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1.
Nat Rev Neurosci ; 25(5): 313-333, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594324

RESUMO

Compulsive behaviour, an apparently irrational perseveration in often maladaptive acts, is a potential transdiagnostic symptom of several neuropsychiatric disorders, including obsessive-compulsive disorder and addiction, and may reflect the severe manifestation of a dimensional trait termed compulsivity. In this Review, we examine the psychological basis of compulsions and compulsivity and their underlying neural circuitry using evidence from human neuroimaging and animal models. Several main elements of this circuitry are identified, focused on fronto-striatal systems implicated in goal-directed behaviour and habits. These systems include the orbitofrontal, prefrontal, anterior cingulate and insular cortices and their connections with the basal ganglia as well as sensoriomotor and parietal cortices and cerebellum. We also consider the implications for future classification of impulsive-compulsive disorders and their treatment.


Assuntos
Comportamento Compulsivo , Humanos , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/psicologia , Animais , Encéfalo/fisiopatologia , Encéfalo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Vias Neurais/fisiopatologia
2.
J Behav Ther Exp Psychiatry ; 84: 101960, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38513433

RESUMO

BACKGROUND AND OBJECTIVES: Rituals are common among healthy individuals and across cultures and often serve adaptive purposes. In individuals with obsessive-compulsive disorder (OCD), rituals become compulsive, time-consuming and distressing, and may lead to functional impairment. Previous research has examined the functions and characteristics of compulsive rituals, but there is paucity of in-depth, first-person reports about this topic. METHOD: We used a qualitative approach to explore thoughts, feelings, and behavioral patterns that characterize OCD rituals. Ten individuals with OCD participated in a semi-structured interview that focused on their most prominent compulsive ritual. The interviews were subjected to a thematic analysis. RESULTS: Eight themes emerged from the analysis and were organized in two main categories: Micro Level perspective, comprising triggers, attention, emotional changes, and stopping criteria; and Macro Level perspective, comprising feelings and perceptions, change over time, motives, and inhibitors. The findings shed light on the role of fixed rules and feelings of "completeness" in OCD rituals, the nature of emotional and attentional characteristics during rituals performance, and the evolution of compulsive rituals over time. LIMITATIONS: This study used a qualitative approach based on a small number of participants, which limits the generalizability of the findings. CONCLUSION: Our results, if replicated, may have clinical implications. The reported patterns of anxiety reduction during ritual performance may contribute to the fine-tuning of CBT for OCD. The findings concerning the nature of attention during ritual performance and the development of rituals over time may be important for understanding the mechanisms that maintain compulsive rituals.


Assuntos
Comportamento Ritualístico , Comportamento Compulsivo , Emoções , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Feminino , Masculino , Comportamento Compulsivo/fisiopatologia , Pessoa de Meia-Idade , Emoções/fisiologia , Pesquisa Qualitativa , Adulto Jovem , Pensamento/fisiologia
3.
Cogn Affect Behav Neurosci ; 24(2): 266-268, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453807

RESUMO

In this issue of Cognitive, Affective, and Behavioral Neuroscience, Pickenhan et al. (2024) discuss the need for translational studies to understand features underlying obsessive-compulsive disorder (OCD). They highlight the translational value of the observing-response task (ORT) for modeling functional and maladaptive checking behaviors, a common symptom of OCD.


Assuntos
Comportamento Compulsivo , Transtorno Obsessivo-Compulsivo , Pesquisa Translacional Biomédica , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Comportamento Compulsivo/fisiopatologia
4.
Psychophysiology ; 61(6): e14539, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38332720

RESUMO

Disorders marked by high levels of impulsivity and compulsivity have been linked to changes in performance monitoring, specifically the error-related negativity (ERN). We investigated the relationship between performance monitoring and individual differences in impulsivity and compulsivity. A total of 142 participants were recruited into four groups, each with different combinations of impulsivity and compulsivity, and they performed a flanker task to assess error-related brain activity. We defined error-related brain activity as ERN amplitude and theta power. Single-trial regression was employed to analyze the amplitude differences between incorrect and correct trials within the ERN time window. The findings revealed that impulsivity, compulsivity, and different measures of response processing exhibited distinct interactions, which were influenced by the configuration of impulsivity and compulsivity, but also depended on the measure of response processing. Specifically, high compulsivity predicted larger ERN amplitudes in individuals with low impulsivity, whereas high impulsivity had no significant effect on ERN amplitude in individuals with low compulsivity. Furthermore, when both impulsivity and compulsivity were high, no significant increase in ERN amplitude was observed; instead, there was a reduced difference between incorrect and correct trials. No significant differences were found for theta power. While the association between error-related brain activity and transdiagnostic markers or psychopathology may be smaller than generally assumed, considering the interaction between different transdiagnostic markers and their facets can enhance our understanding of the complex associations that arise during the investigation of neural correlates of performance monitoring, specifically the ERN.


Assuntos
Comportamento Compulsivo , Eletroencefalografia , Potenciais Evocados , Comportamento Impulsivo , Desempenho Psicomotor , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Feminino , Adulto Jovem , Comportamento Compulsivo/fisiopatologia , Potenciais Evocados/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Ritmo Teta/fisiologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Tempo de Reação/fisiologia , Adolescente
5.
Cogn Affect Behav Neurosci ; 24(2): 249-265, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316708

RESUMO

Obsessive-compulsive disorder (OCD), a highly prevalent and debilitating disorder, is incompletely understood in terms of underpinning behavioural, psychological, and neural mechanisms. This is attributable to high symptomatic heterogeneity; cardinal features comprise obsessions and compulsions, including clinical subcategories. While obsessive and intrusive thoughts are arguably unique to humans, dysfunctional behaviours analogous to those seen in clinical OCD have been examined in nonhuman animals. Genetic, ethological, pharmacological, and neurobehavioural approaches all contribute to understanding the emergence and persistence of compulsive behaviour. One behaviour of particular interest is maladaptive checking, whereby human patients excessively perform checking rituals despite these serving no purpose. Dysfunctional and excessive checking is the most common symptom associated with OCD and can be readily operationalised in rodents. This review considers animal models of OCD, the neural circuitries associated with impairments in habit-based and goal-directed behaviour, and how these may link to the compulsions observed in OCD. We further review the Observing Response Task (ORT), an appetitive instrumental learning procedure that distinguishes between functional and dysfunctional checking, with translational application in humans and rodents. By shedding light on the psychological and neural bases of compulsive-like checking, the ORT has potential to offer translational insights into the underlying mechanisms of OCD, in addition to being a platform for testing psychological and neurochemical treatment approaches.


Assuntos
Neuropsicologia , Transtorno Obsessivo-Compulsivo , Animais , Humanos , Comportamento Compulsivo/fisiopatologia , Condicionamento Operante/fisiologia , Modelos Animais de Doenças , Transtorno Obsessivo-Compulsivo/fisiopatologia , Neuropsicologia/métodos
6.
Elife ; 102021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34898427

RESUMO

When compulsions and obsessive thoughts took over her world, a graduate student found strength in her identity as a scientist.


Assuntos
Atitude do Pessoal de Saúde , Comportamento Compulsivo/diagnóstico , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/psicologia , Comportamento Compulsivo/terapia , Pesquisadores/psicologia , Estudantes de Medicina/psicologia , Adulto , Feminino , Humanos , Adulto Jovem
7.
Nat Commun ; 12(1): 6040, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654803

RESUMO

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine's therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity reduced compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. Finally, we demonstrate that ketamine blocks the exacerbation of grooming in KO mice caused by optogenetically inhibiting fronto-striatal activity. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine's therapeutic effects in OCD.


Assuntos
Comportamento Compulsivo/fisiopatologia , Corpo Estriado/metabolismo , Ketamina/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Asseio Animal/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neostriado/metabolismo , Neurônios/metabolismo , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/fisiopatologia
8.
J Neurol Neurosurg Psychiatry ; 92(12): 1313-1318, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510000

RESUMO

BACKGROUND: The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson's disease (PD) are understudied. OBJECTIVE: To investigate clinical predictors of STN-DBS effects on ICB. METHODS: In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into 'QUIP-RS improvement or worsening' and analysed between-group differences. RESULTS: We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the 'QUIP-RS worsening' group had more severe baseline impairment in the NMSS attention/memory domain. CONCLUSIONS: Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS. TRIAL REGISTRATION NUMBER: DRKS00006735.


Assuntos
Comportamento Compulsivo/psicologia , Estimulação Encefálica Profunda , Comportamento Impulsivo/fisiologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Comportamento Compulsivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Estudos Prospectivos , Qualidade de Vida
9.
Sci Rep ; 11(1): 15980, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354139

RESUMO

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.


Assuntos
Anorexia Nervosa/fisiopatologia , Tomada de Decisões/fisiologia , Substância Branca/fisiologia , Adolescente , Adulto , Anorexia Nervosa/psicologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Comportamento Compulsivo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Hábitos , Humanos , Masculino , Substância Branca/metabolismo , Adulto Jovem
10.
Exp Neurol ; 344: 113805, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34242631

RESUMO

Mild behavioral impairment (MBI), which can include compulsive behavior, is an early sign of Alzheimer's disease (AD), but its underlying neural mechanisms remain unclear. Here, we show that 3-5-month-old APP/PS1 mice display obsessive-compulsive disorder (OCD)-like behavior. The number of parvalbumin-positive (PV) interneurons and level of high gamma (γhigh) oscillation are significantly decreased in the striatum of AD mice. This is accompanied by enhanced ß-γhigh coupling and firing rates of putative striatal projection neurons (SPNs), indicating decorrelation between PV interneurons and SPNs. Local field potentials (LFPs) simultaneously recorded in prefrontal cortex (PFC) and striatum (Str) demonstrate a decrease in γhigh-band coherent activity and spike-field coherence in corticostriatal circuits of APP/PS1 mice. Furthermore, levels of GABAB receptor (GABABR), but not GABAA receptor (GABAAR), and glutamatergic receptors, were markedly reduced, in line with presymptomatic AD-related behavioral changes. These findings suggest that MBI occurs as early as 3-5 months in APP/PS1 mice and that altered corticostriatal synchronization may play a role in mediating the behavioral phenotypes observed.


Assuntos
Doença de Alzheimer/fisiopatologia , Comportamento Compulsivo/fisiopatologia , Corpo Estriado/fisiopatologia , Interneurônios/fisiologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Comportamento Compulsivo/metabolismo , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Vias Neurais/metabolismo , Córtex Pré-Frontal/metabolismo , Presenilinas/genética , Receptores de GABA-B/metabolismo
11.
J Neurosci ; 41(30): 6539-6550, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34131033

RESUMO

Compulsive individuals have deficits in model-based planning, but the mechanisms that drive this have not been established. We examined two candidates-that compulsivity is linked to (1) an impaired model of the task environment and/or (2) an inability to engage cognitive control when making choices. To test this, 192 participants performed a two-step reinforcement learning task with concurrent EEG recordings, and we related the neural and behavioral data to their scores on a self-reported transdiagnostic dimension of compulsivity. To examine subjects' internal model of the task, we used established behavioral and neural responses to unexpected events [reaction time (RT) slowing, P300 wave, and parietal-occipital alpha band power] measured when an unexpected transition occurred. To assess cognitive control, we probed theta power at the time of initial choice. As expected, model-based planning was linked to greater behavioral (RT) and neural (alpha power, but not P300) sensitivity to rare transitions. Critically, the sensitivities of both RT and alpha to task structure were weaker in those high in compulsivity. This RT-compulsivity effect was tested and replicated in an independent pre-existing dataset (N = 1413). We also found that mid-frontal theta power at the time of choice was reduced in highly compulsive individuals though its relation to model-based planning was less pronounced. These data suggest that model-based planning deficits in compulsive individuals may arise, at least in part, from having an impaired representation of the environment, specifically how actions lead to future states.SIGNIFICANCE STATEMENT Compulsivity is linked to poorer performance on tasks that require model-based planning, but it is unclear what precise mechanisms underlie this deficit. Do compulsive individuals fail to engage cognitive control at the time of choice? Or do they have difficulty in building and maintaining an accurate representation of their environment, the foundation needed to behave in a goal-directed manner? With reaction time and EEG measures in 192 individuals who performed a two-step decision-making task, we found that compulsive individuals are less sensitive to surprising action-state transitions, where they slow down less and show less alpha band suppression following a rare transition. These findings implicate failures in maintaining an accurate model of the world in model-based planning deficits in compulsivity.


Assuntos
Encéfalo/fisiopatologia , Comportamento Compulsivo/fisiopatologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia
12.
PLoS One ; 16(6): e0252563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34081731

RESUMO

The present study examines the phenomenon of compensative and compulsive buying among online shoppers. Firstly, the obtained empirical data make it possible to estimate the prevalence of compensative and compulsive buying among the general population of Poles aged 15 years old and over, with the sample split into users and non-users of the e-commerce market offer. Secondly, the conducted analysis shows to what extent the prevalence of compulsive and compensative buying is differentiated by the frequency of online shopping, by the extent of the expenditures on online shopping compared with offline shopping, by attitudes towards online shopping, and by sociodemographic conditions (gender, age, monthly net income of household). The findings come from a survey conducted in 2019 based on a nationwide statistically representative sample of 1,000 Poles aged 15 years old and over. Drawing on this survey based on the German Compulsive Buying Indicator (GCBI), the prevalence of compulsive buying is observed at about 3% and compensative buying at about 12%. Dividing the general population into online and offline shoppers, one can see serious differences between both target groups; the share of compulsive and compensative buyers in the segment of online shoppers amounts to 3.6% and 16.9%, while among non-online shoppers- 3.3% and 10.1%. The strongest susceptibility to compulsive buying is characteristic of female online shoppers having very positive attitudes towards online shopping and doing online shopping very frequently.


Assuntos
Comércio , Comportamento Compulsivo/fisiopatologia , Adolescente , Adulto , Comportamento Compulsivo/epidemiologia , Comportamento do Consumidor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
13.
Addict Biol ; 26(6): e13041, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33955649

RESUMO

Excessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol-preferring rats were pre-exposed intermittently to a two-bottle choice procedure and trained on a seeking-taking chained schedule of alcohol reinforcement until some individuals developed punishment-resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome-devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome devaluation (were more habitual) were more likely to show punishment-resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals who have preferentially engaged the habit system.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/fisiopatologia , Corpo Estriado/metabolismo , Comportamento de Procura de Droga/fisiologia , Animais , Comportamento Compulsivo/fisiopatologia , Condicionamento Operante , Hábitos , Aprendizagem/fisiologia , Masculino , Ratos , Autoadministração
14.
Sci Rep ; 11(1): 9442, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941812

RESUMO

Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals. Neural mechanisms underlying these disturbances are unclear; however, striatal dopamine is implicated in regulation of sensorimotor gating and OCD pathophysiology. The goal of this study was to examine the relationships between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels in Sapap3 knockout mice (KOs), a widely used preclinical model system for OCD research. We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs. Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC). Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7 months of age. Through detailed characterization of individual differences in OCD-relevant behavioral and neurochemical measures, our findings suggest that NAcC dopamine receptor changes may be involved in disruption of sensorimotor gating and compulsive behavior relevant to OCD.


Assuntos
Comportamento Compulsivo/fisiopatologia , Proteínas do Tecido Nervoso/genética , Transtorno Obsessivo-Compulsivo/fisiopatologia , Inibição Pré-Pulso/fisiologia , Receptores Dopaminérgicos/fisiologia , Animais , Dopamina/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Núcleo Accumbens/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Receptores Dopaminérgicos/genética , Filtro Sensorial/fisiologia
15.
J Neurochem ; 157(5): 1525-1546, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33931861

RESUMO

Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top-down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug-induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico-striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug-motivated behaviours that might explain individual risk for addiction.


Assuntos
Comportamento Aditivo/fisiopatologia , Comportamento Aditivo/psicologia , Química Encefálica/fisiologia , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/psicologia , Comportamento Impulsivo , Neuroquímica , Neurotransmissores/fisiologia , Animais , Humanos , Transtornos Relacionados ao Uso de Substâncias
16.
Am J Psychiatry ; 178(5): 459-468, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33726523

RESUMO

OBJECTIVE: Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings. METHODS: After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe. RESULTS: cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS. CONCLUSIONS: Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.


Assuntos
Comportamento Compulsivo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Ritmo Teta , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Transtornos Dismórficos Corporais/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Distribuição Aleatória , Tricotilomania/fisiopatologia , Adulto Jovem
17.
Nat Med ; 27(2): 232-238, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462447

RESUMO

Nearly one billion people worldwide suffer from obsessive-compulsive behaviors1,2, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive-compulsive behaviors as maladaptive habit learning3,4, which may be associated with abnormal beta-gamma neurophysiology of the orbitofrontal-striatal circuitry during reward processing5,6. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta-gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive-compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive-compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive-compulsive behavior, suggest a unifying functional role of rhythms in the beta-gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.


Assuntos
Corpo Estriado/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/terapia , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Elétrica Nervosa Transcutânea , Adulto , Mapeamento Encefálico , Comportamento Compulsivo/diagnóstico por imagem , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/terapia , Corpo Estriado/fisiopatologia , Corpo Estriado/efeitos da radiação , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/efeitos da radiação
18.
Genes Brain Behav ; 20(1): e12594, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31177612

RESUMO

While Alzheimer's disease (AD) is traditionally associated with deficits in episodic memory, early changes in other cognitive domains, such as attention, have been gaining interest. In line with clinical observations, some animal models of AD have been shown to develop attentional deficits, but this is not consistent across all models. The APPswe/PS1ΔE9 (APP/PS1) mouse is one of the most commonly used AD models and attention has not yet been scrutinised in this model. We set out to assess attention using the 5-choice serial reaction time task (5CSRTT) early in the progression of cognitive symptoms in APP/PS1 mice, using clinically translatable touchscreen chambers. APP/PS1 mice showed no attentional changes across 5CSRTT training or any probes from 9 to 11 months of age. Interestingly, APP/PS1 mice showed increased impulsive and compulsive responding when task difficulty was high. This suggests that while the APP/PS1 mouse model may not be a good model of attentional changes in AD, it may be useful to study the early changes in impulsive and compulsive behaviour that have been identified in patient studies. As these changes have not previously been reported without attentional deficits in the clinic, the APP/PS1 mouse model may provide a unique opportunity to study these specific behavioural changes seen in AD, including their mechanistic underpinnings and therapeutic implications.


Assuntos
Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Atenção , Comportamento Compulsivo/genética , Presenilina-1/genética , Doença de Alzheimer/genética , Animais , Comportamento Compulsivo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
PLoS One ; 15(12): e0243912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351837

RESUMO

INTRODUCTION: The Gilles de la Tourette Syndrome-Quality of Life Scale (GTS-QOL) is a self-rated disease-specific questionnaire to assess health-related quality of life of subjects with GTS. Our aim was to perform the cross-cultural adaptation of the GTS-QOL into French and to assess its psychometric properties. METHODS: The GTS-QOL was cross-culturally adapted by conducting forward and backward translations, following international guidelines. The psychometric properties of the GTS-QOL-French were assessed in 109 participants aged 16 years and above with regard to factor structure, internal consistency, reliability and convergent validity with the MOVES (Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey) and the WHOQOL-BREF (World Health Organization Quality of Life Brief). RESULTS: Exploratory factor analysis of the GTS-QOL-French resulted in a 6-factor solution and did not replicate the original structure in four subscales. The results showed good acceptability (missing values per subscale ranging from 0% to 0.9%), good internal consistency (Cronbach's alpha ranging from 0.68 to 0.94) and good test-retest reliability (intraclass correlation coefficients ranging from 0.70 to 0.81). Convergent validity with the MOVES and WHOQOL-BREF scales showed high correlations. DISCUSSION: Our study provides evidence of the good psychometric properties of the GTS-QOL-French. The cross-cultural adaptation and validation of this specific instrument will make it possible to assess health-related quality of life in French-speaking subjects with GTS. The GTS-QOL-French could be recommended for use in future research.


Assuntos
Comportamento Compulsivo/fisiopatologia , Psicometria/métodos , Síndrome de Tourette/diagnóstico , Adolescente , Adulto , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/fisiopatologia , Organização Mundial da Saúde , Adulto Jovem
20.
J Behav Addict ; 9(3): 797-807, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33006958

RESUMO

BACKGROUND: Desire thinking is a voluntary cognitive process that involves the perseverative focus on memories, images and information related to a desired target. The aim of the present study was to validate the Hebrew version of the Desire Thinking Questionnaire (DTQ; Caselli & Spada, 2011) in a sample of adolescents and to investigate its relationship with measures of thought suppression, impulsivity and individual-based compulsive sexual behaviour. METHODS: In Study 1, a convenience sample of 718 adolescents completed the newly translated Desire Thinking Questionnaire in Hebrew (DTQ-H) and results were subjected to an Exploratory Factor Analysis (EFA). In Study 2, a convenience sample of 379 adolescents completed a battery of questionnaires including the DTQ-H. A Confirmatory Factors Analysis was performed on the DTQ-H and validity was ascertained by correlating with other measures. RESULTS: In Study 1, a 9-item two-factor structure was identified. A 6-item two-factor structure was confirmed in Study 2. Results also indicated that the DTQ-H has acceptable levels of reliability, and good concurrent and incremental validity in predicting compulsive sexual behaviour. CONCLUSIONS: The 6-item DTQ-H appears to be a reliable and valid measure of desire thinking and may be used also on adolescents - an understudied population.


Assuntos
Comportamento do Adolescente/fisiologia , Comportamento Compulsivo/diagnóstico , Comportamento Compulsivo/fisiopatologia , Psicometria/normas , Comportamento Sexual/fisiologia , Pensamento/fisiologia , Adolescente , Comparação Transcultural , Feminino , Humanos , Israel , Masculino , Reprodutibilidade dos Testes
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