La presente investigación tiene como objetivo principal desarrollar un sistema experto que permita realizar el diagnóstico de trastorno de ansiedad, bajo la realización de los siguientes objetivos específicos: Definir las reglas que permitan perfilar mediante sus características claves el diagnóstico de trastorno de ansiedad, determinar la precisión del diagnóstico de trastorno de ansiedad y validar la funcionalidad del sistema experto con el especialista de la institución educativa. Con la aplicación de diversos recursos tecnológicos y la implementación de las reglas bajo la metodología Buchanan, se desarrolló un sistema experto con un motor de inferencia basado en reglas de conjunción hechas en el lenguaje Prolog, el cual brinda apoyo al momento de diagnosticar el trastorno de ansiedad. Con esto los estudiantes son diagnosticados o descartados en un menor tiempo. Logrando implementar un total de 236 reglas. Es así como, el sistema experto obtuvo una precisión del 94.7% en sus resultados, obteniendo solo tres falsos negativos de un total de 57 pruebas realizadas, bajo la supervisión de un psicólogo especialista y su experiencia, obteniendo así una correcta funcionalidad del software, diagnósticos confiables y sobre todo oportunos para que el psicólogo especialista brinde un tratamiento adecuado a los estudiantes de la institución educativa.

This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.

Social anxiety disorder (SAD) is a common psychiatric disorder associated with considerable suffering. Cognitive behaviour therapy (CBT) has been shown to be effective but a significant proportion does not respond or relapses, stressing the need of augmenting treatment. Using neuroimaging could elucidate the psychological and neurobiological interaction and may help to improve current therapeutics. To address this issue, functional and structural magnetic resonance imaging (MRI) were repeatedly conducted on individuals with SAD randomised to receive CBT or an active control condition. MRI was performed pre-, and post-treatment, as well as at one-year follow-up. Matched healthy controls were also scanned to be able to evaluate disorder-specific neural responsivity and structural morphology. This thesis aimed at answering three major questions. I) Does the brain’s fear circuitry (e.g., the amygdala) change, with regard to neural response and structural morphology, immediately after CBT? II) Are the immediate changes in the brain still present at long-term follow-up? III) Can neural responsivity in the fear circuitry predict long-term treatment outcome at the level of the individual? Thus, different analytic methods were performed. Firstly, multimodal neuroimaging addressed questions on concomitant changes in neural response and grey matter volume. Secondly, two different experimental functional MRI tasks captured both neural response to emotional faces and self-referential criticism. Thirdly, support vector machine learning (SVM) was used to evaluate neural predictors at the level of the individual. Amygdala responsivity to self-referential criticism was found to be elevated in individuals with SAD, as compared to matched healthy controls, and the neural response was attenuated after effective CBT. In individuals with SAD, amygdala grey matter volume was positively correlated with symptoms of anticipatory speech anxiety, and CBT-induced symptom reduction was associated with decreased grey matter volume of the amygdala. Also, CBT-induced reduction of amygdala grey matter volume was evident both at short- and long-term follow-up. In contrast, the amygdala neural response was weakened immediately after treatment, but not at one-year follow-up. In extension to treatment effects on the brain, pre-treatment connectivity between the amygdala and the dorsal anterior cingulate cortex (dACC) was stronger in long-term CBT non-responders, as compared to long-term CBT responders. Importantly, by use of an SVM algorithm, pre-treatment neural response to self-referential criticism in the dACC accurately predicted (&gt;90%) the clinical response to CBT. In conclusion, modifying the amygdala is a likely mechanism of action in CBT, underlying the anxiolytic effects of this treatment, and the brain’s neural activity during self-referential criticism may be an accurate and clinically relevant predictor of the long-term response to CBT. Along these lines, neuroimaging is a vital tool in clinical psychiatry that could potentially improve clinical decision-making based on an individual’s neural characteristics. / Social ångest är en av de vanligaste psykiska sjukdomarna. Mer än en miljon svenskar bedöms lida av detta. Social ångest leder ofta till svåra konsekvenser för den som drabbas, men även ökade kostnader för samhället har noterats, t ex i form av ökad sjukfrånvaro. Även om många som drabbas inte söker hjälp så finns effektiva behandlingar för social ångest, både farmakologiska och psykologiska behandlingar rekommenderas av Socialstyrelsen. Kognitiv beteendeterapi (KBT) är en evidensbaserad och rekommenderad psykologisk behandling för social ångest. Trots att nuvarande interventioner är effektiva så är det fortfarande en andel individer som inte blir förbättrade. Det finns en stor andel studier som visar att individer med social ångest, i jämförelse med friska individer, karakteriseras av överdriven aktivitet i ett nätverk som har till uppgift att tolka och reagera på hotfull information. Denna aktivitet är lokaliserad i rädslonätverket där området amygdala spelar en central roll. Det finns ett behov att utveckla nuvarande behandlingar och denna avhandling syftar till att öka vår förståelse för en neurobiologisk verkningsmekanism bakom KBT för social ångest. I detta forskningsprojekt har magnetresonanstomografi (MRT) använts för att undersöka personer som lider av social ångest. Upprepade mätningar har genomförts, innan, efter, och vid uppföljning ett år efter ångestlindrande behandling. Utöver detta har individer som inte lider av social ångest undersökts för att förstå hur patienter skiljer sig från friska personer, men också för att undersöka om behandlingen normaliserar patientens hjärna. Under tiden som deltagarna undersöktes med MRT genomfördes två experiment för att ta reda på hur hjärnan reagerar på affektiv information. Deltagarna tittade på bilder med ansikten som uttrycker emotioner, t ex arga och rädda ansiktsuttryck, samt information som innehöll kritiska kommentarer riktade till personen själv eller någon annan, t ex ”ingen tycker om dig” eller ”hon är inkompetent”. Strukturella bilder på deltagarnas hjärnor har också samlats in vid varje mättillfälle. Utöver detta fick alla deltagare instruktioner om att de efter MRT skulle hålla en muntlig presentation inför en publik. Denna uppgift är oftast den värsta tänkbara för individer med social ångest, och syftet med uppgiften var att relatera hjärnans struktur och aktivitet till hur mycket ångest som individerna upplevde inför denna situation. I arbetet med denna avhandling har tre frågor ställts. a) Uppstår strukturella och funktionella förändringar i rädslonätverket direkt efter avslutad KBT (Studie I och II)? b) Är de tidiga förändringarna efter behandlingen även kvarstående ett år senare (Studie III)? c) Kan hjärnans reaktioner i rädslonätverket förutspå vilka individer som kommer att bli förbättrade av en ångestlindrande psykologisk behandling på lång sikt? Resultat från studierna i denna avhandling sammanfattas nedan: Reaktioner till självriktad kritik i amygdala är överdrivna hos individer med social ångest, i jämförelse med friska individer Reaktioner i amygdala minskar efter att individerna blivit behandlade med KBT och minskningarna korrelerar till minskade symptom av social ångest Den strukturella volymen av amygdala korrelerar positivt med hur mycket ångest individerna upplever inför en muntlig presentation, och minskningen av dessa symptom korrelerar även med hur mycket volymen av amygdala minskar efter KBT Minskningen av amygdalavolym och den samtidigt minskade reaktiviteten i amygdala till självriktad kritik är korrelerade. Medieringsanalyser antyder att det är den minskade volymen som driver förhållandet mellan minskad reaktivitet och minskad ångest inför att hålla en muntlig presentation Den strukturella minskningen av amygdala ses både direkt efter behandlingens avslut, men även vid uppföljning ett år senare. Hjärnans reaktivitet till självriktad kritik i amygdala minskar direkt efter behandling, men är inte kvarstående vid uppföljning ett år senare Kopplingen mellan hjärnans reaktivitet till självriktad kritik i amygdala och dorsala främre cingulum var starkare hos de som inte blev förbättrade (jämfört med de som blev bättre) av en ångestlindrande behandling på lång sikt Med hjälp av en stödvektormaskin (en. support vector machine learning) och ett mönster av hjärnaktivitet i dorsala främre cingulum innan behandling påbörjades, predicerades (med 92% träffsäkerhet) vilka individer som ett år senare var fortsatt förbättrade av en effektiv psykologisk behandling Utifrån dessa observationer är slutsatserna att strukturell och funktionell påverkan på amygdala är en möjlig neurobiologisk mekanism för minskad social ångest efter KBT, samt att reaktivitet i främre cingulum kan ge kliniskt relevant data om vem som kommer att bli förbättrad av en psykologisk behandling. Denna information kan potentiellt vara viktig i framtidens psykiatri för att utveckla existerande behandlingar, men även för att stödja klinikers beslutsfattande huruvida en viss individ bör erbjudas en specifik behandling eller ej. / <p>Illustration on the cover by Jan Lööf. Cover image printed with permission from Jan Lööf and Bonnier Carlsen Förlag. The cover was art directed by Staffan Lager.</p><p>The thesis is reprinted and the previous ISBN was 9789176856888.</p>

L’objectif de la présente thèse était de caractériser le sommeil d’un groupe clinique d’enfants et d’adolescents ayant un trouble d’anxiété comme diagnostic primaire et le comparer à un groupe témoin. Dans un premier temps, nous avons vérifié si le profil de la fréquence cardiaque nocturne des enfants et des adolescents pouvait être regroupé selon le diagnostic. Pour ce faire, la fréquence cardiaque nocturne de 67 adolescents anxieux et 19 sujets non anxieux a été enregistrée à l’aide d’un équipement ambulatoire. Les résultats de cette étude montrent que le profil de la fréquence cardiaque nocturne chez les enfants anxieux varie selon le diagnostic. Alors que les adolescents non anxieux montrent un profil de la fréquence cardiaque nocturne plat, on retrouve les associations suivantes chez les adolescents ayant un trouble anxieux : a) un profil croissant de la fréquence cardiaque chez les adolescents ayant un trouble d’anxiété de séparation; b) un profil décroissant de la fréquence cardiaque chez les adolescents ayant un trouble d’anxiété généralisé; c) un profil en forme de U chez les adolescents ayant un trouble d’anxiété sociale. De plus, une association significative a été observée entre le diagnostic et la présence de fatigue matinale. L’association d’un profil de la fréquence cardiaque nocturne avec un diagnostic d’anxiété suggère la présence d’une dysrégulation de la modulation chronobiologique du système nerveux autonome. Étant donné que le profil de la fréquence cardiaque nocturne s’exprime différemment selon le diagnostic, qu’en est-il de l’architecture du sommeil? Dans un deuxième temps, nous avons enregistré le sommeil en laboratoire d’un groupe clinique de 19 jeunes ayant un trouble d’anxiété comme diagnostic primaire, avec comorbidités et médication et comparé à 19 jeunes non anxieux. Les résultats de cette étude ont montré que les participants du groupe anxieux ont une latence au sommeil plus longue, une latence au sommeil paradoxal plus longue et une durée d’éveil plus longue lorsque comparé au groupe témoin. L’évaluation subjective de la qualité du sommeil chez le groupe d’adolescents anxieux montre que leur auto-évaluation reflète les valeurs enregistrées en laboratoire. Nous avons également observé chez le groupe anxieux une fréquence cardiaque moyenne plus élevée et un index plus élevé d’apnée-hypopnée, bien que non pathologique. Nous avons également observé une association positive entre l’anxiété de trait et l’indice d’apnée-hypopnée et la latence au sommeil, ainsi qu’une association positive entre l’anxiété manifeste et la latence au sommeil paradoxal. Ces résultats suggèrent que le sommeil chez cette population est altéré, que des signes d’hypervigilance physiologique sont présents et qu'une association existe entre ces deux paramètres. Finalement, dans la troisième étude de cette thèse, nous avons analysé l’activité cardiaque pendant le sommeil en utilisant les paramètres temporels et fréquentiels de la variabilité cardiaque chez un groupe clinique de dix-sept enfants et adolescents ayant un trouble d’anxiété comme diagnostic primaire avec comorbidité et médication, et comparé à un groupe non anxieux. Les résultats ont montré que les participants du groupe anxieux, lorsque comparés au groupe non anxieux, présentent des intervalles interbattements plus courts, un indice temporel de la variabilité cardiaque représentant la branche parasympathique moindre, une activité des hautes fréquences normalisées moindre et un ratio basse fréquence sur haute fréquence augmenté. Plusieurs corrélations ont été observées entre les mesures cliniques de l’anxiété et les mesures de la variabilité cardiaque. Ces résultats viennent ajouter à la littérature actuelle un volet descriptif clinique à ce jour non documenté, soit l’impact de l’anxiété pathologique chez un groupe clinique d’enfants et d’adolescents sur le processus normal du sommeil et sur la régulation de la fréquence cardiaque. En résumé, les résultats de ces trois études ont permis de documenter chez un groupe clinique d’enfants et d’adolescents ayant de l’anxiété pathologique, la présence d’une altération circadienne du profil de la fréquence cardiaque, d’une architecture altérée du sommeil ainsi qu’une dysrégulation du système nerveux contrôlant l’activité cardiaque. / The aim of this thesis was to characterize, in a clinical group of children and adolescents with anxiety disorder as a primary diagnostic, the sleep period and to compare it to a control group. Firstly, we have verified if the nocturnal sleep pattern of children and adolescents could be grouped by psychiatric disorders. Sixty-seven children and adolescents with anxiety disorders and nineteen non anxious match controls were monitored using ambulatory recording equipment. Results showed that nocturnal heart rate pattern of anxious adolescents would vary accordingly with the diagnosis. While non anxious adolescents exhibit a flat nocturnal heart rate pattern through the night, anxious participants showed the following associations: a) increased nocturnal heart rate pattern associated with separation anxiety disorder; b) decreased nocturnal heart rate pattern associated with generalized anxiety disorder; and c) U shape nocturnal heart rate pattern associated with social phobia. Moreover, a significant association was found between anxiety diagnosis and presence of morning fatigue. The association between nocturnal heart rate patterns with anxiety suggests that the circadian modulation of heart rate is dysregulated, but what about the sleep macrostructure? Secondly, we have monitored in a sleep laboratory a clinical sample of nineteen adolescents with pathological anxiety, comorbidity and medication, and compared it to nineteen non anxious match controls. Results showed that anxious participants had longer sleep latency, longer REM sleep latency and longer awake period during sleep when compared to control participants. Compared to control participants, anxious patients subjectively reported sleep disturbances, manifested objective sleep disorders and presented no adaptation to the laboratory environment. Moreover, higher nocturnal heart rate and higher apnea-hypopnea index were observed in anxious group when compared to non anxious group. Significant positive associations were observed between Trait anxiety and apnea-hypopnea index as well as for sleep latency while manifest anxiety was associated to REM sleep latency. Results suggest that sleep of children and adolescents with pathological anxiety is altered, that signs of physiological hypervigilance are observed and that both are associated. Following previous results, we have analyzed in a third study heart rate variability during nocturnal sleep using both, times and frequency domains in a clinical sample group of seventeen children and adolescents with anxiety disorder as primary diagnostic with comorbidity and medication. Results showed that anxious when compared to non anxious, had a shorter interbeat interval, and had lower rMSSD values, less high frequency in normalized units and higher low frequency/high frequency ratio. Correlations were observed between clinical anxiety scores and time and frequency domains of heart rate variability. These results add to the growing body of literature that pathological anxiety in a clinical group of children and adolescents impact on sleep process and heart rate regulation during sleep. Overall findings add to the growing body of recent clinical literature, a sleep alteration description of a clinical sample of children and adolescents. From the three studies of this thesis, results showed that circadian heart rate pattern is altered, that sleep architecture is altered, and that the time and frequency domain of nocturnal heart rate variability is altered in a clinical group of children and adolescents with pathological anxiety.

DSM-IV-TR classifies hypochondriasis as a complex somatoform disorder, characterised by physical complaints for which no organic cause could be identified. DSM-5 replaced it with two new diagnostic terms: somatic symptoms disorder and illness anxiety disorder. The distinction was based on the presence or absence of somatic symptoms, and concerns have been raised with regards to the validity of these new diagnostic concepts. While there has recently been an increase in recognising the role of the underlying anxiety in this condition, the psychological needs of individuals with hypochondriasis remain unclear. It is conceivable that specific emotional and interpersonal dimensions play a mediating role in the onset of hypochondriacal presentations, and have explanatory power with regards to the improvement of tailored therapeutic interventions. The present study used a mixed methodology, with an emphasis on the qualitative component, to investigate emotions and the interpersonal aspects of hypochondriasis. Six young adult females meeting the diagnostic criteria for both DSM-IV-TR hypochondriasis and DSM-5 illness anxiety disorder formed a clinical group for the present study. Semi-structured interviews were administered and analysed in line with the Interpretative Phenomenological Analysis (IPA). Four major themes emerged from the qualitative data: 1) Early life experience; 2) Inward focus; 3) Learned helplessness; and 4) Experience of psychological therapy. Eight subordinate themes were identified: (i) Unmet emotional needs; (ii) Emotional isolation; (iii) There is something wrong with me; (iv) Emotional reasoning; (v) Self-fulfilling prophecy; (vi) External locus of control; (vii) Over-reliance on other people; and (viii) The experience of psychological therapy. Fifty-one female undergraduate psychology students formed a matched comparison group for the study and enabled a supplementary quantitative analysis to be conducted. The quantitative measures included measures of trait (TEIQue-SF) and ability emotional intelligence (MSCEIT) as well as a measure of sociotropy-autonomy (SAS). The quantitative data showed that the clinical group scored significantly lower than the comparison group on the measures of trait emotional intelligence, understanding emotions, and autonomy. Additionally, the clinical group scored significantly higher than the comparison group on the measure of sociotropy. The theoretical and therapeutic recommendations are discussed in light of the limitations of the present study. In conclusion, emotional and interpersonal aspects of DSM-IV-TR Hypochondriasis and DSM-5 illness anxiety disorder in young women provide a useful framework for the conceptualisation and therapeutic management of these conditions. It appears that with its scientific knowledge base, therapeutic flexibility, focus on reflective practice, and the emphasis on an effective working relationship, the discipline of counselling psychology is well-suited to address the needs of participants with hypochondriacal presentations.

[pt] Sensibilidade à Ansiedade (ex: medo dos sintomas relacionados à ansiedade assim como a crença de que esses sintomas possam ter conseqüências desastrosas) é um importante constructo psicológico envolvido na etiologia de diferentes Transtornos de Ansiedade. O presente estudo avaliou as propriedades psicométricas e a estrutura fatorial da Escala de Sensibilidade à Ansiedade Revisada (ESA-R) em 585 pacientes brasileiros com diagnóstico primário de Transtorno de Ansiedade. Os resultados indicaram que a presente versão da ESAR possui boa consistência interna e boa correlação de coeficiente item-total. A análise fatorial exploratória sugeriu uma estrutura hierárquica composta por um fator único de primeira ordem e quatro fatores de segunda ordem relacionados a: 1) medo dos sintomas respiratórios e cardiovasculares, 2) medo de descontrole cognitivo, 3) medo que as reações de ansiedade sejam observadas publicamente, e 4) medo dos sintomas gastrintestinais. Os fatores de primeira e segunda ordem da ESA-R comparados com os diferentes grupos de Transtorno de Ansiedade indicaram que pacientes com Transtorno do Pânico apresentaram um escore significativamente mais elevados nas dimensões da ESA - R, com exceção para o fator de segunda ordem medo do descontrole cognitivo. / [en] Anxiety sensitivity (i.e., fear of anxiety-related symptoms due to the belief that these symptoms will produce harmful consequences) is an important psychological construct involved in the etiology of different anxiety disorders. The present study evaluated the psychometric proprieties and the factor structure of the Anxiety Sensitivity Index-Revised (ASI-R) among 585 Brazilian patients with primary anxiety disorder diagnosis. Results indicated that the present version of the ASI-R had good internal consistency and item-total correlation coefficients. Exploratory factor analyses suggested a hierarchical structure composed by a single higher-order factor and four lower-order factors related to 1) fear of respiratory and cardiovascular symptoms, 2) fear of cognitive dyscontrol, 3) fear of publicly observable anxiety reactions, and 4) fear of gastrointestinal symptoms. ASI-R higher- and lower-order factor scores comparisons across the different anxiety disorder groups indicated that panic disorder patients scored significantly higher in the ASI-R dimensions, except for the fear of cognitive dyscontrol lowerorder factor.

Diferentes ensaios clínicos randomizados demonstram que a Terapia Cognitivo-Comportamental (TCC) é muito efetiva no tratamento do Transtorno de Ansiedade Social (TAS). Entretanto, uma quantidade significativa de pacientes não apresentam melhora após a finalização da intervenção com TCC. Tal dado indica a necessidade de desenvolver novas estratégias de tratamento para o TAS. A Terapia Cognitiva Processual (TCP) é uma nova abordagem dentro do campo da TCC que tem como principal objetivo auxiliar os pacientes a identificar e modificar suas crenças centrais disfuncionais, sendo o Processo uma das principais técnicas utilizadas. Algumas pesquisas têm demonstrado a efetividade do Processo no tratamento do TAS e de outros transtornos psiquiátricos. Entretanto, novas pesquisas são necessárias para avaliação não somente de tal técnica, mas de todo o protocolo de intervenção da TCP. Esta pesquisa objetivou avaliar se participantes que receberam uma intervenção individual em TCP apresentam diferenças em relação a sintomas de ansiedade social, medo da avaliação negativa, esquiva e desconforto social, ansiedade, depressão, sofrimento psíquico, distorções cognitivas e viés atencional. Este é um ensaio clínico randomizado que comparou um grupo que recebeu intervenção em TCP e um grupo lista de espera no tratamento do TAS. O estudo apresenta três grupos de pesquisa: o TCP (n =18), o lista de espera (n =21) e o saudável (n =19). Um pesquisador independente ao estudo realizou a distribuição aleatória dos participantes com TAS entre os grupos TCP e lista de espera. Foram realizadas avaliações no pré e pós-teste através de diferentes escalas de auto-relato e do teste de Stroop emocional. Adicionalmente, o grupo TCP respondeu tais escalas a cada quatro sessões. O tratamento foi realizado em 16 sessões com duração de 1h30min cada utilizando a TCP no formato individual. Houve uma redução significativa nos sintomas de ansiedade social, ansiedade, depressão, esquiva e desconforto social, e sofrimento psíquico no grupo TCP ao longo do tratamento (p < 0,05). Tais reduções foram associadas a tamanhos de efeito grandes. Não foram observadas mudanças em nenhum dos instrumentos utilizados no grupo lista de espera (p > 0,05). Houve ainda uma significativa redução no medo da avaliação negativa após a utilização do Processo no grupo tratado, além de uma redução em distorções cognitivas (p < 0,05). Não foram observadas diferenças no pré e pós-teste em relação ao viés atencional nos três grupos da pesquisa (p > 0,05). Este estudo sugere que a TCP pode ser uma nova abordagem clínica efetiva no tratamento do TAS associado à diferentes comorbidades, haja vista que houve uma redução em sintomas de ansiedade social e sintomas comórbidos / Different randomized clinical trials show that Cognitive Behavioral Therapy (CBT) is highly effective in the treatment of Social Anxiety Disorder (SAD). However, a large number of patients do not show improvement after receiving CBT. This indicates that it is important to develop new treatments for SAD. Trial-Based Cognitive Therapy (TBCT) is a new approach within the field of CBT area. It aims to help patients to identify and to modify their dysfunctional core beliefs. One of the main TBCT techniques proposed by TBCT is the Trial. Some research studies have demonstrated the effectiveness of Trial in the treatment of SAD, and other disorders. However, further investigation is needed to firmly establish the efficacy not just for the Trial technique, but also the TBCT approach as a treatment for SAD and other disorders. This research aims to evaluate wheter SAD participants receiving TBCT individual-sessions differ from a SAD waiting list group condition regarding symptoms of social anxiety, fear of negative evaluation, social avoidance and distress, anxiety, depression, mental suffering, and attentional bias. This is a randomized clinical trial comparing TBCT and a Waitlist control condition for the treatment of SAD. The study has three groups: TBCT (n =18), Wailist (n =21), and healthy group (n =19). An independent researcher to study distributed randomly the participants with SAD between TBCT or Waitlist condition. Assessments were made at pre and post-test using several self-report scales, and the emotional Stroop test in the three groups. Additionaly, the TBCT group answered these scales each four sessions. The treatment was delivered in sixteen 1.5 hour sessions using the individual TBCT format. There were reductions in social anxiety, anxiety, depression, social avoidance and distress, and mental suffering symptoms at TBCT group (p < 0.05), but not in the Waitlist group (p > 0.05). Those reductions were associated with a large effect size. There was a significant reduction at fear of negative evaluation after Trial use, and reductions at cognitive distortions throughout the treatment as well (p < 0.05). There were no differences among the three groups regarding attentional bias at pre-test nor at post-test (p > 0.05). This study suggests that TBCT may be a new effective clinical approach to treat SAD associated with high rates of comorbidity, as there were significant reductions in the comorbid symptoms

O Transtorno de Ansiedade Social (TAS) consiste em um medo acentuado e persistente de situações sociais ou de desempenho nas quais o indivíduo poderia sentir vergonha. Dentre os transtornos de ansiedade, o TAS é um dos mais prevalecentes, sendo considerado o quinto transtorno mais incapacitante, contudo, a busca por tratamento é muito baixa. Diferentes estudos clínicos randomizados evidenciam que a TCCG apresenta resultados satisfatórios e duradouros, sendo considerada padrão ouro de intervenção para TAS, porém, ainda assim, uma parcela de pacientes com TAS não respondem ao tratamento. Assim sendo, o objetivo deste trabalho foi investigar o efeito de uma intervenção em grupo de exposição com alto custo social em pacientes com TAS sobre variáveis psicológicas e também sobre a qualidade de memória. A intervenção utilizada nesse estudo foi a proposta por Hofmann e Otto (2008). Dentre as variáveis psicológicas estudadas foram avaliadas mudanças em sintomas de ansiedade social, ansiedade, medo da avaliação negativa, esquiva e desconforto social, depressão e sintomas de transtornos psiquiátricos comuns. Participaram desse estudo 58 adultos, compondo três grupos experimentais diferentes: o grupo de comparação sem TAS, que consiste em participantes sem sintomas clínicos, o grupo de comparação com TAS, que são participantes portadores de TAS os quais não realizaram a intervenção durante a pesquisa (grupo lista de espera) e o grupo de portadores de TAS participaram da intervenção (grupo TCCG). Um pesquisador independente ao estudo realizou a distribuição aleatória dos participantes com TAS entre os grupos TCCG e lista de espera. Foram realizadas avaliações no pré e pós-teste através do Inventário de Fobia Social (SPIN), Inventários de Ansiedade e Depressão de Beck (BAI e BDI-II), Escala de Medo da Avaliação Negativa (FNE), Escala de Esquiva e Desconforto Social (SADS), Questionário sobre a saúde do paciente (PHQ-9), Questionário de Autorrelato (SRQ) e teste de falsas memórias. Assim, os resultados encontrados evidenciam que a intervenção alcançou redução significativa nos sintomas de ansiedade social, ansiedade geral, depressão e sintomas de transtornos mentais comuns, mostrando que foi uma intervenção efetiva. Além disso, os escores relacionados à ansiedade geral, depressão e sintomas de transtornos mentais comuns, após a intervenção foram equiparados com o escore obtidos pelo grupo de participantes saudáveis, evidenciando a excelente eficácia do processo de intervenção. A eficácia também pode ser constatada a partir da mensuração do tamanho de efeito grande encontrado no estudo relacionado ao principal instrumento de avaliação de TAS utilizado (SPIN), ou seja, esse estudo evidenciou que a forma psicoterápica utilizada atingiu o objetivo esperado da intervenção considerada padrão ouro. No que concerne às medidas relacionadas à qualidade de memória, a hipótese inicial relacionava-se à teoria de que os indivíduos ansiosos sociais apresentariam um número maior de falsas memórias e/ou uma redução de memórias verdadeiras, porém essa hipótese não foi confirmada. / Social Anxiety Disorder (SAD) consists of a marked and persistent fear of social or performance situations in which the individual could feel shame. Among the anxiety disorders, SAD is one of the most prevalent, considered the fifth most disabling disorder, however, the search for treatment is very low. Different randomized clinical trials show that Cognitive-Behavioral Group Therapy (CBGT) presents satisfactory and long-lasting results, which is considered the gold standard of intervention for SAD, however, a portion of patients with SAD do not respond to treatment. Thus, the objective of this study was to investigate the effect of a group intervention related to high social cost exposure in patients with SAD about psychological variables and memory quality. The intervention used in this study was proposed by Hofmann and Otto (2008). Among the psychological variables studied changes in symptoms of social anxiety, anxiety, fear of negative evaluation, avoidance and social discomfort, depression and symptoms of common psychiatric disorders were evaluated. Fifty-five adults participated in this study, composing three different experimental groups: the comparison group without SAD, which consists of participants without clinical symptoms, the comparison group with SAD, participants with SAD who did not receive intervention during the research (Waitlist control condition), and the group of SAD patients who participated in the intervention. An independent researcher to study distributed randomly the participants with SAD between CBGT or Waitlist condition. Assessments were made at pre and post-test using Social Phobia Inventory (SPIN), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Fear of Negative Evaluation (FNE), Social Avoidance and Distress Scale (SADS), Patient Health-Questionnaire (PHQ-9), Self-Report Questionnaire (SRQ), and false memories test in the three groups. The results showed that the intervention achieved a significant reduction in the symptoms of social anxiety, general anxiety, depression and symptoms of common mental disorders, showing that it was an effective intervention. In addition, the scores related to general anxiety, depression and common mental disorder symptoms after the intervention were similar to the scores obtained by the group of healthy participants, evidencing the excellent efficacy of the intervention process. Efficacy can also be seen from the measurement of the large effect size found in the study evaluated by the main evaluation instrument of SAD used (SPIN), this study achieved the expected goal of the gold standard considered intervention. Concerning measures related to memory quality, the initial hypothesis was that social anxious individuals would present a greater number of false memories and / or a reduction of true memories, but this hypothesis was not confirmed.

Objetivos: Estudar a confiabilidade e validade de uma versão brasileira dos módulos Episódio Depressivo Maior (EDM) e Transtorno de Ansiedade Generalizado (TAG) do Mini International Neuropsychiatric Interview TRACKING (MINI-TRACKING); comparar a evolução de pacientes com diagnóstico de EDM e TAG seguidos por equipes de Estratégia de Saúde da Família (ESF) com acesso ao modelo de Cuidado Colaborativo (CC) em Saúde Mental versus um grupo de pacientes seguidos por equipes sem acesso ao CC. Metodologia: O estudo envolveu quatro equipes de ESF vinculadas à Faculdade de Medicina de Ribeirão Preto (FMRP), sendo duas com acesso ao CC e duas sem CC. Um total de 147 pacientes foram entrevistados com o objetivo de rastrear transtornos mentais com a aplicação do WHO-5 e do COOP-WONCA Quadro Sentimentos. Após a confirmação diagnóstica de EDM e/ou TAG, com a entrevista MINI, 42 pacientes foram selecionados e concordaram em participar da pesquisa. Estes pacientes foram acompanhados por doze meses por um médico de família (MF), que aplicou periodicamente a cada oito a doze semanas os módulos EDM e/ou TAG do MINI-TRACKING. Para avaliação da fidedignidade e da validade concorrente, um psiquiatra (cego quanto ao diagnóstico do MF e quanto a qual equipe seguia o paciente) aplicou, com intervalo máximo de 72h do MF, os mesmos módulos do MINI-TRACKING, o PHQ-9 e/ou o GAD-7. Resultados: Não foi encontrada diferença estatisticamente significativa entre os pacientes das equipes com e sem CC no que se refere as características clínicodemográficas. Os itens individuais dos dois módulos do MINI-TRACKING mostraram boa fidedignidade inter-avaliadores (Kappa entre 0,78 e 0,98), bem como seus escores totais (Coeficiente Intra-classe de 0,996 e 0,993 para EDM e TAG, respectivamente). Os módulos EDM e TAG mostraram também boa validade concorrente com as escalas PHQ-9 e GAD-7 (coeficiente de Pearson 0,994 e 0,976, respectivamente). Trinta pacientes (quinze de equipes com CC e 15 de equipes sem CC) completaram as cinco avaliações no decorrer de um ano de seguimento. A ANOVAmr destes pacientes mostrou diferenças significativas no fator tempo e na interação tempo x intervenção, com diminuição significativamente maior dos escores do MINI-TRACKING nos pacientes seguidos pelas equipes com CC. Conclusão: Os módulos EDM e TAG do MINI-TRACKING são uma opção confiável para o seguimento de pacientes com estes diagnósticos. Este estudo também mostrou, de forma preliminar, que o CC em saúde mental é uma estratégia eficaz na redução de sintomas dos pacientes com EDM e TAG na Atenção Primária. / Objectives: To study the reliability and validity of a Brazilian version of the Mini International Neuropsychiatric Interview - TRACKING (MINI-TRACKING) modules for Major Depressive Episode (MDE) and Generalized Anxiety Disorder (GAD); To compare the outcomes of patients diagnosed with MDE and GAD followed by teams of the Family Health Strategy (FHS) with access to the Mental Health Collaborative Care model (CC) versus a group of patients followed by teams without access to CC. Methodology: The study involved four FHS teams of the Faculty of Medicine of Ribeirão Preto (FMRP), two of them with access to CC and two without it. A total of 147 patients were tracked for mental disorders with the application of the WHO-5 and the COOP-WONCA Chart Feelings. After confirming the diagnosis of MDE and/or GAD using the MINI interview, 42 patients were selected and agreed to participate. These patients were followed for twelve months by a family physician (FP), who applied regularly every eight to twelve weeks the MDE and/or the GAD MINI-TRACKING modules. To assess the reliability and concurrent validity, a psychiatrist (blind to the diagnosis and to which team the patient was followed) also applied the same modules of the MINI-TRACKING, the PHQ-9 and/or the GAD-7, with a maximum interval of 72 hours of the FP. Results: There was no statistically significant difference between the patients with and without CC teams regarding demographic and clinical characteristics. The individual items of the two MINI-TRACKING modules showed good inter-rater reliability (kappa between 0.78 and 0.98), as well as their total scores (Intra-class coefficient of 0.996 and 0.993 for MDE and GAD, respectively). The MDE and GAD modules also showed good concurrent validity with PHQ-9 and GAD-7 scales (Pearson coefficient 0.994 and 0.976, respectively). Thirty patients (fifteen with CC and 15 without CC) completed the five assessments during one year of follow up. The repeated-measures analysis of variance (rmANOVA) showed significant differences in the time factor and the interaction time x intervention, decrease significantly higher of the MINI-TRACKING scores in the patients followed by teams with CC. Conclusion: MINI-TRACKING MDE and GAD modules are a reliable option for following patients with these diagnoses. This study also showed, preliminarily, that CC in Mental Health is an effective strategy in reducing symptoms in Primary Care patients with MDE and GAD.

This dissertation is divided into three parts. The first part aimed to investigate the cannabidiol anxiolytic effect in treatment-naïve individuals with social anxiety disorder through simulation of public speaking. Twenty-four never-treated social anxiety disorder subjects were allocated to receive 0 or 600 mg cannabidiol (CBD; n=12) in a double-blind randomized design. The same number of controls performed the simulation of a public speaking test without receiving any medication. Pretreatment with CBD significantly reduced anxiety, cognitive impairment, and discomfort in speech performance and significantly decreased alertness in their anticipatory speech. The placebo group displayed higher anxiety, cognitive impairment, discomfort, and alertness when compared with controls as assessed with the Visual Analogue Mood Scale (VAMS). The SSPS-N scores showed significant increases during testing of the placebo group that was almost abolished in the cannabidiol group. No significant differences were observed between the cannabidiol and control groups in SSPS-N scores or in cognitive impairment, discomfort, and alertness factors of the VAMS. The second part evaluated healthy subjects\' x y during a public speaking test following a high rimonabant oral dose, to understand better the possible pharmacological approaches for anxiety disorder treatment. Twenty four participants were randomly allocated to receive 0 or 90 mg rimonabant (n=12) in a double-blind design. No significant adverse effects were reported in either group. Participants who received rimonabant showed increased anxiety levels compared to placebo during anticipatory speech and performance measurements. Rimonabant treatment did not affect sedation, cognitive impairment, discomfort, blood pressure, heart rate, self-statements during public speaking, or bodily symptoms scales. Increased anxiety may reflect lower endocannabinoid activity in CB1 receptors and CB1 p \' possible role in modulation of anxiety and anxiety disorders. The third part aimed to monitor cannabinoid blood concentrations during sustained abstinence from chronic daily cannabis smoking. Thirty male chronic daily cannabis smokers resided on a secure clinical research unit for up to 33 days, with blood collected once daily. ?9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) whole blood concentrations were quantified by two-dimensional gas chromatography-mass spectrometry. Twenty-seven of 30 participants were THC-positive on admission, with a median (range) concentration 1.4 ng/mL (0.3-6.3). THC decreased gradually with only 1 of 11 participants negative at 26 days; 2 of 5 participants remained THC-positive (0.3 ng/mL) for 30 days. 5.0% f p p h TH >=1 0 g/ L f 12 y M 11-OH-THC w 1 1 g/ L w h >=1 0 g/ L 24h THCCOOH detection rates were 96.7 on admission, decreasing slowly to 95.7 and 85.7% on days 8 and 22, respectively; four of 5 participants remained THCCOOH positive (0.6-2.7 ng/mL) after 30 days and one remained positive on discharge at 33 days. THC was quantified in some participants for 30 days, albeit in low concentrations, due to the large cannabinoid body burden from extended exposure / Esta tese é dividida em três partes. A primeira parte consiste em investigar o efeito ansiolítico do canabidiol na ansiedade social através do teste de simulação de falar em público. Vinte e quatro sujeitos com ansiedade social, nunca tratados, receberam placebo ou canabidiol (CBD) 600 mg (n=12) em um estudo randomizado e duplo-cego. O mesmo número de indivíduos saudáveis realizaram o teste de simulação de falar em público sem receber medicação. A administração do CBD reduziu significativamente a ansiedade, sedação física e outros sentimentos e atitudes durante a fase de estresse, e diminui o nível de alerta na fase pré-estresse. O grupo placebo apresentou níveis elevado de ansiedade, sedação física, outros sentimentos e atitudes, e alerta comparado com o grupo controle. A pontuação do SSPS-N evidenciou aumento significativo durante o teste no grupo placebo, enquanto que o CBD reduziu estes níveis. Não houve diferenças significativas entre os grupos CBD e controle na SSPS-N e nos fatores sedação física, outros sentimentos e atitudes e alerta, da Visual Analogue Mood Scale (VAMS). A segunda parte do estudo avaliou a ansiedade em indivíduos saudáveis que receberam alta dose oral de rimonabanto e submetidos ao teste de simulação de falar em público, para melhor entendimento do possível mecanismo farmacológico para tratamento de transtornos de ansiedade. Vinte e quatro sujeitos saudáveis receberam placebo ou rimonabanto 90 mg (n=12) em um randomizado e duplo-cego. Não foi observado efeitos adversos significativo em ambos grupos. O grupo rimonabanto apresentou maiores níveis de ansiedade na fase pré-estresse e durante o estresse. Não houve diferença significativa quanto aos demais fatores avaliados entre os grupos. O aumento na ansiedade após administração do rimonabanto pode-se ao fato de haver diminuição no sistema endocanabinóide nos receptores CB1 e a possível modulação na ansiedade clínica e patológica. A terceira parte objetivou quantificar canabinóides no sangue total em usuários crônicos de cannabis durante abstinência supervisionada. Trinta usuários crônicos de cannabis, do sexo masculino, permaneceram no centro de pesquisa por até 33 dias, com coleta de sangue uma vez ao dia. ?9-tetrahidrocanabinol (THC), 11-hidróxi-THC (11-OH-THC) e 11-nor-9-carbóxi-THC (THCCOOH) foram quantificados no sangue por meio da cromatografia gasosa-espectrometria de massa bidimensional. Vinte e sete de 30 usuários foram positivos para THC no ingresso do estudo, com concentração mediana (variação) de 1.4 ng/mL (0.3-6.3). Níveis de THC diminuíram gradativamente com somente 1 de 11 participantes negativo no dia 26; 2 de 5 indivíduos permaneceram positivos para THC (0.3 g/ L p 30 5 0% j TH >=1 0 g/ L p 12 ç mediana de 11-OH-TH f 1 1 g/ L g >=1 0 g/ L pó 24h. A taxa de detecção de THCCOOH foi 96.7% no ingresso, diminuindo gradativamente para 95.7 e 85.7% nos dias 8 e 22, respectivamente; 4 de 5 sujeitos permaneceram positivo para THCCOOH (0.6-2.7 ng/mL) após 30 dias e um permaneceu positivo no 33º dia. Foi detectado THC em alguns indivíduos por 30 dias, porém em baixas concentrações, devido a extensa eliminação do canabinóide em decorrência da exposição crônica