Treatment dropout is a pervasive phenomenon that can preclude clients from benefiting fully from psychotherapy. Research efforts to understand the phenomenon in the preceding decades yielded few consistent results. The investigation of intrinsic client and therapist factors gave way to the more recent exploration of dynamic therapeutic process factors potentially influencing the dropout process. The availability of periodic treatment outcome measurement instruments has helped client-focused research explore the effects of treatment response as a process factor on aspects of psychotherapy. As an added benefit, real-time treatment response measures, such as the Outcome Questionnaire, offer the possibility of timely adjustment in clinical intervention to meet evolving client needs and enhance therapeutic treatment. This present study primarily sought to explore the relationship between psychotherapy dropout and treatment response patterns in terms of clients' psychosocial well-being as measured by the Outcome Questionnaire. The results suggest that treatment response patterns alone may not effectively predict dropout probabilities. Even so, the measure's sub-component assessing the client's subjective experience of symptom distress is shown to be more accurate in predicting dropout than the composite Outcome Questionnaire measure or any other component scale. This finding conceivably highlights the relative importance of symptom distress in the dropout process for the sampled clients. Those clients reporting higher levels of symptom distress appeared to be associated with greater probabilities of dropout termination. Additionally, prior research has recognized a likely mediated relationship between higher client educational attainment and lower dropout probabilities - a trend also observed in this study's sampled population. As one of its expressed intents, this study examined educational attainment's moderating effect on the relationship between aspects of client treatment response and dropout probabilities. While showing educational attainment to be a relevant factor in assessing dropout risks, the analysis results indicate that this client characteristic variable's interactional effect on the evaluated treatment response pattern feature is weak and statistically nonsignificant. The present study contributes to the research literature through providing some clarification to the importance of treatment response in the prediction of psychotherapy client dropout.

Adolescence is a developmental period characterized by profound social and emotional changes. Counseling can serve as a protective factor for decreasing the long-term negative emotional effects. Despite this fact, counselors continue to struggle with high rates of attrition among adolescent clients. When examining trends of client persistence in counseling across the lifespan, researchers found a relationship between the presence of internalizing and externalizing behaviors. Additionally, they found that high levels of familial stress predicted premature termination from counseling. The purpose of the current study was to create a predictive model of adolescent persistence in counseling. I examined both personal and environmental characteristics of adolescents who sought counseling services (N = 72) from an on-campus university counseling clinic that serves as a training facility for master’s and doctoral students at an accredited counselor education program in the southwestern United States. Participants were predominantly White (67.6%, n = 50), with a mean age of 14.23 (SD = 1.65). Nearly 60% (n = 44) of the clients were female, and 37.8% were male (n = 28). Beyond descriptive variables, eight predictor variables were examined: adolescent involvement in their intake, time spent on the wait list, four domains of parental stress, and parent perceptions of adolescent internalizing and externalizing behaviors. A multiple linear regression was conducted to understand how much of the variance in the number of counseling sessions attended by adolescent clients was explained by the predictor variables. The regression analysis was statistically significant (p = .008) and accounted for 29.1% (R2adj = .192) of the variance in sessions attended. Of the variables examined, externalizing behaviors (42.82%) accounted for the most variance in sessions attended, followed by whether the adolescent was involved in the intake (29.16%), internalizing behaviors (12.96%), and parent-focused stress (10.30%). An examination of the two strongest predictors in correlation to the number of sessions attended revealed a negative relationship with externalizing behaviors and a positive relationship with involvement in the intake, suggesting that adolescents who present with externalizing behaviors and who are not involved in their intake are likely to attend fewer counseling sessions. To understand the differences among adolescents who prematurely terminate from counseling and those who persist in counseling, I conducted a series of univariate and multivariate analyses. Comparing the means of the predictor variables revealed no significant differences between any of the predictor variables examined, although internalizing and externalizing behavior scores fell within the borderline clinical range for adolescents who persisted in counseling. Finally, a predictive discriminant analysis to assess to what degree identified variables predicted premature termination from or persistence in counseling yielded a 75% hit rate. Given this knowledge, counselors may be able to pro-actively identify adolescents who are at risk of prematurely terminating from counseling and implement retention strategies.

Les mutations non sens introduisent un codon stop prématuré dans une phase ouverte de lecture. Ce type de mutation est retrouvé chez environ 11% des patients atteints de maladies génétiques et dans de nombreux cancers. En effet, entre 5 et 40% des mutations affectant des gènes suppresseurs de tumeurs sont des mutations non sens. La conséquence de la présence d’une mutation non sens dans un gène est la dégradation rapide de l’ARN messager correspondant, par l’activation d’un mécanisme de surveillance des ARN appelé NMD (pour nonsense-mediated mRNA decay) conduisant à une absence d’expression du gène mutant. Dans le cas des cancers, l’absence d’expression d’un gène suppresseur de tumeurs tel que TP53, perturbe un ensemble de processus biologiques dont l’apoptose, facilitant ainsi la progression tumorale.En utilisant un système de criblage moyen débit permettant d’identifier des molécules capables de ré-exprimer des gènes porteurs d’une mutation non sens en inhibant le NMD et/ou en activant la translecture, plusieurs molécules ont été identifiées. La translecture est un mécanisme naturel conduisant à l’incorporation d’un acide aminé à la position du codon stop prématuré au cours de la traduction. Parmi les molécules identifiées, je me suis intéressée à un extrait végétal nommé H7 et au composé CNSM1 (pour corrector of nonsense mutation 1) qui permettent une ré-expression très efficace du gène TP53 lorsqu’il est porteur d’une mutation non sens. J’ai caractérisé ces composés en montrant notamment la ré-expression du gène TP53 porteur d’une mutation non sens dans différentes lignées cellulaires issues de différents cancers. J’ai montré également la très faible toxicité de ces molécules, validant leur potentielle utilisation en clinique. Mon étude a aussi permis de montrer que la protéine p53 synthétisée est fonctionnelle puisqu'elle est capable d’induire l’activation transcriptionnelle d’un de ses gènes cibles, le gène TP21.En permettant la ré-expression du gène suppresseur de tumeur mutant, des molécules comme CNSM1 ou H7 restaurent la capacité des cellules à entrer en apoptose et pourraient aussi réduire certaines résistances à la chimiothérapie.De plus, par une approche d’édition du génome, j’ai confirmé le lien existant entre le blocage du cytosquelette et l’inhibition du NMD. J’ai aussi identifié deux protéines impliquées dans le réarrangement du cytosquelette qui pourraient être ciblées pour inhiber le NMD en thérapie et ré-exprimer une protéine tronquée fonctionnelle. L’utilisation de H7 ou de CNMS1 pourrait ainsi être couplée à une inhibition du NMD pour optimiser la correction des mutations non sens. Ces molécules correctrices de mutations non sens représentent de nouvelles approches thérapeutiques ciblées du cancer et des maladies rares liées aux mutations non sens. / Nonsense mutations generate premature termination codons (PTC) within an open reading frame. This type of mutation is found in about 11% of patients with genetic disorders. Concerning cancer, 5 to 40% of mutations affecting tumor-suppressing genes are nonsense mutations. The presence of a PTC in a gene leads to rapid degradation of its mRNA mediated by the RNA surveillance mechanism named NMD (Nonsense-mediated mRNA decay) preventing the synthesis of truncated proteins. In cancer, the absence of expression of tumor suppressing genes such as TP53 interferes with many biological pathways including apoptosis enabling tumor progression.A screening system that allows identifying molecules capable of re-expressing genes harboring nonsense mutations by inhibiting the NMD system and/or by activating readthrough has been developed in the lab. Readthrough is a natural mechanism, which occurs during translation, leading to the incorporation of an amino acid at the PTC position. Among the molecules that have been identified thanks to the screen, a natural extract named H7 and a compound named CNSM1 efficiently rescues the expression of the nonsense-mutated TP53 gene carrying a PTC.CNSM1 and H7 induces the expression of full-length proteins from PTC-containing genes indicating that these compounds are capable of activating readthrough. I validated the screen results on several cancer cell lines harboring an endogenous nonsense mutation in TP53 gene and showed that the function of p53 was restored in the presence of CNSM1 or H7. I also investigated the cellular toxicity related with the use of CMNS1 on cultured cells and the in vivo effect of H7 in a mouse model harboring a nonsense mutation in dystrophin gene. My results demonstrate that these compounds have a mild cellular toxicity. In addition, using a genome editing approach I confirmed the relationship between the cytoskeletal blockage and the NMD inhibition. I identified two proteins that are implicated in the cytoskeletal rearrangement, which might be targeted to induce NMD inhibition and then the expression of truncated but functional protein from the mutated mRNA. H7 or CNMS1 might be coupled to an NMD inhibition strategy to improve the nonsense mutation correction. Knowing CNSM1 and H7 are so far the most efficient molecule capable of rescuing the expression of PTC-containing genes, these compounds represents a realistic hope for a new-targeted therapy for pathologies associated with nonsense mutations.

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Consensual Qualitative Research methodology was used to explore how experienced therapists understood and learned from cases of premature termination. Eleven board certified therapists participated in semi-structured interviews concerning a case of a former client who had left treatment prematurely. They offered their reflections on the client’s presentation, the structure of the treatment, successful aspects of the therapy, problems in the treatment, the process of termination, and the impact on their own professional development. Core ideas were identified in each interview, and were cross-referenced to highlight the most common experiences described by the therapists. Premature terminations resulted from multiple, concurrent problems in the treatment including client un-readiness to change, therapist mistakes, and strains in the therapeutic relationship. Therapists experienced a mixture of emotions following the termination including anger, confusion, sadness, and occasional relief. Although therapists initially described premature termination as the result of client issues and psychopathology, upon reflection they acknowledged their own contributions to the premature termination. In the end, therapists remained uncertain about why their former clients left treatment because they lacked their clients’ perspectives. Recommendations for future research and implications for clinical practice are offered.

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Esta tese teve como objetivo geral analisar o fenômeno do abandono em psicoterapia psicanalítica (PP) através de metodologia qualitativa. Para tanto, três artigos foram realizados identificando características de inicio e término de tratamento de pacientes adultos classificados por seus psicoterapeutas como pacientes que abandonaram a PP, em um serviço de atendimento da cidade de Porto Alegre/Brasil, cujo objetivo principal é a formação de especialistas em PP. Foi utilizado em todos os estudos o método de Bardin (1995) para analisar o conteúdo das entrevistas iniciais de tratamento, encontradas no arquivo do serviço de atendimento, e das entrevistas pós-tratamento realizadas pela autora da tese. O primeiro artigo apresenta a análise do tratamento de seis mulheres que abandonaram a PP. Objetivos pouco claros de tratamento, fraca disposição para mudar, sinais precoces de transferência negativa e resistência, e ausência de reconhecimento da própria participação nos problemas são fatores que surgiram no início da psicoterapia. Ganhos terapêuticos, insatisfação e resistência durante o processo psicoterapêutico pareceram estar associados ao abandono. O segundo artigo revela os achados dos tratamentos de cinco pacientes que abandonaram a PP e de cinco que a completaram. Pacientes que abandonaram a PP apresentaram no início do tratamento: objetivos e expectativas focalizadas, fraca disposição para mudar, capacidade de insight diminuída, percepção negativa dos tratamentos anteriores, e manifestações significativas de transferência negativa e resistência. Por outro lado, pacientes que completaram a PP possuíam metas e expectativas de psicoterapia relacionada com aspectos mais amplos da vida, foram menos resistentes para começar o tratamento, apresentaram maior disposição de mudar, transferência mais positiva, e níveis mais elevados de percepção e de satisfação com o tratamento anterior. Durante o tratamento, pacientes que completaram a PP foram menos resistentes e estavam mais satisfeitos com a psicoterapia, referiram benefícios mais eficazes e alcançaram maior capacidade de continuar trabalhando em problemas psicológicos, em comparação com os pacientes que abandonaram a PP. E o terceiro artigo, mostra os dados encontrados nos tratamentos de pacientes que abandonaram a PP em diferentes momentos da psicoterapia. Sete pacientes de tempo de abandono médio (AM- dois a 11 meses após o início da psicoterapia) comparados com sete pacientes de tempo de abandono tardio (AT- mais de um ano após o início) foram identificados como aqueles que iniciaram o tratamento mais por indicação de terceiros do que por conta própria, apresentando maior resistência, com expectativas de mais apoio, menor transferência positiva, mais queixas depressivas e experiências negativas com tratamentos anteriores. Na entrevista pós-tratamento revelaram mais resistência durante o processo de psicoterapia. Abandonaram a psicoterapia com menor capacidade de insight, avaliaram mais negativamente o tratamento tanto nos aspectos gerais como nos específicos. Embora distinções tenham sido observadas, entende-se que a diferenciação das características dos grupos de AM e AT é tênue e necessita de mais investigações. Esta tese oferece algumas hipóteses ou explicações para o complexo fenômeno do abandono da PP. Sugere que as decisões de iniciar, abandonar ou completar a psicoterapia dependem de múltiplos fatores, tais como: definição de metas e objetivos estabelecidos em conjunto pela dupla paciente/psicoterapeuta, disposição para empreender mudanças, capacidade de insight que implica em reconhecimento da condição psíquica e da participação nos problemas, resistência, transferência e experiência vivenciada em tratamento anterior. Os resultados obtidos nesta tese são exploratórios necessitando mais estudos nessa área. / This thesis had as general objective to analyze the phenomenon of dropout in psychoanalytic psychotherapy (PP) through qualitative methodology. To do so, three articles were written identifying characteristics of beginning and end of treatment of adult patients who were classified by their psychotherapists as patients who dropped out the PP, in a service of attendance in the city of Porto Alegre/Brazil, whose main objective is the formation of specialists in PP. The Bardin’s method (1995) was used in all the studies to analyze the content of the initial interviews of treatment, which were found in the file of the attendance service, and of the post-treatment interviews accomplished by the authoress of the thesis. The first article presents the analysis of treatment of six women who dropped out the PP. Factors that came up in the beginning of the psychotherapy were: unclear objectives of the treatment, weak readiness to change, precocious signs of negative transference and resistance and absence of recognition about the own participation in the problems. Therapeutic gains, dissatisfaction and resistance during the therapeutic process seemed to be associated to the dropout. The second article reveals the findings of the treatments of five patients who dropped out the PP and other five who completed it. Patients who dropped out the PP presented in the beginning of the treatment: focalized objectives and expectations, weak disposition to change, decreased capacity for insight, negative perception of the previous treatments and meaningful manifestations of negative transference and resistance. On the other hand, patients who completed the PP had goals and expectations of psychotherapy related to wider aspects of life, were less resistant to begin the treatment, presented a bigger disposition to change, more positive transference and higher levels of perception and satisfaction concerning the previous treatment. During the treatment, patients who completed the PP were less resistant and were more satisfied about the psychotherapy, referred more effective benefits and reached a bigger capacity to continue working in psychological problems if compared to patients who dropped out the PP. And the third article shows the data found in treatments of patients who dropped out the PP in different moments of the therapy. Seven patients of medium time of dropout (MD - two to eleven months after the beginning of the psychotherapy) compared to seven patients of late time of dropout (LD - more than one year after the beginning) were identified as the ones who started the treatment by indication of others more than by their own, presenting more resistance, with expectations of more support, less positive transference, more depressive complains and negative experiences about the previous treatments. In the post-treatment interview they revealed more resistance during the process of psychotherapy. They dropped out the psychotherapy with minor capacity of insight, evaluated the treatment in a more negative way concerning its general aspects as well as the specific ones. Although distinctions have been observed, it is understood that the differentiation of the characteristics of the groups of MD and LD is tenuous and it needs more investigation. This thesis offers some hypothesis or explanations for the complex phenomenon of dropout of PP. It suggests that the decisions about initiate, dropping out, or completing the psychotherapy depend on multiple factors, such as: definition of marks and objectives established in partnership (patient/psychotherapist), disposition to undertake changes, capacity of insight which implies in recognition of the psychic condition and the participation of problems, resistance, transference and experience that were experienced in previous treatment. The results which were obtained in this thesis are exploratory and it is necessary to study more in this area.