RESUMO
The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.
Assuntos
Transtornos Mentais , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Adulto , Adolescente , Humanos , Criança , Encéfalo , Transtornos Mentais/genética , Transtornos Mentais/patologia , Envelhecimento/genética , Imageamento por Ressonância Magnética , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologiaRESUMO
This paper describes the development and validation of the Autonomy Scale Amsterdam (ASA). We propose that a new measure of autonomy is needed and, as such, we developed and validated an autonomy scale relevant for psychiatry. Based on literature, an expert meeting and three samples of the general population (N = 298, N = 207, N = 309) we provide evidence (a) that supports a 6-factor structure model as a better fit than alternative models with a high reliability to capture the concept of autonomy consisting of: Self-integration, Engagement with life, Goal-directedness, Self-control, External constraints and Social support, (b) for the scale's convergent and discriminant validity with constructs in autonomy's nomological network and (c) for the scale's criterion validity with well-established well-being outcomes, and (d) that the measure is not redundant with a prior measure of autonomy, the autonomy-connectedness scale, and demonstrates incremental validity in the prediction of mental health over and above an existing measure of autonomy. Taken together, the results suggest that the ASA is a useful scale that shows positive evidence of psychometric quality to measure autonomy in a sample of the general population (total N = 856), accounting for a unique predictive value over and above an existing measure of autonomy concerning several mental health outcomes. The ASA can further help our understanding of the role of autonomy in mental disorders.
Assuntos
Transtornos Mentais , Humanos , Reprodutibilidade dos Testes , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Saúde Mental , Motivação , Apoio Social , Psicometria/métodos , Inquéritos e QuestionáriosRESUMO
Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.
Assuntos
Alcoolismo , Humanos , Feminino , Masculino , Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Consumo de Bebidas Alcoólicas , Imageamento por Ressonância Magnética/métodosRESUMO
Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.
Assuntos
Transtorno Bipolar/patologia , Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Esquizofrenia/patologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Esquizofrenia/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagemRESUMO
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.
Assuntos
Alcoolismo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Estudos Multicêntricos como Assunto , Neuroimagem , Putamen/diagnóstico por imagem , Córtex Cerebral/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Neuroimagem/métodos , Neuroimagem/normas , Putamen/patologia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. AIMS: We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. METHOD: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. RESULTS: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. CONCLUSIONS: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.
Assuntos
Alcoolismo , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/epidemiologia , Encéfalo/diagnóstico por imagem , Estudo de Associação Genômica Ampla , Humanos , Fumar/efeitos adversosRESUMO
AIMS: Compulsivity is a common phenotype among psychiatric disorders, such as obsessive-compulsive disorder (OCD) and gambling disorder (GD). Deficiencies in metacognition, such as the inability to estimate one's performance via confidence judgments could contribute to pathological decision-making. Earlier research has shown that patients with OCD exhibit underconfidence, while patients with GD exhibit overconfidence. Moreover, it is known that motivational states (e.g. monetary incentives) influence metacognition, with gain (respectively loss) prospects increasing (respectively decreasing) confidence. Here, we reasoned that OCD and GD symptoms might correspond to an exacerbation of this interaction between metacognition and motivation. METHODS: We hypothesized GD's overconfidence to be exaggerated during gain prospects, while OCD's underconfidence to be worsened in loss context, which we expected to see represented in ventromedial prefrontal cortex (VMPFC) blood-oxygen-level-dependent activity. We tested those hypotheses in a task-based functional magnetic resonance imaging (fMRI) design (27 patients with GD, 28 patients with OCD, 55 controls). The trial is registered in the Dutch Trial Register (NL6171). RESULTS: We showed increased confidence for patients with GD versus patients with OCD, which could partly be explained by sex and IQ. Although our primary analyses did not support the hypothesized interaction between incentives and groups, exploratory analyses did show increased confidence in patients with GD specifically in gain context. fMRI analyses confirmed a central role for VMPFC in the processing of confidence and incentives, but no differences between the groups. CONCLUSION: Patients with OCD and those with GD reside at opposite ends of the confidence spectrum, while no interaction with incentives was found, nor group differences in neuronal processing of confidence.
Assuntos
Jogo de Azar , Metacognição , Transtorno Obsessivo-Compulsivo , Humanos , Imageamento por Ressonância Magnética , Motivação , Transtorno Obsessivo-Compulsivo/diagnóstico por imagemRESUMO
Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.
Assuntos
Córtex Cerebelar/patologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Adulto , Alcoolismo/diagnóstico por imagem , Comportamento Aditivo/diagnóstico por imagem , Encéfalo/patologia , Espessura Cortical do Cérebro , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Núcleo Accumbens/patologia , Tabagismo/diagnóstico por imagem , Adulto JovemRESUMO
Dopamine is central to a number of cognitive functions and brain disorders. Given the cost of neurochemical imaging in humans, behavioural proxy measures of dopamine have gained in popularity in the past decade, such as spontaneous eye blink rate (sEBR). Increased sEBR is commonly associated with increased dopamine function based on pharmacological evidence and patient studies. Yet, this hypothesis has not been validated using in vivo measures of dopamine function in humans. To fill this gap, we measured sEBR and striatal dopamine synthesis capacity using [18 F]DOPA PET in 20 participants (nine healthy individuals and 11 pathological gamblers). Our results, based on frequentist and Bayesian statistics, as well as region-of-interest and voxel-wise analyses, argue against a positive relationship between sEBR and striatal dopamine synthesis capacity. They show that, if anything, the evidence is in favour of a negative relationship. These results, which complement findings from a recent study that failed to observe a relationship between sEBR and dopamine D2 receptor availability, suggest that caution and nuance are warranted when interpreting sEBR in terms of a proxy measure of striatal dopamine.
Assuntos
Piscadela/fisiologia , Corpo Estriado/metabolismo , Dopamina/metabolismo , Receptores de Dopamina D2/metabolismo , Adulto , Olho/metabolismo , Jogo de Azar/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodosRESUMO
BACKGROUND: High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained interest as a neuromodulation treatment technique for alcohol dependence. Single sessions of HF-rTMS have consistently shown to decrease craving for substances. However, the results of randomized controlled clinical trials investigating the effect of multiple HF-rTMS sessions in alcohol dependence on abstinence rates and craving are inconsistent. Furthermore, they lack information on the effect of HF-rTMS on cognition and brain functioning. METHODS: A single center, single blind, randomized controlled trial with 80 abstinent alcohol dependent subjects in treatment randomized (1:1) to either treatment as usual (TAU) plus ten sessions of active HF-rTMS or TAU plus 10 sessions of placebo/ sham HF-rTMS will be performed. The effects of ten HF-rTMS sessions on craving and neurocognitive functions are obtained. In addition a subset of participants will undergo an MR scanning session before the first and after the last HF-rTMS session in order to investigate the effect of ten HF-rTMS sessions on brain functioning. The primary outcome is the continued abstinence rate after the add-on HF-rTMS treatment. DISCUSSION: This study uses a randomized controlled trial to examine the clinical, neurocognitive and brain functioning effects of ten add-on HF-rTMS sessions in alcohol dependent individuals in treatment. If the add-on treatment is effective, this may add to the evidence needed for approval of this additional treatment method for alcohol dependence by regulatory authorities. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR), NTR5291 , 6-July-2015.
Assuntos
Alcoolismo/diagnóstico por imagem , Alcoolismo/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Alcoolismo/epidemiologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Países Baixos/epidemiologia , Córtex Pré-Frontal/diagnóstico por imagem , Método Simples-Cego , Resultado do TratamentoRESUMO
Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general.
Assuntos
Gânglios da Base/patologia , Comportamento Aditivo/patologia , Jogo de Azar/patologia , Córtex Pré-Frontal/patologia , Substância Branca/patologia , Adulto , Gânglios da Base/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Substância Branca/diagnóstico por imagemRESUMO
This study aims at the assessment of alexithymia and anger levels in 100 treatment-seeking pathological gamblers compared with controls, who were matched for age, gender and education. Furthermore a positive correlation between alexithymia, anger and severity of gambling disorder and a relationship between gambling behaviour and anger after controlling for alexithymia, are investigated. Finally the role that gender plays in anger in pathological gamblers was also evaluated. Psychological assessment includes the South Oaks Gambling Screen, State-Trait Anger Expression Inventory-2 and the twenty-item Toronto Alexithymia Scale. Statistical analysis of the results shows a higher level of anger in pathological gamblers than in controls, together with alterations in emotional processing. Severity of gambling behaviour positively correlates with alexithymia scores, state-anger and trait-anger. Moreover, a significant contribution of anger in predicting gambling behaviour was suggested after controlling for alexithymia. In conclusion, anger and alexithymia must be regarded as relevant components of the assessment of pathological gamblers, in order to select the best therapeutical strategies to prevent self-defeating behaviours and to reduce drop-out from treatments.
Assuntos
Sintomas Afetivos/psicologia , Ira , Comportamento Aditivo/psicologia , Emoções , Jogo de Azar/psicologia , Adulto , Feminino , Humanos , Masculino , Inventário de PersonalidadeRESUMO
Cognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol-dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task-related functional connectivity between these areas was assessed. There were no significant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence.
Assuntos
Alcoolismo/fisiopatologia , Mapeamento Encefálico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Cognição/efeitos dos fármacos , Imageamento por Ressonância Magnética , Adulto , Cognição/fisiologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Substância Branca/efeitos dos fármacos , Substância Branca/fisiopatologiaRESUMO
BACKGROUND: Patients with alcohol dependence (AD) and pathological gambling (PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning. METHODS: Thirty-three alcohol-dependent patients (ADs), 28 pathological gamblers (PGs), and 18 healthy controls (HCs) performed a contingency learning task in which they learned stimulus-reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal-Wallis rank-sum tests. Regression analyses were performed to compare learning curves. RESULTS: PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task. CONCLUSIONS: Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies.
Assuntos
Alcoolismo/psicologia , Extinção Psicológica , Jogo de Azar/psicologia , Recompensa , Adulto , Estudos de Casos e Controles , Aprendizagem por Discriminação , Retroalimentação Psicológica , Humanos , Masculino , Pessoa de Meia-Idade , Reversão de Aprendizagem , Adulto JovemRESUMO
Background and aims: Decisions and learning processes are under metacognitive control, where confidence in one's actions guides future behaviour. Indeed, studies have shown that being more confident results in less action updating and learning, and vice versa. This coupling between action and confidence can be disrupted, as has been found in individuals with high compulsivity symptoms. Patients with Gambling Disorder (GD) have been shown to exhibit both higher confidence and deficits in learning. Methods: In this study, we tested the hypotheses that patients with GD display increased confidence, reduced action updating and lower learning rates. Additionally, we investigated whether the action-confidence coupling was distorted in patients with GD. To address this, 27 patients with GD and 30 control participants performed a predictive inference task designed to assess action and confidence dynamics during learning under volatility. Action-updating, confidence and their coupling were assessed and computational modeling estimated parameters for learning rates, error sensitivity, and sensitivity to environmental changes. Results: Contrary to our expectations, results revealed no significant group differences in action updating or confidence levels. Nevertheless, GD patients exhibited a weakened coupling between confidence and action, as well as lower learning rates. Discussion and conclusions: This suggests that patients with GD may underutilize confidence when steering future behavioral choices. Ultimately, these findings point to a disruption of metacognitive control in GD, without a general overconfidence bias in neutral, non-incentivized volatile learning contexts.
Assuntos
Jogo de Azar , Metacognição , HumanosRESUMO
Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19â¯311 participants, including 13â¯812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
Assuntos
Biomarcadores , Sinais (Psicologia) , Imageamento por Ressonância Magnética , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/metabolismo , Neuroimagem FuncionalRESUMO
BACKGROUND: Recent research findings suggest that heavy alcohol use is associated with alterations of the hypothalamic-pituitary-adrenal axis and autonomic nervous system function and that early abstinence is associated with blunted stress responsiveness. METHODS: This study investigated abstinent alcohol-dependent participants (AADs; n = 31), who had a drinking history of levels about 97 drinks per week (abstinence range: 2 weeks to 24 months), actively drinking problem drinkers (PRDs; n = 23), who reported drinking levels about 47 drinks per week and who were abstinent for at least 24 hours, and healthy control (HC) participants (n = 20). It was investigated how participants responded to a psychosocial stress task. All of them were exposed to a modified Trier Social Stress Test. Salivary cortisol, heart rate, skin conductance levels, and negative affect were assessed as stress indicators. RESULTS: AADs showed stress reactions comparable to HC participants, whereas active PRDs showed increased heart rate and cortisol stress responses. In the AAD group, duration of abstinence was positively related to cortisol stress responses. CONCLUSIONS: Active PRDs showed increased responses to psychosocial stress. Results indicate that duration of abstinence is a key factor when analyzing and interpreting stress responses in alcohol abuse and dependence.
Assuntos
Transtornos Relacionados ao Uso de Álcool/psicologia , Frequência Cardíaca , Hidrocortisona/metabolismo , Estresse Psicológico , Adulto , Abstinência de Álcool/psicologia , Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/fisiopatologia , Fatores de Tempo , Adulto JovemRESUMO
Gambling disorder (GD) is a behavioural addiction characterized by impairments in decision-making, favouring risk- and reward-prone choices. One explanatory factor for this behaviour is a deviation in attentional processes, as increasing evidence indicates that GD patients show an attentional bias toward gambling stimuli. However, previous attentional studies have not directly investigated attention during risky decision-making. 26 patients with GD and 29 healthy matched controls (HC) completed a mixed gambles task combined with eye-tracking to investigate attentional biases for potential gains versus losses during decision-making under risk. Results indicate that compared to HC, GD patients gambled more and were less loss averse. GD patients did not show a direct attentional bias towards gains (or relative to losses). Using a recent (neuro)economics model that considers average attention and trial-wise deviations in average attention, we conducted fine-grained exploratory analyses of the attentional data. Results indicate that the average attention for gains in GD patients moderated the effect of gain value on gambling choices, whereas this was not the case for HC. GD patients with high average attention for gains started gambling at less high gain values. A similar trend-level effect was found for losses, where GD patients with high average attention for losses stopped gambling at lower loss values. This study gives more insight into how attentional processes in GD play a role in gambling behaviour, which could have implications for the development of future treatments focusing on attentional training or for the development of interventions that increase the salience of losses.
Assuntos
Comportamento Aditivo , Jogo de Azar , Humanos , Tomada de Decisões , Tecnologia de Rastreamento Ocular , AtençãoRESUMO
The development of addictive behaviors has been suggested to be related to a transition from goal-directed to habitual decision making. Stress is a factor known to prompt habitual behavior and to increase the risk for addiction and relapse. In the current study, we therefore used functional MRI to investigate the balance between goal-directed 'model-based' and habitual 'model-free' control systems and whether acute stress would differentially shift this balance in gambling disorder (GD) patients compared to healthy controls (HCs). Using a within-subject design, 22 patients with GD and 20 HCs underwent stress induction or a control condition before performing a multistep decision-making task during fMRI. Salivary cortisol levels showed that the stress induction was successful. Contrary to our hypothesis, GD patients did not show impaired goal-directed 'model-based' decision making, which remained similar to HCs after stress induction. Bayes factors provided three times more evidence against a difference between the groups or a group-by-stress interaction on the balance between model-based and model-free decision making. Similarly, no differences were found between groups and conditions on the neural estimates of model-based or model-free decision making. These results challenge the notion that GD is related to an increased reliance on habitual (or decreased goal-directed) control, even during stress.
Assuntos
Jogo de Azar , Humanos , Jogo de Azar/diagnóstico por imagem , Objetivos , Imageamento por Ressonância Magnética , Teorema de Bayes , Tomada de DecisõesRESUMO
Background and aims: People with Gambling Disorder (GD) often make risky decisions and experience cognitive distortions about gambling. Moreover, people with GD have been shown to be overly confident in their decisions, especially when money can be won. Here we investigated if and how the act of making a risky choice with varying monetary stakes impacts confidence differently in patients with GD (n = 27) relative to healthy controls (HCs) (n = 30). Methods: We used data from our previous mixed-gamble study, in which participants were given the choice of a certain option or a 50/50 gamble with potential gains or losses, after which they rated their confidence. Results: While HCs were more confident when making certain than risky choices, GD patients were specifically more confident when making risky choices than certain choices. Notably, relative to HCs, confidence of patients with GD decreased more strongly with higher gain values when making a certain choice, suggesting a stronger fear of missing out or "anticipated regret" of missing out on potential gains when rejecting the risky choice. Discussion: The current findings highlight the potential relevance of confidence and "regret" as cognitive mechanisms feeding into excessive risk-taking as seen in GD. Moreover, this study adds to the limited previous work investigating how confidence is affected in value-based risky contexts.