Thesis advisor: Elizabeth Kensinger / Individuals with social anxiety disorder (SAD) tend to have emotional memory biases in the encoding and retrieval of social memories. Research has shown reduced heart rate variability (HRV) in clinical populations suffering from anxiety, including social anxiety. Heightened sympathetic activation—as measured by the electrodermal activity (EDA)—has also been associated with anxiety disorders. The aim of the present study was to examine the relation between HRV, social anxiety, and re-experiencing of emotional autobiographical memories. 44 healthy young adults were recruited from the Boston College campus through SONA. Participants were given an online survey that instructed them to retrieve 40 specific events from the past in response to 40 socially relevant cues. For each event, participants were instructed to provide a brief narrative, make several ratings for the event (on a scale from 1-7), and indicate the specific emotions they experienced both at the time of retrieval and of the event. Approximately one month after the completion of the memory survey, participants engaged in a 2-hour memory retrieval session while undergoing psychophysiological monitoring (heart rate, skin conductance, and respiration). Following the retrieval task, participants completed self-report questionnaires of social anxiety symptom severity and trait emotion regulation strategy (i.e., tendency to reappraise or suppress emotions). The present study found that positive memories had higher re-experiencing ratings as compared to negative memories. Contrary to the original study hypothesis, however, there was no significant interaction between average re-experiencing (or arousal) ratings of positive or negative social autobiographical memories and SAD likelihood. A nonlinear, cubic relationship was found between one of three metrics of HRV and social anxiety symptom severity. A significant effect was found between skin conductance and SAD likelihood, which was likely driven by an almost significance difference in skin conductance between the SAD unlikely and the SAD very probable groups; these findings provide further insight into the relationship between autonomic nervous system (ANS) functioning and social anxiety. Further, the present results suggest the intriguing possibility that there may be a nonlinear relationship between HRV and severity of social anxiety. Future research with a larger sample size is needed to corroborate these findings. / Thesis (BS) — Boston College, 2018. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Psychology.

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>

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.

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.