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

Effect of a Cognitive-Behavioral Prevention Program on Depression 6 Years After Implementation Among At-Risk Adolescents: A Randomized Clinical Trial.

IMPORTANCE: Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent depression and functioning are not known. OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program reduced the incidence of depressive episodes, increased depression-free days, and improved developmental competence 6 years after implementation. DESIGN, SETTING, AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP plus usual care vs usual care, through follow-up 75 months after the intervention (88% retention), with recruitment from August 2003 through February 2006 at a health maintenance organization, university medical centers, and a community mental health center. A total of 316 participants were 13 to 17 years of age at enrollment and had at least 1 parent with current or prior depressive episodes. Participants could not be in a current depressive episode but had to have subsyndromal depressive symptoms or a prior depressive episode currently in remission. Analysis was conducted between August 2014 and June 2015. INTERVENTIONS: The CBP program consisted of 8 weekly 90-minute group sessions followed by 6 monthly continuation sessions. Usual care consisted of any family-initiated mental health treatment. MAIN OUTCOMES AND MEASURES: The Depression Symptoms Rating scale was used to assess the primary outcome, new onsets of depressive episodes, and to calculate depression-free days. A modified Status Questionnaire assessed developmental competence (eg, academic or interpersonal) in young adulthood. RESULTS: Over the 75-month follow-up, youths assigned to CBP had a lower incidence of depression, adjusting for current parental depression at enrollment, site, and all interactions (hazard ratio, 0.71 [95% CI, 0.53-0.96]). The CBP program\u27s overall significant effect was driven by a lower incidence of depressive episodes during the first 9 months after enrollment. The CBP program\u27s benefit was seen in youths whose index parent was not depressed at enrollment, on depression incidence (hazard ratio, 0.54 [95% CI, 0.36-0.81]), depression-free days (d = 0.34, P = .01), and developmental competence (d = 0.36, P = .04); these effects on developmental competence were mediated via the CBP program\u27s effect on depression-free days. CONCLUSIONS AND RELEVANCE: The effect of CBP on new onsets of depression was strongest early and was maintained throughout the follow-up period; developmental competence was positively affected 6 years later. The effectiveness of CBP may be enhanced by additional booster sessions and concomitant treatment of parental depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00073671

An internet-based adolescent depression preventive intervention: study protocol for a randomized control trial

Background: The high prevalence of major depressive disorder in adolescents and the low rate of successful treatment highlight a pressing need for accessible, affordable adolescent depression prevention programs. The Internet offers opportunities to provide adolescents with high quality, evidence-based programs without burdening or creating new care delivery systems. Internet-based interventions hold promise, but further research is needed to explore the efficacy of these approaches and ways of integrating emerging technologies for behavioral health into the primary care system. Methods/Design We developed a primary care Internet-based depression prevention intervention, Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training (CATCH-IT), to evaluate a self-guided, online approach to depression prevention and are conducting a randomized clinical trial comparing CATCH-IT to a general health education Internet intervention. This article documents the research framework and randomized clinical trial design used to evaluate CATCH-IT for adolescents, in order to inform future work in Internet-based adolescent prevention programs. The rationale for this trial is introduced, the current status of the study is reviewed, and potential implications and future directions are discussed. Discussion The current protocol represents the only current, systematic approach to connecting at-risk youth with self-directed depression prevention programs in a medical setting. This trial undertakes the complex public health task of identifying at-risk individuals through mass screening of the general primary care population, rather than solely relying on volunteers recruited over the Internet, and the trial design provides measures of both symptomatic and diagnostic clinical outcomes. At the present time, we have enrolled N = 234 adolescents/expected 400 and N = 186 parents/expected 400 in this trial, from N = 6 major health systems. The protocol described here provides a model for a new generation of interventions that blend substantial computer-based instruction with human contact to intervene to prevent mental disorders such as depression. Because of the potential for broad generalizability of this model, the results of this study are important, as they will help develop the guidelines for preventive interventions with youth at-risk for the development of depressive and other mental disorders. Trial registration Clinical Trial Registry: NCT01893749 date 6 May 2012