Introdução: A automutilação é definida como qualquer comportamento intencional envolvendo agressão direta ao próprio corpo sem intenção consciente de suicídio. As formas mais frequentes de automutilação são cortar a própria pele, queimar-se, bater em si mesmo, morder-se e arranharse. Alguns pacientes apresentam rituais de automutilação e passam muito tempo pensando em como executá-la, lembrando sintomas compulsivos, porém com intenso componente de impulsividade. O DSM-IV classifica a automutilação como um dos critérios de diagnósticos para transtornos do controle dos impulsos não classificados em outro local ou Transtorno de Personalidade Borderline. O DSM-V propõe que a automutilação seja uma entidade diagnóstica à parte. A falta de homogeneidade na descrição da automutilação dificulta as pesquisas, tanto epidemiológicas como clínicas. A melhor caracterização clínica e psicopatológica da automutilação é fundamental para que intervenções terapêuticas mais efetivas possam ser desenvolvidas, incluindo novas abordagens psicofarmacológicas. Os objetivos deste estudo foram: fazer uma descrição clínica dos pacientes que procuram tratamento, tendo como principal queixa a automutilação e comparar estes com pacientes com Transtorno Obsessivo-Compulsivo (TOC) quanto a características compulsivas e impulsivas. Métodos: 70 pacientes foram avaliados, sendo 40 pacientes com automutilação e 30 pacientes com TOC. Todos estes pacientes foram avaliados de forma direta com os instrumentos: Entrevista Clínica Estruturada para Transtornos de Eixo I do DSM-IV, versão clínica (SCID-I); Entrevista Clínica Estruturada para Transtornos de Eixo I do DSM-IV, versão clínica, adaptada para Transtornos de Controle de Impulsos; Entrevista Clínica Estruturada para Transtornos de Eixo II, versão clínica (SCID-II); Escala de Sintomas Obsessivo-Compulsivos de Yale-Brown (Y-BOCS); Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos (DY-BOCS); Escala para Avaliação da Presença e Gravidade de Fenômenos Sensoriais da Universidade de São Paulo (USP-SPS); Questionários de História de Traumas; Escala de Comportamento de Automutilação (FASM); e Barrat Impulsivity Scale (BIS-11). Para comparação das variáveis categóricas, foi utilizado o teste qui-quadrado e para variáveis contínuas, o test-t. Para análise multivariada, foram utilizados os testes ANCOVA ou Regressão Logística Linear. Foi considerado, para todos os testes, o nível de significância 5%. Resultados: A média de idade dos pacientes avaliados foi de 29 anos. Quanto às características clínicas dos pacientes com automutilação, estes iniciaram o comportamento em média aos 17 anos de idade, e apresentavam cinco tipos diferentes de automutilação em média. Os comportamentos mais frequentes foram: cortar a pele (90%), cutucar ferimentos (75%), bater em si mesmo (67,5%). Os motivos mais frequentemente relacionados à automutilação foram para: parar sentimentos ruins (75%), aliviar sensação de vazio (70%), se castigar (70%), sentir algo, mesmo que fosse dor (47,5%) e sentir-se relaxado (40%). Na comparação entre os grupos com automutilação e TOC, quanto às comorbidades do Eixo I, o grupo com automutilação apresentou mais comorbidades com depressão (92,5%, p=0,03) e bulimia (25%, p<0,001). O grupo com TOC apresentou mais fobia social (40%, p<0,001). Os pacientes do grupo com TOC tiveram maior gravidade em todas as medidas do Y-BOCS (média: 26, p<0,001) e DY-BOCS (média 23,1, p=0,01). No grupo com automutilação, 60% dos pacientes referiram a automutilação associada a fenômenos sensoriais. Este grupo teve mais relato de fenômenos sensoriais referente à \"sensação de incompletude\" (45%, p=0,007) e \"sensação de energia interna\" (57,5%, p=0,001). O transtorno de personalidade mais prevalente em ambos os grupos foi Transtorno de Personalidade Obsessivo-Compulsiva. O grupo com automutilação apresentou maior prevalência de Transtorno de Personalidade Histriônica (22,5 %, p=0,02) e Transtorno de Personalidade Borderline (15%, p=0,04). A gravidade da impulsividade foi maior no grupo com automutilação segundo as medidas da BIS-11 para características motoras (média 26,6, p=0,002) e dificuldade para planejamento (média 31, p=0,014). Conclusão: A automutilação e o TOC são transtornos heterogêneos que compartilham características compulsivas e impulsivas. Na automutilação, o componente impulsivo é maior e no TOC, a compulsividade é maior quando comparamos estes dois grupos. Entretanto, a automutilação esteve associada à ocorrência de fenômenos sensoriais, apontando também para a presença de aspectos compulsivos nestes quadros. O Transtorno de Personalidade Borderline não é regra entre os pacientes com automutilação. Outros transtornos de personalidade, inclusive cluster C como o Transtorno de Personalidade Obsessivo-Compulsiva, também podem estar presentes entre pacientes com automutilação, assim como com TOC. Os pacientes adultos com automutilação apresentam este comportamento desde a adolescência e os tipos de automutilação apresentados por estes são de moderada a grave intensidade, além de associarem diferentes tipos de automutilação. Isto evidencia a necessidade de desenvolvimento de instrumentos diagnósticos mais precisos para identificação e tratamento precoce específico para estes quadros, evitando a cronicidade dos mesmos / Introduction: Non-suicidal self-injury (NSSI) is defined as a deliberate and voluntary physical self-injury without any conscious suicidal intent. Common forms of NSSI include cutting, burning, scratching, hitting, biting and interfering with wound healing. Some patients spend a lot of time thinking about how to perform their act doing it always the same way. They remember compulsive symptoms with intense component of impulsivity. The DSM-IV classifies NSSI as one diagnostic criteria for impulsive control disorders not elsewhere classified or as borderline personality disorder. The DSM-V proposes that the NSSI should be classified as a different disorder. The lack of a singular meaning for NSSI makes difficult the clinical and epidemiological researches about the subject. A better clinical and psychopathological definition for NSSI is crucial for the development of more effective therapeutic interventions, including new psychopharmacological treatment. The objective of this study is to describe the clinical features of patients seeking treatment for NSSI and compare their compulsive and impulsive features with patients with Obsessive Compulsive Disorder (OCD). Methods: 70 patients were interviewed, 40 patients who specifically sought treatment for NSSI and 30 patients who sought treatment for OCD. Standardized instruments were used: Structured Clinical Interview for Diagnosis of Axis I, according to DSM-IV and for impulse-control disorders, Structured Clinical Interview for Axis II Disorders (Clinical Version (SCID-II)), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS); Dimensional Yale- Brown Obsessive-Compulsive Scale (DY-BOCS), University of São Paulo Sensory Phenomena Scale (USP-SPS); Trauma History Questionnaire; Functional Assessment of Self-Mutilation (FASM) and Barratt Impulsivity Scale, version-11 (BIS -11). To compare categorical variables the chi-square test was applied. For continuous variables, t-test was applied. For multivariate analysis, the ANCOVA test or Logistic Regression were applied when required. A significance level of 5% was applied for all statistical tests. Results: The mean age of patients was 29 years. The NSSI began at 17 years old, and had 5 different types of NSSI on average. The more common behaviors were: cutting the skin (90%), pick at a wound (75%), beat himself (67.5%). The most often reasons for NSSI were to: stop bad feelings (75%), relieve feeling numb or empty (70%), punish himself (70%), feel something, even if it was pain (47.5%) and feel relaxed (40%). In the comparison between NSSI and OCD groups, the NSSI group presented more axis I comorbidities with depression (92.5%, p = 0.03) and bulimia (25%, p <0.001). The OCD group showed more social phobia (40%, p <0.001). The OCD group had higher severity in all measures of the Y-BOCS (mean: 26, p <0.001) and DY-BOCS (mean 23.1, p = 0.01). In the NSSI group, 60% of the patients reported NSSI associated with sensory phenomena. This group had more reports of sensory phenomena related to the \"incompleteness\" (45%, p = 0.007) and \"internal energy\" (57.5%, p = 0.001). The most prevalent personality disorder in both groups was Obsessive-Compulsive Personality Disorder. The NSSI group had higher prevalence of Histrionic Personality Disorder (22.5%, p = 0.02) and Borderline Personality Disorder (15%, p = 0.04). The severity of impulsivity was higher in the NSSI group according to the measures of the BIS-11 for motor impulsivity (mean 26.6, p = 0.002) and non-planning impulsivity (mean 31, p= 0.014). Conclusion: NSSI and OCD are heterogeneous disorders that share compulsive and impulsive features. In NSSI, the impulsive component is stronger and in OCD the compulsive is stronger when comparing both groups. However, NSSI was associated with the occurrence of sensory phenomena which evidence the presence of compulsive aspects. The borderline personality disorder is not a rule among patients with NSSI. Other personality disorders, including cluster C personality disorders, may also be present among patients with NSSI and OCD, as well. Adult patients with NSSI started this behavior during adolescence. The NSSI symptoms presented were moderate to severe, different types of NSSI were also involved. These results highlights the needs for development of more accurate diagnostic tools for early identification and specific treatment of the NSSI, avoiding chronicity

Esta pesquisa parte de uma indicação de Freud, encontrada no caso do Homem dos Ratos, de que a ironia não estaria atrelada às forças compulsivas. Assim, com o objetivo de investigar o uso da ironia nesse tipo específico de neurose, destaca-se inicialmente a necessidade de percorrer as teorizações acerca da neurose obsessiva ao longo da obra freudiana. O percurso demonstra que a renúncia da destrutividade culmina nas defesas sintomáticas obsessivas. Com a segunda tópica, essas formações tornam-se consequências da submissão do Eu à severidade do Supereu. A regressão à fase sádico-anal também passa a ser atribuída à desfusão pulsional e à proeminência da pulsão de morte. De fato, percebe-se que os estudos sobre neurose obsessiva conduzem Freud a um maior entendimento da destrutividade, exigindo reorganizações teóricas nas esferas clínica, metapsicológica e cultural. Deste modo, diante do exposto na primeira parte, o estudo possibilita a tradução do modo de ser obsessivo em uma retórica própria, denominada de retórica anal da reatividade e da supermoralidade. Associa-se a esta retórica figuras de linguagem que visam atenuar, interromper, anular e corrigir desejos, tais como o eufemismo, as reticências, a elipse e a epanortose. Já a presença da negativa (Verneinung) sinaliza uma possibilidade de constatação do recalcado sem aceitação do conteúdo. De posse de uma retórica obsessiva, a segunda parte do estudo compreende a ironia à luz da teoria freudiana. A obra do Witz tem uma relevância particular nesse entendimento ao proporcionar: o único momento em que Freud define ironia; e o primeiro modelo de sublimação em Freud a partir de uma estética da criação verbal. Já a teoria freudiana do humor, juntamente com a obra de Kupermann, contribui para a articulação da sublimação com o campo do trágico. É o caso do humor irônico presente no comentário do condenado à morte: Bem, a semana começa bem!. É evidenciado, assim, o trabalho da desidealização na passagem de uma identificação narcísica para uma identificação sublimatória, o que colabora para a hipótese de uma possível flexibilização identificatória na neurose obsessiva via desidealização (humorística e irônica). Em seguida são analisados dois exemplos de uso da ironia em casos freudianos (O Pequeno Hans e a Jovem Homossexual). A ironia é percebida como ceticismo e vingança à palavra do pai, aproximada ora da denegação, ora do desmentido. Por fim, a última etapa do trabalho dedica-se à exposição das relações entre destrutividade e criação na psicanálise, mais particularmente no tocante à problemática da sublimação das pulsões destrutivas. Portanto, diante das balizas teóricas traçadas, concluise que o uso da ironia na neurose obsessiva compreende quatro tempos: o tempo do inconsciente, onde a palavra é recalcada; o tempo da constatação, onde a palavra é denegada; o tempo transgressor, onde a palavra é sádica; e o tempo do desamparo, onde o uso é criativo e a palavra é sublimada / This research is part of a Freud indication, found in \"The Rat Man\", which tells that irony is not linked to the compulsive forces. So in this sense, aiming at investigating the use of irony in this kind of neurosis, the need to go about the obsessional neurosis theories is a must-do at first, in the course of Freud`s work. This line of thought proves that the destruction resignation leads to the symptomatic obsessive defenses. With the second topography, these formations become a result of the Ego submission to the Super-ego severity. The regression to the anal-sadistic stage is also related to the instinctual defusion and the prominence to death instincts. In fact, we can notice that the studies on obsessive neurosis lead Freud to a wider understanding of destructivity, demanding theoretical reorganizations in the clinical, metapsychological and cultural fields. This way, from what could be gathered, the study enables the translation of the obsessive way of being in a proper rhetoric, named reactivity and super-morality anal rhetoric. This is attached to figures of speech that aim at diminishing, interrupting, blocking and correcting desires, such as euphemism, ellipsis and epanorthosis. As for the presence of negation (Verneinung), this makes it possible to confirm the repressed without a content acceptance. Bearing an obsessive rhetoric, the second part of the study analyzes irony in accordance with Freud`s theory. The Witz work has particular importance in this understanding as it provides: the only moment when Freud defines irony; and the first sublimation moment in Freud starting from the verbal creation aesthetics. As for the Freudian theory of humor, together with Daniel Kupermann`s work, it contributes to the bond between sublimation and the idea of tragedy. That`s the case of ironic humor which shows up in the comments of the sentenced to death: Well, the week starts well!. It`s proved, then, the work of deidealization in the passage of a narcissistic identification to a sublimating identification, what contributes to the hypothesis of a possible identifying flexibilization of obsessive neurosis through deidealization (humorous and ironic). Then, two examples of the use of irony in Freudian cases will be analyzed, The Little Hans and Homosexuality in a Woman. Irony is perceived as skepticism and revenge to the father words, closer sometimes to negation and some other times to denial. At last, the final stage of this job refers to the explanation on the relations between destructivity and creation within psychoanalysis, especially in what refers to the problem of sublimation of destructive instincts. Finally, in light of all the preset theory bases, it could be stated that the use of irony in the obsessional neurosis bears four times: unconscious time, when word is repressed; confirmation time, when word is denied; transgressive time, when word is sadistic; and helplessness, when use is creative and word is sublimated

Vários estudos indicam que o canabidiol (CBD) apresenta grande potencial terapêutico por possuir propriedades anti-inflamatória, analgésica, anticonvulsivante, anticompulsiva, entre outras. No entanto, o CBD apresenta baixa biodisponibilidade, o que pode comprometer seu uso clínico. Além disso, os múltiplos efeitos farmacológicos do CBD ocorrem por diferentes mecanismos. Nesse sentido, o desenvolvimento de compostos com efeitos semelhantes ao CBD, porém mais potentes e/ou com melhor perfil farmacocinético, seria importante. Assim, no presente estudo, nós avaliamos os efeitos induzidos por um derivado fluorado do CBD, o HU-474, comparando-os com aqueles induzidos pelo CBD. Para isso, camundongos suíços machos foram submetidos a modelos animais sensíveis a drogas anticompulsivas (teste de enterrar esferas) e antinociceptivas (teste da placa quente, contorção abdominal e hiperalgesia inflamatória). Para o estudo dos mecanismos envolvidos nos efeitos destes compostos, foram utilizados os antagonistas dos receptores canabinóides CB1, AM251, e CB2, AM630. Adicionalmente, nós avaliamos se o HU-474 induziria os efeitos clássicos (tétrade canabinóide) observados após a administração de agonistas dos receptores CB1 como hipolocomoção, hipotermia, catalepsia e antinocicepção. Os possíveis efeitos antinociceptivos e da tétrade canabinóide induzidos pelo CBD e HU-474 foram comparados com os efeitos induzidos pelo WIN55,212-2, uma agonista dos receptores CB1/2. Foi observado que o CBD (30 e 60mg/kg) e o HU-474 (10mg/kg) induziram uma diminuição no número de esferas enterradas, efeito comparado ao da fluoxetina e atenuado pelos antagonistas AM251 e AM630. Como esperado, o WIN55,212-2 induziu a tétrade canabinóide, um efeito não observado com o CBD e HU-474. No teste da placa quente o HU-474 (30 mg/kg) e WIN55,212-2 (5mg/kg) induziram efeito antinociceptivo. O pré- tratamento com AM251 e AM630 atenuaram os efeitos do HU-474 e WIN55,212-2. No teste de contorção abdominal induzida pelo ácido acético, o CBD (30 e 90 mg/kg), HU-474 (30mg/kg) e WIN55,212-2 (3 e 5mg/kg) induziram efeito antinociceptivo caracterizado pela redução no número de contorções abdominais. O pré-tratamento com AM251 atenuou o efeito apenas do WIN55,212-2, mas não dos outros compostos. Já o antagonista AM630 não foi capaz de atenuar o efeito de nenhum dos compostos testados. No modelo de hiperalgesia inflamatória induzida por carragenina, o CBD (30 e 90mg/kg), HU-474 (3, 10 e 30mg/kg) e WIN55,212-2 (1mg/kg) foram capazes de diminuir a intensidade de hiperalgesia mecânica, avaliada pelo método de von Frey. Sendo que os efeitos do WIN55,212-2, CBD e HU-474 foram atenuados pelo pré-tratamento com AM251 e AM630. Estes resultados indicam que o HU-474 induz efeitos anticompulsivos semelhantes ao CBD, mas em doses mais baixas, através de mecanismo dependente da ativação dos receptores CB1 e CB2. Além disso, o HU-474 apresentou propriedades antinociceptivas em todos os testes utilizados, em doses semelhantes ou menores que o CBD. Os efeitos antinociceptivos dos três compostos testados foram dependentes da ativação de receptores CB1 e CB2, com exceção do teste de contorção abdominal, onde os efeitos do CBD e HU-474 não foram bloqueados por nenhum dos dois antagonistas testados. Diferente do WIN55,212-2, o CBD e HU-474 não induziram tétrade canabinóide. Esses resultados evidenciaram efeitos mais significativos do HU-474, indicando que a adição de um átomo de flúor a molécula de CBD foi capaz de melhorar o seu perfil farmacológico. Além disso, os resultados com o pré-tratamento com os antagonistas AM251 e AM630 nos permitem sugerir um mecanismo misto, visto que há o envolvimento dos receptores CB1 e CB2. Desse modo, esse novo composto poderia ser uma alternativa terapêutica para o tratamento do transtorno obsessivo-compulsivo, bem como dores agudas em doses menores que o CBD / Cannabidiol (CBD) has several therapeutic properties such as antiinflammatory, analgesic, anticonvulsivant and anticompulsive. These multiple pharmacological effects occur by different mechanisms. However, CBD exhibits low bioavailability, which may compromise its clinical use. Thus, the development of CBD analogues, more powerful and/or better pharmacokinetic profile would be interest. Here, we evaluated the effects of a fluorinated derivative of CBD, HU-474, comparing its effects with those induced by CBD. Male Swiss mice were submitted to animal models predictive to anti-compulsive (marble burying test) and antinociceptive drugs (hot plate, abdominal writhing and inflammatory hyperalgesia test). To study the mechanisms involved in their effects were used antagonist of the cannabinoid receptor CB1(AM251) and CB2 (AM630). We also evaluated whether HU-474 would induce the classic effects (cannabinoid tetrad) observed after the administration of CB1 receptors agonists. The cannabinoid tetrad is characterized by hypolocomotion, hypothermia, catalepsy, and antinociception. The possible antinociceptive effects and cannabinoid tetrad induced by CBD and HU-474 were compared with those induced by WIN55,212-2, a CB1/2 receptor agonist. CBD (30 and 60mg/kg), and HU-474 (10mg/kg) decreased the number of buried marble, an effect compared with fluoxetine an attenuated by AM251 and AM630. As expected, WIN55,212-2 induced the cannabinoid tetrad, an effect that was not observed after CBD or HU-474 administration. In the hot plate test, HU-474 (30mg/kg) and WIN55,212-2 (5mg/kg) induced antinociceptive effect. Pretreatment with AM251 and AM640 attenuated the effects induced by HU-474 and WIN55,212-2. In the abdominal writhing test induced by acetic acid, CBD (30 and 90mg/kg), HU-474 (30mg/kg) and WIN55,212-2 (3 and 5mg/kg) induced antinociceptive effects characterized by a reduction in the number of writhing. Pretreatment with AM251 only attenuated the effect of WIN55,212-2, but not of the other compounds, while AM630 didn\"t attenuated the effect of any of the tested compounds. In an inflammatory hyperalgesia model induced by carrageenan, CBD (30 and 90mg/kg), HU-474 (3, 10 and 30mg/kg) and WIN55,212-2 (1mg/kg) decreased the intensity of mechanical hyperalgesia measured by electronic von Frey method. The effects of all compounds were attenuated by the pretreatment with AM251 and AM630. These results indicate that HU-474 exhibits anti-compulsive effects similar to CBD, but at lower doses, through a mechanism dependent of the activation of CB1 and CB2 receptors. Furthermore, HU-474 showed antinociceptive properties in all tests at similar or lower doses than CBD. The antinociceptive effects of the three compounds tested were dependent on the activation of CB1 and CB2 receptors, excepted to the writhing test, where the effects of CBD and HU-474 were not attenuated by any of the two antagonists tested. Moreover, unlike WIN55,212-2, CBD and HU- 474 didn\'t induce cannabinoid tetrad. These results showed more significant effects of HU-474, indicating that the addition of fluoride improved the pharmacological profile of CBD. Furthermore, the results with pretreatment with the antagonist AM251 and AM630 allow us to suggest that these effects involve the activation of CB1 and CB2 receptors. Thus, this new compound could be a therapeutical alternative for the treatment of obsessive-compulsive disorder and acute pain in lower doses than CBD

Métodos: Foi utilizado o SCID-IP para o diagnóstico de esquizofrenia e do TOC. Sessenta pacientes responderam às escalas DY-BOCS, Y-BOCS, PANSS e CGI. Os testes Qui-quadrado com correção de Yates, Mann-Whitney U e Kruskal-Wallis foram usados na análise estatística. Resultados: Dentre os sessenta pacientes avaliados, dez (16,7%) apresentavam critérios diagnósticos pelo DSM-IV para esquizofrenia e TOC; treze (21,7%) tinham SOC, mas não TOC e trinta e sete (61,6%) não tinham TOC ou SOC. A prevalência de TOC ou SOC foi semelhante em pacientes tomando clozapina ou haloperidol (40% VS 35%, respectivamente). Contudo, pacientes tomando clozapina apresentaram maior gravidade dos SOC quando comparados aos pacientes tomando haloperidol. (P= 0.027). Pacientes com esquizofrenia e TOC apresentaram maior gravidade dos sintomas da esquizofrenia quando comparados aos pacientes com esquizofrenia sem SOC (P= 0.002). Conclusões: Apesar da presença de SOC ou TOC ter sido semelhante entre os grupos tomando clozapina ou haloperidol, pacientes em uso de clozapina apresentaram escores mais elevados na YBOCS. Estes resultados podem sugerir uma associação entre a exacerbação do fenômeno obsessivo-compulsivo e o uso de clozapina. Pacientes com esquizofrenia e TOC apresentaram uma maior gravidade dos sintomas da esquizofrenia comparativamente aos demais grupos / Objective: We conducted a cross-sectional study to compare the prevalence and severity of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) in patients with schizophrenia treated with clozapine or haloperidol. Methods: SCID-I/P was used for the diagnoses of schizophrenia and OCD. Sixty subjects completed Y-BOCS, PANSS and CGI scales. Chi-square with Yates correction, Mann-Whitney U and Kruskal-Wallis tests were used for the statistical analyses. Results: Among the sixty schizophrenia patients evaluated, ten (16,7 %) met DSM-IV criteria for both schizophrenia and OCD; thirteen (21,7 %) had OCS but not OCD and thirty-seven (61,6 %) had neither OCD nor OCS. The prevalence of OCD or OCS was similar in patients taking clozapine or haloperidol (40% vs 35%, respectively). However, patients using clozapine showed higher severity of OCS than patients using haloperidol (P= 0,027). Patients with schizophrenia and OCD also showed higher severity of schizophrenic symptoms when compared to patients with schizophrenia without OCS (P= 0,002). Conclusions: Although the presence of OCS or OCD was similar between the groups taking clozapine or haloperidol, patients using clozapine showed higher scores in the YBOCS. These results may support an association between the exacerbation of obsessive-compulsive phenomena and the use of clozapine. Patients with schizophrenia and OCD showed a higher severity on psychotic symptoms than the other groups

Vários estudos indicam que o canabidiol (CBD) apresenta grande potencial terapêutico por possuir propriedades anti-inflamatória, analgésica, anticonvulsivante, anticompulsiva, entre outras. No entanto, o CBD apresenta baixa biodisponibilidade, o que pode comprometer seu uso clínico. Além disso, os múltiplos efeitos farmacológicos do CBD ocorrem por diferentes mecanismos. Nesse sentido, o desenvolvimento de compostos com efeitos semelhantes ao CBD, porém mais potentes e/ou com melhor perfil farmacocinético, seria importante. Assim, no presente estudo, nós avaliamos os efeitos induzidos por um derivado fluorado do CBD, o HU-474, comparando-os com aqueles induzidos pelo CBD. Para isso, camundongos suíços machos foram submetidos a modelos animais sensíveis a drogas anticompulsivas (teste de enterrar esferas) e antinociceptivas (teste da placa quente, contorção abdominal e hiperalgesia inflamatória). Para o estudo dos mecanismos envolvidos nos efeitos destes compostos, foram utilizados os antagonistas dos receptores canabinóides CB1, AM251, e CB2, AM630. Adicionalmente, nós avaliamos se o HU-474 induziria os efeitos clássicos (tétrade canabinóide) observados após a administração de agonistas dos receptores CB1 como hipolocomoção, hipotermia, catalepsia e antinocicepção. Os possíveis efeitos antinociceptivos e da tétrade canabinóide induzidos pelo CBD e HU-474 foram comparados com os efeitos induzidos pelo WIN55,212-2, uma agonista dos receptores CB1/2. Foi observado que o CBD (30 e 60mg/kg) e o HU-474 (10mg/kg) induziram uma diminuição no número de esferas enterradas, efeito comparado ao da fluoxetina e atenuado pelos antagonistas AM251 e AM630. Como esperado, o WIN55,212-2 induziu a tétrade canabinóide, um efeito não observado com o CBD e HU-474. No teste da placa quente o HU-474 (30 mg/kg) e WIN55,212-2 (5mg/kg) induziram efeito antinociceptivo. O pré- tratamento com AM251 e AM630 atenuaram os efeitos do HU-474 e WIN55,212-2. No teste de contorção abdominal induzida pelo ácido acético, o CBD (30 e 90 mg/kg), HU-474 (30mg/kg) e WIN55,212-2 (3 e 5mg/kg) induziram efeito antinociceptivo caracterizado pela redução no número de contorções abdominais. O pré-tratamento com AM251 atenuou o efeito apenas do WIN55,212-2, mas não dos outros compostos. Já o antagonista AM630 não foi capaz de atenuar o efeito de nenhum dos compostos testados. No modelo de hiperalgesia inflamatória induzida por carragenina, o CBD (30 e 90mg/kg), HU-474 (3, 10 e 30mg/kg) e WIN55,212-2 (1mg/kg) foram capazes de diminuir a intensidade de hiperalgesia mecânica, avaliada pelo método de von Frey. Sendo que os efeitos do WIN55,212-2, CBD e HU-474 foram atenuados pelo pré-tratamento com AM251 e AM630. Estes resultados indicam que o HU-474 induz efeitos anticompulsivos semelhantes ao CBD, mas em doses mais baixas, através de mecanismo dependente da ativação dos receptores CB1 e CB2. Além disso, o HU-474 apresentou propriedades antinociceptivas em todos os testes utilizados, em doses semelhantes ou menores que o CBD. Os efeitos antinociceptivos dos três compostos testados foram dependentes da ativação de receptores CB1 e CB2, com exceção do teste de contorção abdominal, onde os efeitos do CBD e HU-474 não foram bloqueados por nenhum dos dois antagonistas testados. Diferente do WIN55,212-2, o CBD e HU-474 não induziram tétrade canabinóide. Esses resultados evidenciaram efeitos mais significativos do HU-474, indicando que a adição de um átomo de flúor a molécula de CBD foi capaz de melhorar o seu perfil farmacológico. Além disso, os resultados com o pré-tratamento com os antagonistas AM251 e AM630 nos permitem sugerir um mecanismo misto, visto que há o envolvimento dos receptores CB1 e CB2. Desse modo, esse novo composto poderia ser uma alternativa terapêutica para o tratamento do transtorno obsessivo-compulsivo, bem como dores agudas em doses menores que o CBD / Cannabidiol (CBD) has several therapeutic properties such as antiinflammatory, analgesic, anticonvulsivant and anticompulsive. These multiple pharmacological effects occur by different mechanisms. However, CBD exhibits low bioavailability, which may compromise its clinical use. Thus, the development of CBD analogues, more powerful and/or better pharmacokinetic profile would be interest. Here, we evaluated the effects of a fluorinated derivative of CBD, HU-474, comparing its effects with those induced by CBD. Male Swiss mice were submitted to animal models predictive to anti-compulsive (marble burying test) and antinociceptive drugs (hot plate, abdominal writhing and inflammatory hyperalgesia test). To study the mechanisms involved in their effects were used antagonist of the cannabinoid receptor CB1(AM251) and CB2 (AM630). We also evaluated whether HU-474 would induce the classic effects (cannabinoid tetrad) observed after the administration of CB1 receptors agonists. The cannabinoid tetrad is characterized by hypolocomotion, hypothermia, catalepsy, and antinociception. The possible antinociceptive effects and cannabinoid tetrad induced by CBD and HU-474 were compared with those induced by WIN55,212-2, a CB1/2 receptor agonist. CBD (30 and 60mg/kg), and HU-474 (10mg/kg) decreased the number of buried marble, an effect compared with fluoxetine an attenuated by AM251 and AM630. As expected, WIN55,212-2 induced the cannabinoid tetrad, an effect that was not observed after CBD or HU-474 administration. In the hot plate test, HU-474 (30mg/kg) and WIN55,212-2 (5mg/kg) induced antinociceptive effect. Pretreatment with AM251 and AM640 attenuated the effects induced by HU-474 and WIN55,212-2. In the abdominal writhing test induced by acetic acid, CBD (30 and 90mg/kg), HU-474 (30mg/kg) and WIN55,212-2 (3 and 5mg/kg) induced antinociceptive effects characterized by a reduction in the number of writhing. Pretreatment with AM251 only attenuated the effect of WIN55,212-2, but not of the other compounds, while AM630 didn\"t attenuated the effect of any of the tested compounds. In an inflammatory hyperalgesia model induced by carrageenan, CBD (30 and 90mg/kg), HU-474 (3, 10 and 30mg/kg) and WIN55,212-2 (1mg/kg) decreased the intensity of mechanical hyperalgesia measured by electronic von Frey method. The effects of all compounds were attenuated by the pretreatment with AM251 and AM630. These results indicate that HU-474 exhibits anti-compulsive effects similar to CBD, but at lower doses, through a mechanism dependent of the activation of CB1 and CB2 receptors. Furthermore, HU-474 showed antinociceptive properties in all tests at similar or lower doses than CBD. The antinociceptive effects of the three compounds tested were dependent on the activation of CB1 and CB2 receptors, excepted to the writhing test, where the effects of CBD and HU-474 were not attenuated by any of the two antagonists tested. Moreover, unlike WIN55,212-2, CBD and HU- 474 didn\'t induce cannabinoid tetrad. These results showed more significant effects of HU-474, indicating that the addition of fluoride improved the pharmacological profile of CBD. Furthermore, the results with pretreatment with the antagonist AM251 and AM630 allow us to suggest that these effects involve the activation of CB1 and CB2 receptors. Thus, this new compound could be a therapeutical alternative for the treatment of obsessive-compulsive disorder and acute pain in lower doses than CBD

This research focuses on obsessive-compulsive disorder (OCD) and how games focused on making the player feel empathy (empathy games) can increase the public’s general knowledge of the disorder. The disorder is currently commonly misunderstood and is not always taken seriously, something that potentially could hurt those with OCD. The stigma surrounding OCD sometimes makes people avoid getting the help they need, making them suffer in silence. The objective of the research was to define several game design principles that suggests what a developer should focus on when making an empathy game about OCD with the purpose to inform the general public. This was done by analyzing several scientific articles discussing either OCD or empathy games, and concluding the most important parts from them into game design principles. Four game design principles were found; target audience, reality, clarity, and includation. These have not been tested in a practical setting, but can possibly serve as guidelines when making an empathy game focusing on OCD.

This diploma thesis deals with selected problems that result from a person's obsessive compulsive disorder and that can influence and impact their social functioning. It also looks at selected possibilities for social work that can help to address these problems and to restore social functioning. The first chapter of this diploma thesis is focused on obsessive compulsive disorder. This chapter contains basic information about this mental disorder and the problems caused by this disease. The second chapter deals with the treatment of this disease. The third chapter focuses on the social functioning of a person suffering from obsessive compulsive disorder. This chapter contains selected examples of problems caused by this disease and their impact on the social functioning of a person suffering from obsessive compulsive disorder. These are examples from the scientific literature supplemented with examples from the particular case of Peter N.. The fourth chapter deals with selected possibilities of social work that can help to solve these problems and to restore social functioning.

The overarching aim of this dissertation is to use health services research methods to address three problems in behavioral health services. This dissertation seeks to address the knowledge gaps in behavioral health services through the generation of evidence intended to support evidence-based practices (EBP). Previous work has examined epidemiology of behavioral health disorders in the ED, but they have not attempted to examine disorders by the cause of injury. Chapter 2 examines the epidemiology of psychiatric disorders among adults who seek care in the emergency department (ED) by cause of injury. Data from a national hospital discharge survey was analyzed using logistic and multinomial regression. Estimates are given as average marginal effects (AME) to simplify the interpretation and application. Intentionally-caused injury and undetermined cause of injury are significantly associated with psychiatric disorders. Patients with undetermined cause of injury were more likely to be diagnosed with anxiety disorders, depressed mood, and psychoses relative to patients with unintentional injuries Since there are several treatment options for obsessive-compulsive disorder (OCD), including cognitive behavioral therapy (CBT), serotonin reuptake inhibitors (SRIs), and combinations of these, a comparison of treatment effects denominated in dollars is helpful when comparing risks and benefits. Chapter 3 builds on previous randomized control trials of treatments for OCD in children and adolescents by ranks the cost-benefits of first-line treatments. The analysis aggregates treatment effects from published trials in meta-analytic framework and a Monte Carlo simulation of 100,000 hypothetic children and adolescents to derive ranked cost-benefit. Treatments strategies starting with CBT, but not CBT and SRIs concurrently, were the most cost-beneficial. The relationship between cost-sharing and utilization of behavioral health services has been studied in the aggregate, but there has been little work examining the relationship by disorder and treatment modality. The aim of Chapter 4 is to examine the association between cost-sharing and utilization of psychotherapy and adherence to pharmacotherapy among insured adults with OCD. This chapter utilizes the Truven MarketScan Commercial Claims and Encounters dataset to perform zero-inflated negative binomial regression and logistic regression analyses. Increased cost-sharing was significantly, negatively associated with psychotherapy intensity and dose, but not associated with SRI adherence. This dissertation examined three different research questions to address gaps in the behavioral health services research. The findings of these chapters have implications for patients, clinicians, insurers, and policymakers. The results can be used to improve aspects of cost, quality, access, and efficiency of behavioral health services.

Obsessive-compulsive disorder (OCD) is associated with diminished quality of life and cognitive control dysfunction. Conflict adaptation is a reflection of cognitive control, and consists of the ability to detect conflict in previous trials and adjust performance on current trials. Conflict adaptation is thought to rely on interplay between the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC) for detecting conflict and signaling for increases in control, respectively. We hypothesized that individuals with OCD would show reduced conflict adaptation effects in response times, error rates, ACC activation, and dlPFC activation when compared with healthy control subjects. We also expected diminished conflict adaptation to be associated with poorer quality of life in those with OCD. Nineteen individuals with OCD and twenty psychiatrically-healthy controls completed a Stroop task while response times, error rates, and fMRI data were recorded. 2-Group (OCD, control) x 2-Previous Trial Congruency (congruent, incongruent), x 2-Current Trial Congruency (congruent, incongruent) ANOVAs were conducted for both behavioral and fMRI data. Indices of conflict adaptation were correlated with quality of life scores. There was a significant response time conflict adaptation effect collapsed across groups; however, there were no between-groups interactions or main effects. No error rate conflict adaptation was observed at any level of the analysis. On fMRI analyses, the dlPFC showed increased activation on incongruent relative to congruent trials collapsed across groups; however, no ACC activation differences were observed between current incongruent and congruent trials. Conflict adaptation-related activation was noted in the ACC collapsed across groups. The between-groups ANOVA revealed a significant cluster in the ACC with control participants showing greater ACC, medial prefrontal cortex, and left orbitofrontal cortex conflict adaptation activation-related activation relative to individuals with OCD. No between-groups differences were seen in the dlPFC. Conflict adaptation was not significantly related to quality of life. Individuals with OCD may use different neural processes to achieve similar behavioral results to those of healthy controls. Alternative explanations of conflict adaptation effects such as temporal learning theory are also discussed. Our hypothesized model for the ACC and dlPFC functioning as the evaluative and regulative components of cognitive control was only partly supported. ACC and dlPFC activation appeared to highlight different roles, but these roles may be independent rather than existing in a feedback loop. Although quality of life is significantly diminished in individuals with OCD, this loss of quality of life does not appear to be mediated by conflict adaptation differences.

It is of crucial importance to identify and disseminate effective treatments for paediatric obsessive-compulsive disorder (OCD). OCD is time-consuming and distressing, and can substantially disable functioning at school, at home, and with peers (Piacentini, 2003). Children who do not receive treatment are at risk of psychological difficulties in adulthood, including continued OCD, clinical anxiety and depression, personality disorders, and social maladjustment (Wewetzer et al., 2001). Two-thirds of adult cases of OCD develop in childhood, and adults with OCD have lower employment, poorer academic achievement, and lower marital rates compared to non-OCD adults (Hollander et al., 1996; Koran, 2000; Lensi et al., 1996; Steketee, 1993). The distressing nature of OCD in childhood, accompanying psychosocial impairment and risk of future psychopathology, underscore the need to identify effective treatments. The primary aim of this thesis was to expand knowledge of evidence-based treatments for paediatric OCD. A mixed-methodology approach was employed to examine key issues in this area. The first study used meta-analytic methodology to determine the evidence supporting available treatments for paediatric OCD. An extensive literature search revealed over 100 published reports of treatments, encompassing a broad array of theoretical approaches and treatment strategies. Examples of treatments used for paediatric OCD included psychodynamic therapy, pharmacotherapy, cognitive-behavioural therapy (CBT), hypnosis, family therapy, immunotherapy, and homeopathy. / Study 1 comprised the first known meta-analysis of randomised, controlled treatment trials (RCTs) for paediatric OCD. Included studies were limited to RCTs as they are the most scientifically valid means for determining treatment efficacy and provide a more accurate estimate of treatment effect by removing error variance associated with confounding variables. The literature search identified 13 RCTs containing 10 pharmacotherapy to control comparisons (N = 1016) and 5 CBT to control comparisons (N = 161). Random effects modelling yielded statistically significant pooled effect size (ES) estimates for pharmacotherapy (ES = 0.48, 95% CI = 0.36 to 0.61, p < .00001) and CBT (ES = 1.45, 95% CI = 0.68 to 2.22, p =.002). The results support the efficacy of CBT and pharmacotherapy, and confirm these approaches as the only two evidence-based treatments for paediatric OCD. Implications and suggestions for future research are discussed. The effectiveness of CBT provided impetus to further examine this treatment. Group CBT is an understudied treatment modality among children with OCD. It was hypothesised that group CBT would possess efficacy because of the effectiveness of individual CBT for children with OCD, the demonstrated effectiveness of group CBT among adults with OCD, the practical and therapeutic advantages afforded by a group treatment approach, and the embeddedness of the approach in robust psychological theory. The aim of the second study was to evaluate the efficacy of group CBT. The study comprised the largest known conducted randomised, placebo-controlled trial of group CBT for paediatric OCD. / Twenty-two children and adolescents with a primary diagnosis of OCD were randomly assigned to a 12-week program of group CBT or a credible psychological placebo. Children were assessed at baseline, end of treatment, and at 1 month follow-up. Outcome measures included the Children’s Yale-Brown Obsessive-Compulsive Scale, global measures of OCD severity, Children’s Depression Inventory, and parent- and child-rated measures of psychosocial functioning. An intention-to-treat analysis revealed that children in the group CBT condition had statistically significantly lower levels of symptomatology at posttreatment and follow-up compared to children in the placebo condition. Analysis of clinical significance showed that 91% of children that received CBT were ‘recovered’ or ‘improved’ at follow-up, whereas 73% of children in the placebo condition were ‘unchanged’. Effect size analysis using Cohen’s d derived an effect of 1.14 and 1.20 at posttreatment and follow-up, respectively. These effects are comparable to results from studies of individual CBT. This study supported group CBT as an effective treatment modality for paediatric OCD and demonstrated that the effect extends beyond placebo and nonspecific treatment factors. In addition to treatment efficacy, the inherent worth of a treatment lies in its adoption by the relevant clinical population. Children with OCD are known to be secretive and embarrassed about symptoms, and there is often a long delay between onset of symptoms and treatment-seeking (Simonds & Elliot, 2001). An important observation during the course of conducting the RCT was that a high rate (39%) of eligible families declined participation. / This led to the question, "What barriers prevent participation in group CBT for paediatric OCD?" Qualitative methodology was employed to address this research question. Eligible families that had declined participation in the RCT were contacted and invited to participate in semi-structured interviews that explored reasons for non-participation and positive and negative perceptions of group CBT. The average time between non-participation and interview was 1.33 years (SD = 3 months). Data were collected from nine families and thematic analysis methodology was utilised to identify emergent themes. Failure to participate was predicted by practical and attitudinal barriers. Practical barriers included a lack of time, distance, severity of OCD symptoms, financial, and child physical health. Attitudinal barriers included child embarrassment about OCD symptoms, child belief that therapy would be ineffective, fear of the social aspect of the group, lack of previous success with psychology, lack of trust in strangers, parental concern about the structure of the group, denial of a problem, and ‘not being ready for it’. Attitudinal barriers more frequently predicted treatment non-participation. Positive and negative perceptions of this treatment modality were informative. Parents showed no differences in preference for individual or group CBT. An important finding was that 56% of the children had not received treatment since parental expression of interest in the group CBT program. Application of the findings to methods that promote service utilisation is discussed.