Increasing Understanding in Children of Depressed Parents: Predictors and Moderators of Intervention Response

We evaluated predictors and moderators of differential response to two family-based depression prevention programs for families with a depressed parent: a clinician-facilitated intervention and a lecture group intervention. Individual and family level variables were examined using regression analyses with generalized estimating equations. For the outcome of child understanding of depression, parental changes in child-related behaviors and attitudes predicted greater child understanding ( < 0.001). For the parent outcome of behavior and attitude change, across intervention conditions, younger parent age ( < 0.05), female parent gender ( < 0.01), more chronic and severe parental depression history ( < 0.05), lower SES ( < 0.05), and single-parent status ( < 0.05) were associated with better outcomes across conditions. Effect sizes were moderate, ranging from 0.4 to 0.7 SD. Family and marital functioning were not found to be predictors of any outcomes. When both parents were depressed at baseline, there was no difference in the clinician-versus lecture-based approach, and when only the father was depressed, families reported more changes with the clinician condition than with the lecture condition ( < 0.05). Findings from this study can help identify intervention strategies that are appropriate for different types of at-risk individuals and families

Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care

Importance: Although 13% to 20% of American adolescents experience a depressive episode annually, no scalable primary care model for adolescent depression prevention is currently available. Objective: To study whether competent adulthood transition with cognitive behavioral humanistic and interpersonal training (CATCH-IT) lowers the hazard for depression in at-risk adolescents identified in primary care, as compared with a general health education (HE) attention control. Design, Setting, and Participants: This multicenter, randomized clinical trial, a phase 3 single-blind study, compares CATCH-IT with HE. Participants were enrolled from 2012 to 2016 and assessed at 2, 6, 12, 18, and 24 months postrandomization in a primary care setting. Eligible adolescents were aged 13 to 18 years with subsyndromal depression and/or history of depression and no current depression diagnosis or treatment. Of 2250 adolescents screened for eligibility, 446 participants completed the baseline interview, and 369 were randomized into CATCH-IT (n = 193) and HE (n = 176). Interventions: The internet-based intervention, CATCH-IT, is a 20-module (15 adolescent modules and 5 parent modules) online psychoeducation course that includes a parent program, supported by 3 motivational interviews. Main Outcomes and Measures: Time to event for depressive episode; depressive symptoms at 6 months. Results: Of 369 participants (mean [SD] age, 15.4 [1.5] years; 251 women [68%]) included in this trial, 193 were randomized into CATCH-IT and 176 into HE. Among these participants, 28% had both a past episode and subsyndromal depression; 12% had a past episode only, 59% had subsyndromal depression only, and 1% had borderline subsyndromal depression. The outcome of time to event favored CATCH-IT but was not significant with intention-to-treat analyses (unadjusted hazard ratio [HR], 0.59; 95% CI, 0.27-1.29; P = .18; adjusted HR, 0.53; 95% CI, 0.23-1.23; P = .14). Adolescents with higher baseline Center for Epidemiologic Studies Depression scale (CES-D ) scores showed a significantly stronger effect of CATCH-IT on time to event relative to those with lower baseline scores (HR 0.82; 95% CI, 0.67-0.99; P = .04). For example, the hazard ratio for a CES-D score of 15 was 0.20 (95% CI, 0.05-0.77), compared with a hazard ratio of 1.44 (95% CI, 0.41-5.03) for a CES-D score of 5. In both CATCH-IT and HE groups, depression symptoms declined and functional scores increased. Conclusions and Relevance: For preventing depressive episodes CATCH-IT may be better than HE for at-risk adolescents with subsyndromal depression. Also CATCH-IT may be a scalable approach to prevent depressive episodes in adolescents in primary care

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Transition to Adulthood in Children of Depressed Parents: Long-Term Follow-Up Data from the Family Talk Preventive Intervention Project

Little is known about the effects of parental depression on offspring as they transition to adulthood—a challenging time developmentally, when late adolescents must separate from home, achieve intimate relationships, and develop a sense of identity. We present long-term quantitative and qualitative data from early adolescents with a depressed parent who were randomized to one of two family-based preventive interventions and followed over time, across the transition to young adulthood. Specifically, we present clinical measures of psychopathology and Likert-scale questionnaire data from young adults and their parents regarding the transition to adulthood and perceptions of the interventions. We also report in-depth qualitative interview data from young adults about the effects of parental depression on their transition to adulthood. Findings suggest that leaving home, establishing relationships, and coping with stressors may be challenging for emerging adults. Furthermore, the interviews highlight the importance of siblings, the burden of parental depression, and the development of self-understanding and empathy in young adults who grew up with a depressed parent. Data suggest that clinicians, policy makers, educators, and employers must address the preventive and clinical needs of young people and their families as they transition to young adulthood after growing up with depressed parents

Increasing Understanding in Children of Depressed Parents: Predictors and Moderators of Intervention Response

We evaluated predictors and moderators of differential response to two family-based depression prevention programs for families with a depressed parent: a clinician-facilitated intervention and a lecture group intervention. Individual and family level variables were examined using regression analyses with generalized estimating equations. For the outcome of child understanding of depression, parental changes in child-related behaviors and attitudes predicted greater child understanding (p<0.001). For the parent outcome of behavior and attitude change, across intervention conditions, younger parent age (p<0.05), female parent gender (p<0.01), more chronic and severe parental depression history (p<0.05), lower SES (p<0.05), and single-parent status (p<0.05) were associated with better outcomes across conditions. Effect sizes were moderate, ranging from 0.4 to 0.7 SD. Family and marital functioning were not found to be predictors of any outcomes. When both parents were depressed at baseline, there was no difference in the clinician- versus lecture-based approach, and when only the father was depressed, families reported more changes with the clinician condition than with the lecture condition (p<0.05). Findings from this study can help identify intervention strategies that are appropriate for different types of at-risk individuals and families

The feasibility and acceptability of a preventive intervention programme for children with depressed parents:study protocol for a randomised controlled trial

BACKGROUND: One of the most important risk factors for childhood depression is being the child of a depressed parent. These at-risk children have two to four times the probability of having an affective episode compared with their peers. Preventive interventions such as Beardslee’s Preventive Intervention Program (PIP) that are targeted at children of depressed parents have proven effective in many countries. The PIP is a family-based approach that works by promoting resilience in children and increasing positive interactions within the family. In this pilot randomised controlled trial (RCT), we will determine the acceptability and feasibility of an adapted version of this intervention in Chile. METHODS/DESIGN: We are conducting a pilot RCT with a manualized intervention. The intervention will be delivered in seven weekly sessions at the family home. It is targeted mostly at parents but will also measure outcomes among the children. Control subjects will follow their treatment as usual. Feasibility and acceptability will be assessed by recruitment, adherence, dropout and level of missing data, as well as the burden of scales and measurement tools. Families will be followed for 11 months. DISCUSSION: Given the negative lifelong consequences of depression and the burden they represent, preventive programmes are not only feasible but necessary. Despite the successful implementation of this intervention in different countries, an adaptation to the Chilean reality will be prerequisite. The results of this pilot study will inform a definitive trial that will make the case for its national implementation. TRIAL REGISTRATION: Clinicaltrials.gov trial identifier: NCT02593266. Registration date: 30 Octo 2015