The Role of Vitamin D and Vitamin D Receptor in Immunity to Leishmania major Infection

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreased Leishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance to L. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance to L. major infection but only in a host that is predisposed for Th-1 immune responses

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

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-D10) 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-D10 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-D10 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. Trial Registration ClinicalTrials.gov Identifier: NCT0189374

Prevention of Adolescent Depression in Primary Care: Barriers and Relational Work Solutions

Background and Purpose: Depression affects millions of adolescents in the United States each year. This population may benefit from targeted preventive interventions. We sought to understand the internal factors that affect the ability of healthcare organizations to implement an intervention that involves mental health screening and depression prevention treatment of at-risk adolescents in primary care settings. Methods: From November 2011 to July 2016 we conducted a study of the implementation of a multisite (N=30) phase 3 randomized clinical trial of an Internet-based depression prevention intervention program (CATCH-IT). We describe the prevalence of internal barriers on the screening and enrollment process by reporting REACH (the proportion of target audience exposed to the intervention). Results: A total of 369 adolescents were randomized into the intervention or control program. Mean REACH values for the study clinics were 0.216 for screening and 0.181 for enrollment to CATCH-IT. Mean REACH enrollment lost due to internal barriers was 0.233. This translated to 4,691 adolescents lost at screening and 2,443 adolescents lost at enrollment due to internal barriers. Conclusion: We propose a model of the implementation process that emphasizes the importance of positive relational work that assists in overcoming internal barriers to REACH. We also provide implications for policy and practice

Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults

Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections.In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009-2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill.Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese

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