIEW: We aimed to accrue recent evidence exploring effects of modern online activities (e.g., Internet use) on feeding and eating disorder symptoms, and related traits. We examined available evidence to ascertain any direct influences from online activities on feeding and eating disorders, thereby shedding light on putative mechanisms by which those influences may occur. RECENT FINDINGS: Many facets of problematic usage of the Internet correlate cross sectionally with eating disorder and related psychopathology. There is evidence to suggest that significant effects do exist in the direction of specific Internet activities contributing to eating disorder symptoms, viewed dimensionally. Putative mechanisms are discussed. However, a significant number of eating disorder phenotypes and Internet-related activities remain under-researched. Specific facets of engagement with the online environment appear to confer risk for feeding and eating problems, evidence being strongest for non-clinical studies using dimensional measures. More research is required to rigorously confirm causal effects, including in patients meeting formal diagnostic criteria for eating disorders. We also highlight the need for high-quality evidence to explore how eating disorder phenotypes are commonly as well as uniquely affected by different online activities. Such research is needed in order that scientific understanding in this area can be translated to protect those most at risk of disordered eating, including through changes in public health approaches and clinical practice.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Psicopatologia
15.
BMC Med ; 18(1): 202, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32590978

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

16.
BMC Med ; 18(1): 32, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32050974

RESUMO

BACKGROUND: Childhood maltreatment has been associated with significant impairment in social, emotional and behavioural functioning later in life. Nevertheless, some individuals who have experienced childhood maltreatment function better than expected given their circumstances. MAIN BODY: Here, we provide an integrated understanding of the complex, interrelated mechanisms that facilitate such individual resilient functioning after childhood maltreatment. We aim to show that resilient functioning is not facilitated by any single 'resilience biomarker'. Rather, resilient functioning after childhood maltreatment is a product of complex processes and influences across multiple levels, ranging from 'bottom-up' polygenetic influences, to 'top-down' supportive social influences. We highlight the complex nature of resilient functioning and suggest how future studies could embrace a complexity theory approach and investigate multiple levels of biological organisation and their temporal dynamics in a longitudinal or prospective manner. This would involve using methods and tools that allow the characterisation of resilient functioning trajectories, attractor states and multidimensional/multilevel assessments of functioning. Such an approach necessitates large, longitudinal studies on the neurobiological mechanisms of resilient functioning after childhood maltreatment that cut across and integrate multiple levels of explanation (i.e. genetics, endocrine and immune systems, brain structure and function, cognition and environmental factors) and their temporal interconnections. CONCLUSION: We conclude that a turn towards complexity is likely to foster collaboration and integration across fields. It is a promising avenue which may guide future studies aimed to promote resilience in those who have experienced childhood maltreatment.


Assuntos
Encéfalo/fisiopatologia , Maus-Tratos Infantis/psicologia , Neurobiologia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino
17.
CNS Spectr ; 25(3): 409-418, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31159911

RESUMO

OBJECTIVE: Problematic internet users suffer from impairment in a variety of cognitive domains. Research suggests that COMT haplotypes exert differential effects on cognition. We sought to investigate differences in the genetic profiles of problematic internet users and whether those could shed light on potential cognitive differences. METHODS: We recruited 206 non-treatment seeking participants with heightened impulsive traits and obtained cross-sectional demographic, clinical, and cognitive data as well as the genetic haplotypes of COMT rs4680 and rs4818. We identified 24 participants who presented with problematic internet use (PIU) and compared PIU and non-PIU participants using one-way analysis of variance (ANOVA) and chi square as appropriate. RESULTS: PIU was associated with worse performance on decision making, rapid visual processing, and spatial working memory tasks. Genetic variants were associated with altered cognitive performance, but rates of PIU did not statistically differ for particular haplotypes of COMT. CONCLUSION: This study indicates that PIU is characterized by deficits in decision making and working memory domains; it also provides evidence for elevated impulsive responses and impaired target detection on a sustained attention task, which is a novel area worth exploring further in future work. The effects observed in the genetic influences on cognition of PIU subjects imply that the genetic heritable components of PIU may not lie within the genetic loci influencing COMT function and cognitive performance; or that the genetic component in PIU involves many genetic polymorphisms each conferring only a small effect.


Assuntos
Catecol O-Metiltransferase/genética , Transtorno de Adição à Internet/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Cognição , Tomada de Decisões , Feminino , Haplótipos , Humanos , Masculino
18.
Eur Eat Disord Rev ; 28(5): 551-558, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542781

RESUMO

OBJECTIVE: We aimed to evaluate the validity of a MARSIPAN-guidance-adapted Early Warning System (MARSI MEWS) and compare it to the National Early Warning Score (NEWS) and an adapted version of the Physical Risk in Eating Disorders Index (PREDIX), to ascertain whether current practice is comparable to best-practice standards. METHODS: We collated 3,937 observations from 36 inpatients from Addenbrookes Hospital over 2017-2018 and used three independent raters to create a "gold standard" of deteriorating cases. We ascertained performance metrics (Receiver Operating Characteristic Area Under the curve) for MARSI MEWS, NEWS and PREDIX; we also tested the proof of concept of a machine-learning-based early-warning-system (ML-EWS) using cross-validation and out-of-sample prediction of cases. RESULTS: The MARSI MEWS system showed higher ROC AUC (0.916) compared to NEWS (0.828) or PREDIX (0.865). ML-EWS (random forest) performed well at independent samples analysis (0.980) and multilevel analysis (0.922). CONCLUSION: MARSI MEWS seems most suitable for identifying critically deteriorating cases in anorexia nervosa inpatient population. We did not examine community practice in which the PREDIX arguably remains the best to ascertain deteriorating cases. Our results also provide a first proof of concept for the development of artificial-intelligence-based early warning systems in anorexia nervosa. Implications for inpatient clinical practice in eating disorders are discussed.


Assuntos
Anorexia Nervosa/terapia , Deterioração Clínica , Diagnóstico Precoce , Hospitalização , Monitorização Fisiológica/métodos , Adulto , Área Sob a Curva , Escore de Alerta Precoce , Feminino , Humanos , Masculino , Curva ROC , Reprodutibilidade dos Testes
19.
Br J Psychiatry ; 215(5): 639-646, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30784392

RESUMO

BACKGROUND: Excessive use of the internet is increasingly recognised as a global public health concern. Individual studies have reported cognitive impairment in problematic internet use (PIU), but have suffered from various methodological limitations. Confirmation of cognitive deficits in PIU would support the neurobiological plausibility of this disorder. AIMS: To conduct a rigorous meta-analysis of cognitive performance in PIU from case-control studies; and to assess the impact of study quality, the main type of online behaviour (for example gaming) and other parameters on the findings. METHOD: A systematic literature review was conducted of peer-reviewed case-controlled studies comparing cognition in people with PIU (broadly defined) with that of healthy controls. Findings were extracted and subjected to a meta-analysis where at least four publications existed for a given cognitive domain of interest. RESULTS: The meta-analysis comprised 2922 participants across 40 studies. Compared with controls, PIU was associated with significant impairment in inhibitory control (Stroop task Hedge's g = 0.53 (s.e. = 0.19-0.87), stop-signal task g = 0.42 (s.e. = 0.17-0.66), go/no-go task g = 0.51 (s.e. = 0.26-0.75)), decision-making (g = 0.49 (s.e. = 0.28-0.70)) and working memory (g = 0.40 (s.e. = 0.20-0.82)). Whether or not gaming was the predominant type of online behaviour did not significantly moderate the observed cognitive effects; nor did age, gender, geographical area of reporting or the presence of comorbidities. CONCLUSIONS: PIU is associated with decrements across a range of neuropsychological domains, irrespective of geographical location, supporting its cross-cultural and biological validity. These findings also suggest a common neurobiological vulnerability across PIU behaviours, including gaming, rather than a dissimilar neurocognitive profile for internet gaming disorder. DECLARATION OF INTEREST: S.R.C. consults for Cambridge Cognition and Shire. K.I.'s research activities were supported by Health Education East of England Higher Training Special interest sessions. A.E.G.'s research has been funded by Innovational grant (VIDI-scheme) from ZonMW: (91713354). N.A.F. has received research support from Lundbeck, Glaxo-SmithKline, European College of Neuropsychopharmacology (ECNP), Servier, Cephalon, Astra Zeneca, Medical Research Council (UK), National Institute for Health Research, Wellcome Foundation, University of Hertfordshire, EU (FP7) and Shire. N.A.F. has received honoraria for lectures at scientific meetings from Abbott, Otsuka, Lundbeck, Servier, Astra Zeneca, Jazz pharmaceuticals, Bristol Myers Squibb, UK College of Mental Health Pharmacists and British Association for Psychopharmacology (BAP). N.A.F. has received financial support to attend scientific meetings from RANZCP, Shire, Janssen, Lundbeck, Servier, Novartis, Bristol Myers Squibb, Cephalon, International College of Obsessive-Compulsive Spectrum Disorders, International Society for Behavioral Addiction, CINP, IFMAD, ECNP, BAP, the World Health Organization and the Royal College of Psychiatrists. N.A.F. has received financial royalties for publications from Oxford University Press and payment for editorial duties from Taylor and Francis. J.E.G. reports grants from the National Center for Responsible Gaming, Forest Pharmaceuticals, Takeda, Brainsway, and Roche and others from Oxford Press, Norton, McGraw-Hill and American Psychiatric Publishing outside of the submitted work.


Assuntos
Comportamento Aditivo , Transtornos Cognitivos , Disfunção Cognitiva , Comportamento Aditivo/epidemiologia , Cognição , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/epidemiologia , Inglaterra , Humanos , Internet , Uso da Internet
20.
BMC Psychiatry ; 19(1): 348, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703666

RESUMO

BACKGROUND: Problematic use of the Internet has been highlighted as needing further study by international bodies, including the European Union and American Psychiatric Association. Knowledge regarding the optimal classification of problematic use of the Internet, subtypes, and associations with clinical disorders has been hindered by reliance on measurement instruments characterized by limited psychometric properties and external validation. METHODS: Non-treatment seeking individuals were recruited from the community of Stellenbosch, South Africa (N = 1661), and Chicago, United States of America (N = 827). Participants completed an online version of the Internet Addiction Test, a widely used measure of problematic use of the Internet consisting of 20-items, measured on a 5-point Likert-scale. The online questions also included demographic measures, time spent engaging in different online activities, and clinical scales. The psychometric properties of the Internet Addiction Test, and potential problematic use of the Internet subtypes, were characterized using factor analysis and latent class analysis. RESULTS: Internet Addiction Test data were optimally conceptualized as unidimensional. Latent class analysis identified two groups: those essentially free from Internet use problems, and those with problematic use of the Internet situated along a unidimensional spectrum. Internet Addiction Test scores clearly differentiated these groups, but with different optimal cut-offs at each site. In the larger Stellenbosch dataset, there was evidence for two subtypes of problematic use of the Internet that differed in severity: a lower severity "impulsive" subtype (linked with attention-deficit hyperactivity disorder), and a higher severity "compulsive" subtype (linked with obsessive-compulsive personality traits). CONCLUSIONS: Problematic use of the Internet as measured by the Internet Addiction Test reflects a quasi-trait - a unipolar dimension in which most variance is restricted to a subset of people with problems regulating Internet use. There was no evidence for subtypes based on the type of online activities engaged in, which increased similarly with overall severity of Internet use problems. Measures of comorbid psychiatric symptoms, along with impulsivity, and compulsivity, appear valuable for differentiating clinical subtypes and could be included in the development of new instruments for assessing the presence and severity of Internet use problems.


Assuntos
Comportamento Aditivo/psicologia , Comportamento Compulsivo/psicologia , Comportamento Impulsivo , Internet , Adolescente , Adulto , Comorbidade , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , África do Sul , Adulto Jovem
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