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Although research supports cognitive behaviour therapy (CBT) as the treatment of choice for childhood obsessive compulsive disorder (OCD) and recommends family involvement (e.g., AACAP, 1998; Barrett, Healey-Farrell, & March, 2004a), little is known about the role of the family in the development, maintenance, and treatment of childhood OCD. Furthermore, although significant improvements are found in treatment response, many children remain symptomatic (de Haan, 2006). Objective: The aims of the study were to examine (1) the perceptions of the family environment among family members and if child perceptions change with treatment and (2) treatment response and child and family characteristics that may predict treatment response. Gender differences were also examined. Method: This study involved 82 children (ages 8 to 17 years) receiving CBT for OCD and a concurrent parent program. Children and parents were assessed at initial, pre-, and post-treatment with questionnaires, a symptom severity interview, a family environment questionnaire, and child self-report measures of anxiety and depression. Pre-treatment data were used for the prediction of treatment response. Results: Child and parent perceptions of the family environment differ in terms of family expressiveness, with children perceiving their family as being ‘distressed.’ Although girls and boys had similar perceptions of their family environment, girls’ perceptions were more in agreement with their parents than boys. Children’s ratings of family cohesiveness were ‘normal’ at pre-treatment, and increased significantly at post-treatment; however, this was not meaningful when gender was considered. We found a similar treatment response to past research. Different characteristics were found to predict treatment response for boys and girls, with more predictors being identified for girls. Conclusions: Results emphasize the importance that families may have in the treatment of OCD and in our attempt to find predictors, as well as the need to examine boys and girls separately. This research is critical to refine and tailor treatment techniques to match child and family characteristics.

Although research supports cognitive behaviour therapy (CBT) as the treatment of choice for childhood obsessive compulsive disorder (OCD) and recommends family involvement (e.g., AACAP, 1998; Barrett, Healey-Farrell, & March, 2004a), little is known about the role of the family in the development, maintenance, and treatment of childhood OCD. Furthermore, although significant improvements are found in treatment response, many children remain symptomatic (de Haan, 2006). Objective: The aims of the study were to examine (1) the perceptions of the family environment among family members and if child perceptions change with treatment and (2) treatment response and child and family characteristics that may predict treatment response. Gender differences were also examined. Method: This study involved 82 children (ages 8 to 17 years) receiving CBT for OCD and a concurrent parent program. Children and parents were assessed at initial, pre-, and post-treatment with questionnaires, a symptom severity interview, a family environment questionnaire, and child self-report measures of anxiety and depression. Pre-treatment data were used for the prediction of treatment response. Results: Child and parent perceptions of the family environment differ in terms of family expressiveness, with children perceiving their family as being ‘distressed.’ Although girls and boys had similar perceptions of their family environment, girls’ perceptions were more in agreement with their parents than boys. Children’s ratings of family cohesiveness were ‘normal’ at pre-treatment, and increased significantly at post-treatment; however, this was not meaningful when gender was considered. We found a similar treatment response to past research. Different characteristics were found to predict treatment response for boys and girls, with more predictors being identified for girls. Conclusions: Results emphasize the importance that families may have in the treatment of OCD and in our attempt to find predictors, as well as the need to examine boys and girls separately. This research is critical to refine and tailor treatment techniques to match child and family characteristics.

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.

Borderline personality disorder (BPD) is a complex psychiatric condition whose severity is compounded by the heterogeneous psychological functioning of those who suffer from the disorder. This heterogeneity has made the identification of a unified treatment strategy difficult and attempts to resolve this variation within the disorder by investigating subtypes of BPD have been made. However, the clinical utility of this approach has not been examined. The major object of this research project was to investigate the presence of subtypes of BPD and to examine whether treatment effectiveness varied as a function of subtype. Data from 61, predominantly female, participants with BPD were entered into a cluster analysis. Using variables that are central to cognitive behavioural models of BPD and have been shown to be heterogeneously distributed in previous BPD samples, two subgroups were identified and defined on the basis of whether participants attributed the causes o f negative events as being themselves or other people. Consistent with hypotheses, the subgroup with a tendency to blame others for negative events showed far lower levels of change between admission and discharge than the subgroup who blamed themselves for negative events, on both measures of statistical and clinical significance. Alternate means of identifying participants who optimally responded to the intervention were explored and a cluster analysis identified two groups of participants that were separated on the basis of whether they had shown clinically significant change on a range of variables. It was found that data from admission to the program could successfully predict which participants would belong in the optimal or mixed response groups upon discharge. Taken together, the findings of this research project suggest that not only can theoretically valid subgroups of BPD be identified, but that they have clinical utility in understanding participants' response to intervention. Further, the findi ngs suggest that profiles of clinical change can be identified and predicted. The findings of this research project are discussed with respect to their methodological limitations, suggestions for future research, and their implications for both theory and practice.

Background: Rheumatoid arthritis (RA) is a common complex autoimmune disorder which is influenced by both genetic and environmental factors. While multiple factors that influence susceptibility to and outcome of disease have been identified there is still a large proportion of missing heritability and limited understanding of disease pathogenesis. In recent years, biologic drug therapies have advanced treatment of RA; however good disease control is achieved in just 30% of patients, making identification of predictors of treatment response important. One area of research which is yet to be explored in relation to treatment response, and requires further evaluation in RA susceptibility, is epigenetics. Epigenetics is the study of modifications of the DNA which can influence gene expression but do not alter genetic sequence, and the most commonly studied epigenetic phenomenon, to date, is DNA methylation. Objectives: To identify DNA methylation signatures predictive of treatment response to anti-TNF biologics, to explore the role of DNA methylation in RA susceptibility using disease discordant monozygotic (MZ) twins, and to assess the effect of cryopreservation of cells on DNA methylation. Methods: Genome-wide DNA methylation levels were measured using the HumanMethylation450 BeadChip in pre-treatment whole blood DNA samples from individuals who had extremely good or extremely poor response to the anti-TNF therapies, etanercept and adalimumab, and in MZ twins discordant for RA (n=79 pairs). I also compared genome-wide methylation in cells which had been cryopreserved with fresh cells, to investigate if this technique is suitable for epigenetic investigations. Results: I identified four methylation sites which were significantly related to response to etanercept at a false discovery rate of 5%, the most significantly differentially methylated of which maps to the LRPAP1 gene (p=1.46E-8). Indeed, four other sites at the same locus also showed evidence for differential methylation indicating that this represents a differentially methylated region. No sites were significantly associated with response to adalimumab after correction for multiple testing. I identified subtle differences in DNA methylation between RA discordant twins. Although these were not statistically significant following adjustment for cell composition, one of the most differentially methylated positions mapped to the ZNF74 gene (p=4.97E-6), and replicated a methylation difference identified in the largest previous epigenome-wide association study of RA cases and unrelated healthy controls. I found that cryopreservation of cells does not significantly alter the methylome, an important observation that will impact upon design of future studies. Conclusions: In the largest studies of DNA methylation in RA treatment response and RA discordant MZ twins to date, I identified significant differential methylation in etanercept response, but not adalimumab response, and found small differences in methylation in RA discordant MZ twins. I also concluded that cryopreservation does not significantly alter the methylome.

BACKGROUND: Soft neurological signs (SNS) are subtle, nonspecific neurological abnormalities that are present in first episode psychosis (FEP) patients. SNS are associated with clinical variables such as poor long term psychosocial functioning, executive functioning, and positive and negative symptomology. However, few studies have evaluated treatment responsiveness with respect to SNS. OBJECTIVE: To investigate whether SNS show: 1.) baseline and longitudinal differences between both diagnostic groups (schizophrenia (FEP-SZ), non-schizophrenia FEP-NSZ, and healthy controls (HC)) and treatment outcome (week 26 and year 1); 2.) relationships to clinical measures; 3.) predictive characteristics of treatment response. METHODS: SNS scores (Neurological Evaluation Scale) were obtained for 312 FEP (236 FEP-SZ and 76 FEP-NSZ subjects and 169 HC subjects and for subjects classified as treatment responsive and non-responsive at week 26 (N=105, N=105) and year 1 (N=101, N=97), respectively. Diagnostic group and treatment responsiveness group comparisons were assessed with ANCOVA and logistic regression models and both were co-varied for age, sex, race, and handedness. Baseline and longitudinal SNS relationships to clinical variables were determined using Spearman correlations and repeated measures correlations, and both were corrected by False Discovery Rate. Linear mixed effects model was utilized to analyze the data longitudinally. RESULTS: Baseline cognitive perceptual SNS measures had the greatest effect size differences, were predictive of group membership, and differentiated the two proband groups with FEP-SZ having worse SNS scores. Baseline cognitive perceptual SNS did not significantly predict treatment response at week 26 or year 1, but changes in cognitive perceptual at week 26 was predictive of treatment responsiveness at week 26 and year 1. Longitudinally, SNS scores drop in both FEP groups and treatment groups. The FEP-SZ group showed greater longitudinal within subject correlations than FEP-NSZ. SNS scores were only differentiated between year 1 outcome groups at week 8. There were greater longitudinal within subject correlations for the responsive group. CONCLUSION: Our findings indicate that there are baseline group differences and that changes in cognitive perceptual SNS scores at week 26 are predictive of treatment responsiveness at week 26 and year 1. / 2019-07-03T00:00:00Z

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