O amor patológico caracterizado pelo comportamento de prestar cuidados e atenção ao parceiro, de maneira repetitiva e desprovida de controle, em um relacionamento amoroso é um quadro pouco estudado cientificamente, apesar de não ser raro e de gerar sofrimento importante. Com o intuito de compreender os aspectos clínicos e de personalidade associados ao amor patológico, os seguintes fatores foram analisados: impulsividade, personalidade, satisfação com o relacionamento amoroso, estilo de amor e tipo de apego. Além de revisar a literatura, os dados obtidos, por meio da aplicação de vários instrumentos em 50 sujeitos com amor patológico e 39 sujeitos saudáveis evidenciaram que indivíduos com amor patológico apresentam alta impulsividade (p<0.001; Escala de Impulsividade de Barratt), elevada auto-transcendência, isto é, senso de fazer parte de uma realidade maior (p<0.001; Inventário de Temperamento e Caráter), e manutenção de relacionamento amoroso com baixa qualidade (p<0.001; Escala de Avaliação do Relacionamento Adaptada). Assim, essa população necessita, por parte dos centros de tratamento especializados, de avaliação e abordagem terapêutica efetivas, as quais devem contemplar as características clínicas e de personalidade específicas dessa condição / Pathological love characterized by the behavior of providing repetitive and uncontrolled care and attention to the partner in a romantic relationship is a rarely studied condition, despite not being rare and causing suffering. In order to know the clinical and personality aspects associated with pathological love, the following factors were analyzed: impulsivity, personality, satisfaction with romantic relationship, love style, and type of attachment. Besides revisiting the literature, the data obtained from the application of various instruments in 50 subjects with pathological love and 39 healthy subjects showed that individuals with pathological love present higher impulsivity (p<0.001; Barratt Impulsiveness Scale), elevated selftranscendence, that is, hold sense of communion with a wider reality (p<0.001; Temperament and Character Inventory) and keep dissatisfactory romantic relationships (p<0.001; Adapted Relationship Assessment Scale). Hence, this population needs effective assessment and therapeutic strategies, which must take into account the specific clinical and personality characteristics of the condition

A Compra Compulsiva (CC) está atualmente classificada como um transtorno do controle dos impulsos não classificados em outro local (TCI). A prevalência das CC é estimada em cerca de 5% da população geral e é identificada com maior frequência no gênero feminino. O comportamento repetitivo e crônico do comportamento de gastar descontroladamente gera consequênias negativas ao indivíduo, além dos elevados índices de comorbidades com transtorno de humos, ansiedade e outros TCIs, o que contribui para manter a divergência existente sobre a classificação da CC. Tem sido proposto que CC deve ser classificada como um TCI, ou como uma sub-síndrome do transtorno afetivo bipolar (TAB), ou ainda como uma variante do transtorno obsessivo-compulsivo (TOC) semelhante ao armazenamento compulsivo. O objetivo deste estudo é investigar qual classificação pode ser mais adequada para a CC. Para isso, adotamos duas abordagens: a primeira abordagem é a investigação das categorias diagnósticas para identificar as comorbidades psiquiátricas; a segunda abordagem refere-se as dimensões psicopatológicas em que comparamos impulsividade, sintomas obsessivo-compulsivos, instabilidade afetiva e armazenamento em pacientes com CC, TOC e TAB. Foram selecionados 80 pacientes (24 CC, 35 TOC e 21 TAB que não estivessem em mania nem hipomania) primeiramente foram avaliados de acordo com o SCID-CV e da seção especial para TCI e depois responderam os questionários de autopreenchimento. Realizamos duas análises: categorial e dimensional. Na análise categorial houve um equilibrio de associação entre os três grupos diagnósticos, e as comorbidades psiquiátricas apresentadas pelos três grupos diagnósticos foram congruentes com as descritas na literatura. Na análise dimensional os pacientes de CC apresentaram escores significativamente mais altos em todas as medidas de impulsividade e na aquisição, mas não nas outras sub-dimensões do armazenamento compulsivo, amontoamento e dificuldade em descartar. Pacientes bipolares pontuaram mais na dimensão mania da escala SCI-MOODS. Pacientes com TOC pontuaram mais nos sintomas obsessivo-compulsivos, e principalmente nas dimensões contaminação/lavagem e checagem da escala Pádua Inventory; no entanto, eles não apresentaram maior pontuação em nenhuma dimensão do armazenamento compulsivo. Um modelo discriminante foi construído com essas variáveis e classificou corretamente os pacientes de CC (79%), TOC (77%) e TAB (71%). Considerando os resultados da análise categorial cada um dos transtornos apresentou uma agregação categorial distinta, e na análise dimensional os pacientes com CC revelaram ter aquisição impulsiva, assemelhando-se aos TCI ao invés de TOC ou TAB. Sintomas maníacos foram bem distintos nos pacientes bipolares, assim como pacientes com TOC apresentaram mais obsessão e compulsão. Sintomas de armazenamento com exceção da aquisição não foram particularmente associados a qualquer grupo diagnóstico / Compulsive Buying (CB) is currently classified as an impulse control disorder not elsewhere classified (ICD). The prevalence of CB is estimated at around 5% of the general population and is identified with greater frequency in females. The chronic repetitive behavior and the behavior of spending wildly generates negative consequences to the individual, in addition to high rates of comorbidity with mood disorder, anxiety and other ICDs, which helps to maintain the existing disagreement on the classification of CB. It has been proposed that CB should be classified as an ICD, or as a sub-syndrome of bipolar disorder (BD), or as a variant of obsessive-compulsive disorder (OCD), similar to compulsive hoarding. The aim of this study is to investigate which classification is best suited for CB. For this, we adopt two approaches: the first approach is the investigation of the diagnostic categories to identify psychiatric comorbidities, the second approach refers to the psychopathological dimensions in which we compared impulsivity, obsessive-compulsive symptoms, affective instability and hoarding in patients with CB, OCD and BD. We selected 80 patients (24 CB, 35 OCD and 21 BD who were not in mania or hypomania) were first evaluated according to the SCID-CV and the special section to TCI, then answered the self-report questionnaires. We performed two analyses: categorical and dimensional. In categorical analysis, there was a balance of association between the three diagnostic groups, and psychiatric comorbidities by the three diagnostic groups were consistent with those described in the literature. In dimensional analysis of CB patients, there were significantly higher scores in all measures of impulsivity and the acquisition, but not in other sub-dimensions of the compulsive hoarding, clutter and difficulty discarding. Bipolar patients scored higher on the mania dimension from the SCI-MOODS scale. OCD patients scored higher on obsessive-compulsive symptoms, and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory scale; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients of CB (79%), OCD (77%) and BD (71%). Considering the results of categorical analysis, each of the disorders presented a distinct clustering categorical, and dimensional analysis in patients with CB reported having impulsive acquisition, resembling the TCI instead of OCD or BD. Manic symptoms were distinctive of BD patients, and patients with OCD were distinctive obsession and compulsion. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group

京都大学 / 新制・課程博士 / 博士(理学) / 甲第25485号 / 理博第5066号 / 新制||理||1722(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 明里 宏文, 准教授 足立 幾磨, 教授 今井 啓雄 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

Tricotilomania (TTM) é um transtorno prevalente e incapacitante caracterizado pelo repetitivo arrancar de cabelo, sendo, atualmente, classificada no grupo dos transtornos relacionados ao transtorno obsessivo-compulsivo (APA, 2013). Diversos estudos foram apresentados na literatura clínica, sugerindo que a TTM é mais comum do que se acreditava e várias propostas de tratamento foram apresentadas. As pesquisas do comportamento em pacientes com TTM têm focalizado seus fatores mantenedores. Entretanto, devemos considerar o potencial papel das cognições que podem operar junto com variáveis de comportamento, na etiologia e manutenção da TTM. Exceto por três estudos controlados para Terapia de Reversão de Hábito, até o momento, não foram publicados estudos controlados sobre o uso de Terapia Cognitivo-comportamental (TCC) em TTM; apenas relatos e séries de casos. O presente estudo teve como objetivo testar um programa manualizado de TCC em Grupo (TCC-G) para portadores de TTM, diagnosticados de acordo com o Manual Diagnóstico e Estatístico de Doenças Mentais - 4ª Edição (DSM-IV). Os pacientes com TTM foram alocados aleatoriamente em um dos dois grupos, sendo que um grupo experimental (n=22) participou de TCC-G e o outro grupo controle (n=22) participou de Terapia de Apoio em Grupo (TA-G). Durante o estudo, os participantes do grupo experimental participaram de vinte e duas sessões de um programa de TCC-G manualizado. A principal variável de desfecho foi a Massachusetts General Hospital Hair Pulling Scale (MGH-HPS), as demais variáveis secundárias de desfecho foram: Inventário de Depressão de Beck (Beck Depression Inventory - BDI), Inventário de Ansiedade de Beck (Beck Anxiety Inventory - BAI), Escala Adequação Social (EAS) e Escala de Impressão Clínica Global (CGI). Os grupos experimental e controle foram comparados em três momentos: na triagem, no início e no final das intervenções, utilizando-se análise de variância (ANOVA) para medidas repetidas. Ambos os grupos apresentaram melhora significativa dos sintomas de TTM e depressão ao longo do tratamento (p < 0,001). Sintomas ansiosos e ajustamento social não apresentaram variação significativa. O grupo experimental mostrou uma redução significativamente maior dos sintomas de TTM em comparação com o grupo controle (p=0,038) ao fim do tratamento. Conclui-se que a TCC-G é um método válido para o tratamento da TTM. Revisões futuras e ampliações deste modelo devem ser realizadas para que esse possa abarcar de forma mais eficaz a sintomatologia concorrente, em especial, ansiedade, e o ajustamento social / Trichotillomania (TTM) is a prevalent, disabling disorder, characterized by repetitive hair pulling, which is now included in the obsessive-compulsive and related disorders chapter of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition, DSM-V). There is now evidence that TTM is more common than previously believed, and various treatments have been proposed. Behavioral studies in TTM patients have focused on their maintaining factors. However, it is possible that variables related to cognition, as well as those related to behavior, play a role in etiology and maintenance of TTM. With the exception of three studies of habit reversal therapy, there have been no controlled studies of cognitive-behavioral therapy (CBT) in TTM. The present study aimed to investigate the effectiveness of manual-based group CBT (GCBT), in comparison with that of supportive group therapy (SGT), in 44 patients diagnosed with TTM according to DSM-IV criteria. Patients were randomly allocated to receive 22 sessions of manual-based GCBT (n=22) or SGT (n=22). The main outcome variable was the Massachusetts General Hospital - Hairpulling Scale score. Secondary outcome variables were the Beck Depression and Anxiety Inventory scores, as well as the Social Adjustment Scale-Self-Report score and the Clinical Global Impression score. Using analysis of variance for repeated measures, we compared the two groups at three time points: at the initial screening; at treatment initiation; and at the end of treatment. After treatment, both groups showed significant improvement in symptoms of TTM and depression (p < 0.001), although there were no significant differences in terms of social adjustment or symptoms of anxiety. The improvement in TTM symptoms was more pronounced in the GCBT group than in the SGT group (p=0.038). We conclude that GCBT is a valid method for the treatment of TTM. However, the GCBT treatment model should be revised and expanded in order to treat TTM comorbidities, especially anxiety and social dysfunction, more effectively

INTRODUÇÃO: A despeito das graves consequências comportamentais de indivíduos que sofrem de impulso sexual excessivo (ISE), estudos neuropsicológicos são incipientes e trazem resultados controversos. OBJETIVOS: Por meio de um estudo experimental com sujeitos impulsivos sexuais (pacientes) e não impulsivos sexuais (controles) objetivou-se comparar: a tomada de decisão e a flexibilidade cognitiva no estado basal de vigília (tempo \"0\"); a tomada de decisão e flexibilidade cognitiva no tempo \"0\" e pós-estímulo sexual visual (tempo \"1\") em cada grupo (pacientes e controles) e entre os grupos. MÉTODO: O estudo foi desenvolvido no Ambulatório de ISE do Instituto de Psiquiatria (IPq) do HC-FMUSP. A amostra foi constituída por 30 pacientes e 30 controles recrutados através de divulgação na mídia. Homens, brasileiros, com 18 anos ou mais, que preencheram os critérios diagnósticos para ISE (CID-10 - F 52.7) e os critérios de Goodman para dependência de sexo foram incluídos como pacientes; enquanto participantes assintomáticos e que não preencheram os critérios acima foram incluídos como controles. A investigação neuropsicológica da flexibilidade cognitiva se deu por meio da aplicação Wisconsin Card Sort Test (WCST), enquanto a avaliação da tomada de decisão se deu pela aplicação do Iowa Gambling Task (IGT) no tempo \"0\" e tempo \"1\" (após visualização de vídeo erótico por 20 minutos), respeitando um intervalo mínimo de seis meses entre os tempos. Em ambos os tempos foi aplicada a Escala de Compulsividade Sexual, e no tempo \"1\" foi aplicado o Inventário do Desejo e da Excitação Sexual. RESULTADOS: No estado basal, os pacientes apresentaram maior quantidade de respostas corretas, em relação aos controles, no teste que investiga flexibilidade cognitiva (p = 0,01). Quando comparamos o desempenho de ambos os grupos com eles mesmos entre os tempos, observamos que os controles apresentaram melhor desempenho inicial (Bloco 1) na tomada de decisão (p = 0,01), bem como apresentaram mais acertos no teste que avalia flexibilidade cognitiva (p = 0,01) no tempo \"1\". O mesmo não foi observado em relação aos pacientes. Quando comparamos as médias da diferença (tempo \"1\" - tempo \"0\"), entre os grupos, observamos também melhor desempenho dos controles em relação à quantidade de acertos (p = 0,02). CONCLUSÕES: Desde onde sabemos, este é o primeiro estudo avaliando funções executivas em impulsivos sexuais, após exposição a estímulo visual sexual. Quanto à avaliação no estado basal, os pacientes apresentaram melhores resultados na flexibilidade cognitiva, contrariando a hipótese inicial. Controles apresentaram melhores desempenhos na flexibilidade cognitiva e tomada de decisão inicial após exposição ao estímulo visual sexual, quando comparados com os resultados no estado basal. Na análise da diferença de desempenho pós-estímulo visual sexual comparado com o estado basal, entre os grupos, os controles novamente apresentaram melhor desempenho cognitivo. Tais resultados indicam escolhas iniciais menos impulsivas, e melhor flexibilidade cognitiva, após exposição ao estímulo erótico, pelos controles, sugerindo dificuldades de modulação inicial do comportamento, bem como de funções cognitivas, pelos pacientes, diante do estímulo sexual, apoiando nossas hipóteses / INTRODUCTION: Despite the serious behavioral consequences of individuals suffering from excessive sexual drive (ESD), neuropsychological studies are incipient and bring controversial results. OBJECTIVES: Through an experimental study of sexually impulsive subjects (patients) and non-sexually impulsive (control group) our aim was to compare: decision making and cognitive flexibility during basal wakefulness (Time \"0\"); decision making and cognitive flexibility at time \"0\" and after visual sexual stimulation (time \"1\") in each group (patients and control group) and among groups. METHOD: The study was developed at the ESD Clinic of the Psychiatry Institute (IPq), HC-FMUSP. The sample consisted of 30 patients and 30 people in the control group recruited through media coverage. Brazilian men, 18 years and older who met the diagnostic criteria for ISE (ICD - 10 - 52.7 F) and the Goodman criteria for addiction to sex were included as patients; while asymptomatic participants and that did not meet the above criteria were included in the control group. The neuropsychological research of the cognitive flexibility was made by applying the Wisconsin Card Sort Test (WCST), while the evaluation of the decision-making was made through the application of the Iowa Gambling Task (IGT) at time \"0\" and time \"1\" (after viewing an erotic video for 20 minutes), subject to a minimum interval of six months between times. In both times, the Sexual Compulsivity Scale was applied and to time \"1\", we applied the Sexual Arousal and Desire Inventory. RESULTS: During basal wakefulness patients presented a higher number of correct responses compared to the control group, in the test that investigates cognitive flexibility (p = 0.01). When comparing the performance of both groups to each other in between times, we found that the control group had a better initial performance (Block 1) in decision making (p = 0.01) as well as provided more correct answers in the test that evaluates cognitive flexibility (p = 0.01) at time \"1\". The same was not observed in the patients group. When comparing the average of the difference (time \"1\" - time \"0\") between the groups, we noted a better performance in the control group in what concerns the amount of correct responses (p = 0.02). CONCLUSION: As far as we know, this is the first study assessing executive functions in sexual impulsive, after exposure to sexual visual stimuli. As for the evaluation at basal wakefulness, patients presented better results regarding cognitive flexibility, opposite to the initial hypothesis. The control group presented a better performance concerning cognitive flexibility and initial decision making after exposure to sexual visual stimuli, when compared with results during basal wakefulness. When analyzing the performance difference after visual sexual stimulation compared with basal wakefulness in the two groups, the control group, once again, showed better cognitive performance. Such results indicate less impulsive initial choices and better cognitive flexibility after exposure to erotic stimulation in the control group, suggesting difficulties in the initial modulation of behavior, as well ass of cognitive functions, by patients before sexual stimulation, supporting our hypothesis

O jogo patológico é classificado como um transtorno do controle dos impulsos, que envolve a fissura e a impulsividade para jogar, causando prejuízos sociais. Estudos prévios sugeriram que o topiramato poderia ser mais eficaz do que o placebo no tratamento de alguns transtornos relacionados com impulsividade, tais como transtorno de compulsão alimentar periódico, alcoolismo e dependência de cocaína. O principal objetivo deste estudo foi verificar se o topiramato foi superior ao placebo em controlar fissura e reduzir pensamentos e comportamentos relacionados ao jogo. Método: os jogadores patológicos foram aleatoriamente distribuídos em um de dois grupos: o que recebeu topiramato (n=15) e o que recebeu placebo (n=15) por 12 semanas. Durante o estudo, todos os pacientes participaram de quatro sessões psicoeducacionais, baseadas no programa de 12 passos dos jogadores anônimos. A principal variável de desfecho foi a escala G-SAS. As demais variáveis de desfecho foram consideradas secuindárias, sendo as escalas/entrevista: Escala Yale Brown de obsessão e compulsão adaptada para jogo patológico (PG-YBOCS), Timeline Follow-Back (TFB), questionário de crença de jogadores (GBQ), escala de impulsividade de Barratt (BIS-11), escala de impressão clínica global (CGI), escala de adequação social (EAS). Nos resultados, os pacientes que receberam topiramato obtiveram melhora nos escores das escalas: G-SAS, o que implica em redução dos sintomas de fissura e abstinência; PG-YBOCS, que mostrou redução de comportamentos e obsessões relacionados ao jogo; GBQ, que demonstrou redução de crenças supersticiosas e melhora cognitiva e EAS, que mostrou melhora na qualidade de vida. A entrevista TFB mostrou maiores reduções na média de tempo e quantia de dinheiro gasto em jogo no grupo topiramato em relação ao grupo placebo. Conclusão: o uso de topiramato associado a quatro sessões psicoeducacionais foi superior ao uso de placebo associado a quatro sessões psicoeducacionais, na redução de fissura, freqüência, comportamentos, superstições, quantidade de tempo e dinheiro destinados ao jogo, com melhora na qualidade de vida / Pathological gambling is an impulse control disorder that involves craving and impulsivity to gamble and in which gambling thoughts and behaviors may cause social impairment. Previous studies suggested that topiramate could be effective in the treatment of some disorders related to impulsivity, such as binge eating disorder, alcoholism or cocaine addiction. The studys main goal was to verify if topiramate was superior to placebo in controlling craving and reducing thoughts and behaviors related to gambling. Methods: pathological gamblers were randomized to topiramate (n=15) or placebo (n=15) in a 12-week, double-blind placebo controlled trial. During the 12 weeks the patients had four sessions of a program based on the 12 steps of Anonymous Gamblers. The primary outcome measure was the Gambling Symptom Assessment Scale (G-SAS), which evaluates symptoms related to abstinence. As secondary outcome measures it was used the following scales or interviews: Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS), Timeline Follow-Back Method (TFB), Gamblers Beliefs Questionnaire (GBQ), Barratt Impulsiveness Scale (BIS-11), Clinical Global Impression (CGI), Social Adjustment Scale (SAS). Results: There were statistic robust findings in some of the scales used in this study. The group of patients who took topiramate had improvement in the scores of the G-SAS, which implies reduction in the symptoms of craving and abstinence; PG-YBOCS, which showed reductions in the behaviors and obsessions related to gambling; GBG, which revealed reduction of superstitious thoughts and cognitive improvement, and EAS that showed improvement in the quality of life. TFB showed that the topiramate group had more reductions in the average of time and money spent on gambling than the placebo group. Conclusions: According to the results, topiramate associated with four sessions based in cognitive restructuring were superior to placebo associated with four sessions based in cognitive restructuring in reducing craving, frequency, behaviors and superstitions related to gambling, and amount of time and money used in gambling. Moreover, according to SAS, the group that took topiramate had better improvement in the quality of life than the placebo group

Mon projet de thèse porte sur les altérations de la réponse dopaminergique dans la maladie de Parkinson (MP). Les troubles moteur de la MP sont améliorés par la L-Dopa (précurseur de la dopamine) et/ou les agonistes dopaminergiques. Cependant, ces traitements engendrent des effets secondaires moteurs (les dyskinésies) et non-moteurs. Ainsi, environ 15% des patients atteints de la MP sous agoniste dopaminergique vont présenter des addictions comportementales avec un syndrome de sevrage, et 3 à 4% des patients traités à la L-Dopa ou à l’apomorphine développent une prise compulsive de médicament. Ces complications motrices et non-motrices des thérapies dopaminergiques, font intervenir une dysfonction du réseau des ganglions de la base. Ce travail a exploré le lien entre l’accumulation de la protéine ΔFosB et les modifications des propriétés électriques des neurones impliqués dans l’expression des dyskinésies, en utilisant une technique d’inactivation sélective des neurones exprimant ΔFosB dans le striatum de rat et de singe. Mes travaux ont également évalué chez le singe, comment la L-Dopa modifiait les taux de monoamines pour engendrer les dyskinésies. Ceci m’a permis de montrer que les structures cognitives et limbiques sont elles aussi affectées et qu’elles pourraient être directement impliqués dans les dyskinésies. Sur cette base, j’ai étudié la physiopathologie des troubles du traitement de la récompense et démontré que la L-Dopa, le traitement de référence de la MP, peut acquérir des propriétés récompensantes proches de celles de la cocaïne dans un modèle rat de la MP par surexpression de gène codant pour l’α-synucléine mutée. J’ai également utilisé des procédures d’auto-administration intraveineuse chez le rat pour montrer que le Pramipexole, un agoniste dopaminergique couramment utilisé dans le traitement de la MP, possédait des propriétés renforçantes. Ceci m’a permis de souligner que des susceptibilités individuelles sous-tendraient le développement de ces addictions comportementales. Ces découvertes ont ensuite été complétées par des expériences montrant que les altérations liées à la MP modifiaient le trait d’impulsivité des rats et que les traitements dopaminergiques pouvaient empirer ces changements. / My PhD focused on the alterations of the dopaminergic response in Parkinson’s disease (PD). Motor impairments in PD are reduced by the dopamine precursor L-Dopa and/or dopamine agonists. However, these medications elicit motor (dyskinesia) and non-motor side-effects. Up to 15% of PD patients under dopamine agonists experience behavioral addictions and withdrawal syndrome, and 3-4% of patients treated with L-Dopa or apomorphine exhibit compulsive medication intake. Both motor and non-motor complications of dopaminergic therapies involve dysfunctions in the basal ganglia network. I explored the link between deltaFosB protein accumulation and the cellular electrical properties that trigger dyskinesia by using a cell-type specific inactivation of FosB expressing neurons of the striatum in rats and monkeys. I have also investigated in monkeys how L-Dopa modifies monoaminergic functions to mediate dyskinesia and demonstrated that limbic/cognitive structures are identically affected providing a basis for a non-motor component involved in motor side effects in PD. From this, I studied the pathophysiology of addiction-like disorders by revealing that L-Dopa, the most widely-used treatment for PD, can acquire rewarding properties similar to cocaine in a viral-mediated rat model of PD. I also used self-administration procedures in rats to demonstrate the rewarding properties of Pramipexole, a dopamine agonist commonly use in the treatment of PD, and identified individual susceptibilities in the development of addiction-like disorders. These findings were followed by additional work showing that PD alterations modify the impulsivity trait of rats and that medication might worsen these changes.

ContexteAu cours de la maladie de Parkinson, les agonistes dopaminergiques sont associés à la survenue de troubles du contrôle des impulsions (TCI). Leur physiopathologie est supposée liée à une dérégulation du circuit dopaminergique méso-limbique, impliqué dans l’intégration des conséquences d’une action afin d’adapter les comportements ultérieurs. Les agonistes dopaminergiques, par la stimulation tonique qu’ils entrainent, conduiraient à une surestimation des conséquences positives des actions antérieures et la poursuite de comportements aux conséquences néfastes.Nous avons exploré (i) la connectivité fonctionnelle striato-corticale en IRM fonctionnelle de repos, (ii) des marqueurs électro-encéphalographiques (EEG) d’intégration du feedback au cours d’une tache de pari : feedback-related negativity (FRN), feedback-related positivity (FRP) et oscillations dans la bande de fréquence thêta (4-7 Hz) chez 20 patients parkinsoniens avec TCI actif, 19 patients parkinsoniens sans TCI et 19 contrôles sains.IRM fonctionnelle : Le striatum ventral, le noyau caudé dorsal, le putamen antérieur et postérieur étaient segmentés semi-automatiquement. Pour chaque région d’intérêt, une analyse de connectivité fonctionnelle était réalisée sur les données d’IRM fonctionnelle projetées sur la surface corticale.Approche neurophysiologique : les sujets réalisaient une tâche composée de paris répétés, couplée à un enregistrement EEG. Le signal EEG était moyenné pour chaque condition et pour chaque sujet. L’amplitude de la FRP était mesurée en Cz et l’amplitude de la FRN en Fz sur la courbe de différence entre les potentiels évoqués par les pertes et les potentiels évoqués par les gains. Les spectres de puissance ont été calculés en utilisant une transformation en ondelettes sinusoïdales de Morlet et moyennés par condition. La puissance maximale du signal, dans la bande de fréquence thêta, entre 200 et 500 millisecondes après l’affichage du feedback était mesurée.Analyse de la connectivité striato-corticale : Chez les patients parkinsoniens, l’existence d’un TCI était associée à une déconnexion fonctionnelle entre le putamen antérieur gauche et les gyrus cingulaire antérieur et temporal inférieur gauche. Il existait chez ces patients une tendance à une déconnexion fonctionnelle entre (i) le putamen antérieur gauche et le gyrus frontal inférieur, (ii) le putamen postérieur et les gyrus temporal inférieur, frontal supérieur, cingulaire postérieur et frontal médial à gauche, ainsi que les gyrus frontal médial, cingulaire et frontal moyen à droite, (iii), le noyau caudé dorsal et le gyrus rectus, le gyrus frontal moyen et le gyrus temporal inférieur à gauche.Potentiels évoqués : Chez les patients parkinsoniens sans TCI et chez les contrôles, mais pas chez les patients parkinsoniens avec TCI, la FRP était plus ample après les gains qu’après les pertes suite à un choix peu risqué.Analyse temps-fréquence : En Cz, les gains étaient associés à une augmentation plus importante de la puissance thêta que les pertes chez les patients parkinsoniens sans TCI et chez les contrôles, mais pas chez les patients parkinsoniens avec TCI. Il existait une augmentation de la puissance thêta après un résultat ample inattendu (boost), en Fz chez les contrôles et en FCz chez les parkinsoniens avec TCI, mais pas chez les patients parkinsoniens sans TCI.Il existe chez les patients parkinsoniens ayant un TCI une altération de marqueurs EEG d’intégration de la récompense compatible avec une moins bonne discrimination des gains et des pertes et une plus grande sensibilité aux résultats amples, inattendus (boost), supposés entrainer une activation importante des voies dopaminergiques méso-limbiques. Il semble donc bien exister, chez les patients ayant un TCI une dysfonction des mécanismes d’intégration du feedback. Cette dysfonction s’associe, au repos, à une altération de la connectivité striato-corticale qui va au-delà du seul système limbique. / BackgroundIn Parkinson’s disease, dopamine agonists are associated with an increased risk of impulse control disorders (ICD). Their occurrence is supposed to be related with a deregulation of the dopaminergic meso-limbic pathway, involved in the processing of the consequences of previous action to adapt future behaviors. Dopamine agonists, through a tonic stimulation of the dopamine receptors would lead to an overestimation of the positive consequences of actions, and therefore, continuation of a harmful behavior.Method:We investigated (i) the resting-state striato-cortical functional connectivity using functional MRI, and (ii) electro-encephalographic (EEG) markers of feedback processing during a gambling task : the feedback related negativity (FRN), the feedback related positivity, (FRP), and the theta band oscillations (4-7 Hz) in 20 Parkinson’s disease patients with an active ICD, 19 Parkinson’s disease patients without ICD, and 19 healthy subjects.Functional MRI: The ventral striatum, dorsal caudate, and anterior and posterior putamen were semi-automatically segmented. For each region of interest, a seed-based connectivity analysis was performed on preprocessed fMRI data mapped on the ipsilateral cortical surface.Neurophysiological approach: The subjects underwent an EEG while performing a gambling task. The EEG was averaged for each condition and each subject. The FRP amplitude was measured in Cz, and the FRN amplitude was measured in Fz on the difference wave between the potential evoked by losses and by gains. The power spectra were computed by using a sinusoidal Morlet wavelet transform and averaged by condition. The maximum power in the theta frequency band was computed for each participant and each condition.Results:Cortico-striatal connectivity analysis: The presence of an ICD in patients with PD was associated with functional disconnection between the left anterior putamen and both the left inferior temporal and anterior cingulate gyrus. ICD patients also displayed a trend toward a functional disconnection between (i) the left anterior putamen and the inferior frontal gyrus, (ii) the posterior putamen and the inferior temporal gyrus, superior frontal gyrus, posterior cingulate, and medial frontal gyrus on the left, as well as the medial frontal gyrus, middle frontal gyrus, and cingulate gyrus on the right, (iii) the dorsal caudate and the gyrus rectus and orbitofrontal cortex, and the middle frontal and inferior temporal gyrus on the left.Evoked potentials: In Parkinson’s disease patients without ICD and healthy controls, the FRP was greater after gains that after losses following a non-risky choice. There was no difference in FRP amplitude after losses and gains in Parkinson’s disease patients with ICD.Time-frequency analysis: At Cz, positive outcomes (gains) were associated with greater theta power than negative outcomes (losses) in Parkinson’s disease patients without ICD and in healthy controls, but not in Parkinson’s disease patients with ICD. There was an increase in theta power after unexpectedly high outcomes, at Fz in healthy controls and in FCz in Parkinson’s disease patients with ICD, whereas theta power was not modulated by the magnitude of the outcome in PD patients without ICDs.Conclusions:Parkinson’s disease patients with ICD have an alteration in EEG markers of reward in line with an altered discrimination of gains and losses and a greater sensitivity to unexpectedly high outcomes, supposed to lead to a significant activation in the dopaminergic meso-limbic pathways. These findings are in line with a dysfunction in reward processing in ICD in Parkinson’s disease. This dysfunction is associated, at rest, with an alteration in striato-cortical connectivity that goes beyond a pure dopaminergic meso-limbic dysfunction.

In der vorliegenden Studie wurde mittels der Bildgebung des funktionellen MRT die Dynamik der neuronalen Hirnmechanismen untersucht, die es dem Menschen erlauben, durch kurzfristigen Verzicht auf Belohnungen seinen Verhaltenserfolg langfristig zu optimieren. Durch den Vergleich zweier Extremgruppen gesunder Probanden (hoch- versus niedrig- impulsive Probanden) sollte ein möglicher Zusammenhang zwischen der Impulsivität und dem funktionellen Zusammenspiel frontostriataler Regelkreise während des aktiven Prozesses der Entscheidungsfindung dargestellt werden. Die vorliegende Studie hat gezeigt, dass gesunde, nicht- klinische Individuen, die sich selbst mittels der Barratt- Impulsivitätsskala als hoch- impulsiv charakterisiert haben, ihr Verlangen nach einer direkten Belohnung erfolgreich durch Aktivierung zweier komplementärer Hirnmechanismen kontrollieren können. Als erster Mechanismus ist festzuhalten, dass selbstkontrollierte Entscheidungen zu einer Abschwächung der belohnungsabhängigen Aktivierung im Nucleus accumbens führten, welche von einer ansteigenden inversen Verbindung mit dem anteroventralen präfrontalen Kortex begleitet wurde. Der zweite Mechanismus ist, dass HI- Probanden ihren Wunsch nach einer höherwertigen, aber suboptimalen Belohnung in Abhängigkeit von der Wertigkeit der unmittelbaren Belohnung durch Downregulation im ventromedialen präfrontalen Kortex kontrollierten. Diesem Mechanismus folgte eine ansteigende inverse Kopplung mit dem ventralen Striatum. Von entscheidender Bedeutung ist dabei, dass sich diese neuronalen Mechanismen qualitativ von denen der extrem- kontrollierten Probanden unterschieden. Insgesamt lässt sich sagen, dass diese Ergebnisse darauf hindeuten, dass es persönlichkeitsspezifische neuronale Mechanismen gibt, die es hoch-impulsiven Probanden ermöglichen, ihren Wunsch nach einer unmittelbaren Belohnung zu kontrollieren.

O jogo patológico é classificado como um transtorno do controle dos impulsos, que envolve a fissura e a impulsividade para jogar, causando prejuízos sociais. Estudos prévios sugeriram que o topiramato poderia ser mais eficaz do que o placebo no tratamento de alguns transtornos relacionados com impulsividade, tais como transtorno de compulsão alimentar periódico, alcoolismo e dependência de cocaína. O principal objetivo deste estudo foi verificar se o topiramato foi superior ao placebo em controlar fissura e reduzir pensamentos e comportamentos relacionados ao jogo. Método: os jogadores patológicos foram aleatoriamente distribuídos em um de dois grupos: o que recebeu topiramato (n=15) e o que recebeu placebo (n=15) por 12 semanas. Durante o estudo, todos os pacientes participaram de quatro sessões psicoeducacionais, baseadas no programa de 12 passos dos jogadores anônimos. A principal variável de desfecho foi a escala G-SAS. As demais variáveis de desfecho foram consideradas secuindárias, sendo as escalas/entrevista: Escala Yale Brown de obsessão e compulsão adaptada para jogo patológico (PG-YBOCS), Timeline Follow-Back (TFB), questionário de crença de jogadores (GBQ), escala de impulsividade de Barratt (BIS-11), escala de impressão clínica global (CGI), escala de adequação social (EAS). Nos resultados, os pacientes que receberam topiramato obtiveram melhora nos escores das escalas: G-SAS, o que implica em redução dos sintomas de fissura e abstinência; PG-YBOCS, que mostrou redução de comportamentos e obsessões relacionados ao jogo; GBQ, que demonstrou redução de crenças supersticiosas e melhora cognitiva e EAS, que mostrou melhora na qualidade de vida. A entrevista TFB mostrou maiores reduções na média de tempo e quantia de dinheiro gasto em jogo no grupo topiramato em relação ao grupo placebo. Conclusão: o uso de topiramato associado a quatro sessões psicoeducacionais foi superior ao uso de placebo associado a quatro sessões psicoeducacionais, na redução de fissura, freqüência, comportamentos, superstições, quantidade de tempo e dinheiro destinados ao jogo, com melhora na qualidade de vida / Pathological gambling is an impulse control disorder that involves craving and impulsivity to gamble and in which gambling thoughts and behaviors may cause social impairment. Previous studies suggested that topiramate could be effective in the treatment of some disorders related to impulsivity, such as binge eating disorder, alcoholism or cocaine addiction. The studys main goal was to verify if topiramate was superior to placebo in controlling craving and reducing thoughts and behaviors related to gambling. Methods: pathological gamblers were randomized to topiramate (n=15) or placebo (n=15) in a 12-week, double-blind placebo controlled trial. During the 12 weeks the patients had four sessions of a program based on the 12 steps of Anonymous Gamblers. The primary outcome measure was the Gambling Symptom Assessment Scale (G-SAS), which evaluates symptoms related to abstinence. As secondary outcome measures it was used the following scales or interviews: Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS), Timeline Follow-Back Method (TFB), Gamblers Beliefs Questionnaire (GBQ), Barratt Impulsiveness Scale (BIS-11), Clinical Global Impression (CGI), Social Adjustment Scale (SAS). Results: There were statistic robust findings in some of the scales used in this study. The group of patients who took topiramate had improvement in the scores of the G-SAS, which implies reduction in the symptoms of craving and abstinence; PG-YBOCS, which showed reductions in the behaviors and obsessions related to gambling; GBG, which revealed reduction of superstitious thoughts and cognitive improvement, and EAS that showed improvement in the quality of life. TFB showed that the topiramate group had more reductions in the average of time and money spent on gambling than the placebo group. Conclusions: According to the results, topiramate associated with four sessions based in cognitive restructuring were superior to placebo associated with four sessions based in cognitive restructuring in reducing craving, frequency, behaviors and superstitions related to gambling, and amount of time and money used in gambling. Moreover, according to SAS, the group that took topiramate had better improvement in the quality of life than the placebo group