Views of young people in rural Australia on SPARX, a fantasy world developed for New Zealand youth with depression.

Background: A randomized control trial demonstrated that a computerized cognitive behavioral therapy (cCBT) program (Smart, Positive, Active, Realistic, X-factor thoughts [SPARX]) was an appealing and efficacious treatment for depression for adolescents in New Zealand. Little is known about the acceptability of computerized therapy programs for rural Australians and the suitability of computerized programs developed in one cultural context when used in another country. Issues such as accents and local differences in health care access might mean adjustments to programs are required. Objective: This study sought to explore the acceptability of SPARX by youth in rural Australia and to explore whether and how young people would wish to access such a program. Methods: Focus groups and semistructured interviews were conducted with 16 young people attending two youth-focused community services in a small, rural Tasmanian town. An inductive data-driven approach was used to identify themes using the interview transcripts as the primary data source. Interpretation was supported by demographic data, observer notes, and content analysis. Results: Participants reported that young people want help for mental health issues but they have an even stronger need for controlling how they access services. In particular, they considered protecting their privacy in their small community to be paramount. Participants thought computerized therapy was a promising way to increase access to treatment for youth in rural and remote areas if offered with or without therapist support and via settings other than school. The design features of SPARX that were perceived to be useful, included the narrative structure of the program, the use of different characters, the personalization of an avatar, “socialization” with the Guide character, optional journaling, and the use of encouraging feedback. Participants did not consider (New Zealand) accents off-putting. Young people believed the SPARX program would appeal to those who play computer games generally, but may be less appealing for those who do not. Conclusions: The findings suggest that computerized therapy offered in ways that support privacy and choice can improve access to treatment for rural youth. Foreign accents and style may not be off-putting to teenage users when the program uses a playful fantasy genre, as it is consistent with their expectation of fantasy worlds, and it is in a medium with which they already have a level of competence. Rather, issues of engaging design and confidential access appeared to be more important. These findings suggest a proven tool once formally assessed at a local level can be adopted cross-nationally

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

<p>Abstract</p> <p>Objective</p> <p>To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.</p> <p>Methods</p> <p>Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described.</p> <p>Results</p> <p>CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance.</p> <p>Conclusions</p> <p>CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00052078.</p

Indicated school-based intervention to improve depressive symptoms among at risk Chilean adolescents: a randomized controlled trial

Background: Depression is a disabling condition affecting people of all ages, but generally starting during adolescence. Schools seem to be an excellent setting where preventive interventions may be delivered. This study aimed to test the effectiveness of an indicated school-based intervention to reduce depressive symptoms among at-risk adolescents from low-income families. Methods: A two-arm, parallel, randomized controlled trial was conducted in 11 secondary schools in vulnerable socioeconomic areas in Santiago, Chile. High-risk students in year 10 (2° Medio) were invited to a baseline assessment (n = 1048). Those who scored ≥10 (boys) and ≥15 (girls) in the BDI-II were invited to the trial (n = 376). A total of 342 students consented and were randomly allocated into an intervention or a control arm in a ratio of 2:1. The intervention consisted of 8 group sessions of 45 min each, based on cognitive-behavioural models and delivered by two trained psychologists in the schools. Primary (BDI-II) and secondary outcomes (measures of anxiety, automatic thoughts and problem-solving skills) were administered before and at 3 months post intervention. The primary outcome was the recovery rate, defined as the proportion of participants who scored in the BDI-II <10 (among boys) and <15 (among girls) at 3 months after completing the intervention. Results: There were 229 participants in the intervention group and 113 in the control group. At 3-month follow-up 81.4 % in the intervention and 81.7 % in the control group provided outcome data. The recovery rate was 10 % higher in the intervention (50.3 %) than in the control (40.2 %) group; with an adjusted OR = 1.62 (95 % CI: 0.95 to 2.77) (p = 0.08). No difference between groups was found in any of the secondary outcomes. Secondary analyses revealed an interaction between group and baseline BDI-II score. Conclusions: We found no clear evidence of the effectiveness of a brief, indicated school-based intervention based on cognitive-behavioural models on reducing depressive symptoms among Chilean adolescents from low-income families. More research is needed in order to find better solutions to prevent depression among adolescents

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3

Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD

Th1 Disabled Function in Response to TLR4 Stimulation of Monocyte-Derived DC from Patients Chronically-Infected by Hepatitis C Virus

Background: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC) function has thus been suspected, but this remains a controversial issue. Methods and Findings: Here we show that monocyte-derived DC (MoDC) from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNc secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNc secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1b. Addition of MIP-1b on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1b secretion by HCV monocytes participates in the Th1 defect of DC. Conclusions: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. Thi

Predictors of Treatment Attrition Among an Outpatient Clinic Sample of Youths With Clinically Significant Anxiety

Predictors of treatment attrition were examined in a sample of 197 youths (ages 5–18) with clinically-significant symptoms of anxiety seeking psychotherapy services at a community-based outpatient mental health clinic (OMHC). Two related definitions of attrition were considered: (a) clinician-rated dropout (CR), and (b) CR dropout qualified by phase of treatment (pre, early, or late phases) (PT). Across both definitions, rates of attrition in the OMHC sample were higher than those for anxious youths treated in randomized controlled trials, and comorbid depression symptoms predicted dropout, with a higher rate of depressed youths dropping out later in treatment (after 6 sessions). Using the PT definition, minority status also predicted attrition, with more African-American youths lost pre-treatment. Other demographic (age, gender, single parent status) and clinical (externalizing symptoms, anxiety severity) characteristics were not significantly associated with attrition using either definition. Implications for services for anxious youths in public service settings are discussed. Results highlight the important role of comorbid depression in the treatment of anxious youth and the potential value of targeted retention efforts for ethnic minority families early in the treatment process

School-based intervention to improve the mental health of low-income, secondary school students in Santiago, Chile (YPSA): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression is common and can have devastating effects on the life of adolescents. Psychological interventions are the first-line for treating or preventing depression among adolescents. This proposal aims to evaluate a school-based, universal psychological intervention to reduce depressive symptoms among student's aged 13-14 attending municipal state secondary schools in Santiago, Chile.</p> <p>Study design</p> <p>This is a cluster randomised controlled trial with schools as the main clusters. We compared this intervention with a control group in a study involving 22 schools, 66 classes and approximately 2,600 students. Students in the active schools attended 11 weekly and 3 booster sessions of an intervention based on cognitive-behavioural models. The control schools received their usual but enhanced counselling sessions currently included in their curriculum. Mean depression scores and indicators of levels of functioning were assessed at 3 and 12 months after the completion of the intervention in order to assess the effectiveness of the intervention. Direct and indirect costs were measured in both groups to assess the cost-effectiveness of this intervention.</p> <p>Discussion</p> <p>As far as we are aware this is the first cluster randomised controlled trial of a school intervention for depression among adolescents outside the Western world.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN19466209">ISRCTN19466209</a></p