Impact of age and race on outcomes of a program to prevent excess weight gain and disordered eating in adolescent girls

Interpersonal psychotherapy (IPT) prevents weight gain and reduces loss-of-control (LOC)-eating in adults. However, IPT was not superior to health-education (HE) for preventing excess weight gain and reducing LOC-eating over 1-year in adolescent girls at risk for excess weight gain and eating disorders. Limited data suggest that older and non-White youth may be especially responsive to IPT. In secondary analyses, we examined if age or race moderated weight and LOC-eating outcomes. The 113 participants (12–17 years; 56.6% White) from the original trial were re-contacted 3 years later for assessment. At baseline and follow-up visits through 3 years, we assessed BMI, adiposity by dual energy X-ray absorptiometry, and LOC-eating presence. In linear mixed models, baseline age moderated 3-year BMI outcome; older girls in IPT had the lowest 3-year BMI gain compared to younger girls in IPT and all girls in HE, p = 0.04. A similar pattern was observed for adiposity. Race moderated 3-year LOC-eating; non-White girls in IPT were most likely to abstain from LOC-eating at 3 years compared to all other girls, p = 0.04. This hypothesis-generating analysis suggests future studies should determine if IPT is especially efficacious at reducing LOC-eating in older, non-White adolescents

Temperament Factors and Dimensional, Latent Bifactor Models of child psychopathology: Transdiagnostic and Specific Associations in Two Youth Samples

Common emotional and behavioral symptoms co-occur and are associated with core temperament factors. This study investigated links between temperament and dimensional, latent psychopathology factors, including a general common psychopathology factor (p factor) and specific latent internalizing and externalizing liabilities, as captured by a bifactor model, in two independent samples of youth. Specifically, we tested the hypothesis that temperament factors of negative affectivity (NA), positive affectivity (PA), and effortful control (EC) could serve as both transdiagnostic and specific risks in relation to recent bifactor models of child psychopathology. Sample 1 included 571 youth (average age 13.6, SD = 2.37, range 9.3–17.5) with both youth and parent report. Sample 2 included 554 preadolescent children (average age 7.7, SD = 1.35, range = 5–11 years) with parent report. Structural equation modeling showed that the latent bifactor models fit in both samples. Replicated in both samples, the p factor was associated with lower EC and higher NA (transdiagnostic risks). Several specific risks replicated in both samples after controlling for co-occurring symptoms via the p factor: internalizing was associated with higher NA and lower PA, lower EC related to externalizing problems

Personalized Depression Prevention: A Randomized Controlled Trial to Optimize Effects Through Risk-Informed Personalization

Objective: To evaluate whether evidence-based depression prevention programs can be optimized by matching youths to interventions that address their psychosocial vulnerabilities. Method: This randomized controlled trial included 204 adolescents (mean [SD] age ¼ 14.26 [1.65] years; 56.4% female). Youths were categorized as high or low on cognitive and interpersonal risks for depression and randomly assigned to Coping With Stress (CWS), a cognitive-behavioral program, or Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST), an interpersonal program. Some participants received a match between risk and prevention (eg, high cognitive–low interpersonal risk teen in CWS, low cognitive–high interpersonal risk teen in IPT-AST), others received a mismatch (eg, low cognitive-high interpersonal risk teen in CWS). Outcomes were depression diagnoses and symptoms through 18 months postintervention (21 months total). Results: Matched adolescents showed significantly greater decreases in depressive symptoms than mismatched adolescents from postintervention through 18-month follow-up and across the entire 21-month study period (effect size [d] ¼ 0.44, 95% CI ¼ 0.02, 0.86). There was no significant difference in rates of depressive disorders among matched adolescents compared with mismatched adolescents (12.0% versus 18.3%, t193 ¼ .78, p ¼ .44). Conclusion: This study illustrates one approach to personalizing depression prevention as a form of precision mental health. Findings suggest that risk-informed personalization may enhance effects beyond a one-size-fits-all approach. Clinical trial registration information: Bending Adolescent Depression Trajectories Through Personalized Prevention; https://www.clinicaltrials. gov/; NCT01948167

IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu ) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism

Implementing nudges for suicide prevention in real-world environments: project INSPIRE study protocol

Background: Suicide is a global health issue. There are a number of evidence-based practices for suicide screening, assessment, and intervention that are not routinely deployed in usual care settings. The goal of this study is to develop and test implementation strategies to facilitate evidence-based suicide screening, assessment, and intervention in two settings where individuals at risk for suicide are especially likely to present: primary care and specialty mental health care. We will leverage methods from behavioral economics, which involves understanding the many factors that influence human decision making, to inform strategy development. Methods: We will identify key mechanisms that limit implementation of evidence-based suicide screening, assessment, and intervention practices in primary care and specialty mental health through contextual inquiry involving behavioral health and primary care clinicians. Second, we will use contextual inquiry results to systematically design a menu of behavioral economics-informed implementation strategies that cut across settings, in collaboration with an advisory board composed of key stakeholders (i.e., behavioral economists, clinicians, implementation scientists, and suicide prevention experts). Finally, we will conduct rapid-cycle trials to test and refine the menu of implementation strategies. Primary outcomes include clinician-reported feasibility and acceptability of the implementation strategies. Discussion: Findings will elucidate ways to address common and unique barriers to evidence-based suicide screening, assessment, and intervention practices in primary care and specialty mental health care. Results will yield refined, pragmatically tested strategies that can inform larger confirmatory trials to combat the growing public health crisis of suicide

Links between Within-person Fluctuations in Hyperactivity/attention Problems and Subsequent Conduct Problems

Background: The onset of hyperactivity/impulsivity and attention problems (HAP) is typically younger than that of conduct problems (CP), and some research supports a directional relation wherein HAP precedes CP. Studies have tested this theory using between-person and between-group comparisons, with conflicting results. In contrast, prior research has not examined the effects of within-person fluctuations in HAP on CP. Method: This study tested the hypothesis that within-person variation in HAP would positively predict subsequent within-person variation in CP, in two population samples of youth (N = 620) who participated in identical methods of assessment over the course of 30 months. Three-level, hierarchical models were used to test for within-person, longitudinal associations between HAP and CP, as well as moderating effects of between-person and between-family demographics. Results: We found a small but significant association in the expected direction for older youth, but the opposite effect in younger and non-Caucasian youth. These results were replicated across both samples. Conclusions: The process by which early HAP relates to later CP may vary by age and racial identity

Cortisol reactivity to stress among youth: Stability over time and genetic variants for stress sensitivity.

Stress sensitivity may be one process that can explain why some genetically at-risk individuals are more susceptible to some types of stress-reactive psychopathologies. Dysregulation of the Limbic Hypothalamic Pituitary Adrenal (LHPA) axis, including cortisol reactivity to challenge, represents a key aspect of stress sensitivity. However, the degree of stability over time among youth, especially differential stability as a function of particular genetic variants, has not been investigated. A general community sample of children and adolescents (mean age = 11.4; 56% girls) provided a DNA sample and completed two separate laboratory stress challenges, across an 18-month follow-up (N =224 at Time 1; N = 194 at Time 2), with repeated measures of salivary cortisol. Results showed that test-retest stability for several indices of cortisol reactivity across the laboratory challenge visits were significant and of moderate magnitude for the whole sample. Moreover, gene variants of several biologically plausible systems relevant for stress sensitivity (especially 5-HTTLPR and CRHR1) demonstrated differential stability of cortisol reactivity over 18-months, such that carriers of genotypes conferring enhanced environmental susceptibility exhibited greater stability of cortisol levels over time for some LHPA axis indices. Findings suggest that LHPA axis dysregulation may exhibit some trait-like aspects underlying stress sensitivity in youth, especially for those who carry genes related to greater genetic susceptibility to environmental stress