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Introduction: The CDC established the National Diabetes Prevention Program (NDPP) initiative in 2010, leading to implementation of numerous group-based lifestyle interventions, such as the 12-month Group Lifestyle Balance (GLB) program, in community and clinical settings. Heterogeneity in weight outcomes is common. While evidence suggests that session attendance is associated with greater weight loss, some participants do not achieve weight loss even with high session attendance. Conversely, some may achieve clinically significant weight loss (≥5%) with lower attendance. In this study, we sought to identify and characterize such paradoxical interventional outcomes. (i.e., high session attendance and Hypothesis: No a priori hypotheses. Methods: We conducted a longitudinal descriptive analysis of overweight/obese GLB participants using electronic health record data from an integrated healthcare delivery system in Northern California (2010-2017). We focused on the 12-week intensive core phase of the curriculum because prior studies show that weight loss outcomes achieved during this period are highly correlated with long-term weight loss. We categorized patients into 4 mutually exclusive groups by session attendance ( Results: Among 1,818 evaluable participants, we identified 870 (47.9%) with paradoxical outcomes. Of these, 104 (12.0%) achieved ≥5% weight loss with Conclusions: Nearly half of all GLB participants in this integrated health system had paradoxical outcomes, with more than 40% classified as paradoxical non-responders. These results suggest that session attendance may not be as sensitive a predictor of weight outcomes as previously thought, and other approaches are needed to understand the complex factors influencing goal attainment in behavioral lifestyle programs.

Introduction: Obesity and depression often co-occur, especially in women. Efficacious treatments exist for both conditions, but treatment outcomes vary. Assessing sex-specific responses to integrated therapy of these conditions could inform opportunities for tailoring. Hypothesis: Sex will significantly moderate the effects of an integrated collaborative care intervention on weight loss and depression outcomes through 24 months. Short-term treatment response at 6 months will reliably predict 12- and 24-month outcomes by sex. Methods: We conducted secondary analyses using data from the RAINBOW trial, which demonstrated efficacy of an integrated collaborative care intervention at reducing weight (BMI) and depression severity (SCL-20) at 12 months relative to usual care in adults with obesity and depression. Linear mixed models were used to assess treatment effects by sex, an a priori hypothesized biological moderator, on BMI and SCL-20 at 6, 12, and 24 months. Areas under the receiver operating characteristic curves (AUCs) based on logistic regressions were used to assess sex-specific thresholds of weight loss (%) and SCL-20 reduction at 6 months that reliably predicted clinically significant weight loss (i.e., ≥5% of baseline weight) and depression response (i.e., ≥50% decrease in SCL-20 scores) at 12 and 24 months. Results: Sex significantly moderated the treatment effects on BMI and SCL-20. Compared with women, men achieved significantly greater reductions in BMI at 6, 12, and 24 months in the intervention relative to usual care. Compared with men, women achieved significantly greater reductions in SCL-20 at 12 months only in the intervention relative to usual care. AUCs in the logistic models were similar for both sexes: >0.82 at 12 months and >0.65 at 24 months predicting clinically significant weight loss; >0.70 at 12 months and >0.67 at 24 months predicting clinically significant depression response. With 80% specificity to ensure good probability of correctly identifying participants not achieving longer-term outcomes of clinical significance, women who lost 2.5-3.0% weight and men who lost 3.4-4.1% weight at 6 months were likely to achieve ≥5% weight loss at 12 and 24 months. Similarly, women who reduced SCL-20 by 0.70 and men who reduced by 0.60-0.65 were likely to achieve ≥50% decrease in SCL-20 at 12 and 24 months. Conclusions: The treatment effects of this integrated intervention for obesity and depression differed significantly by sex, with men showing greater weight loss and women showing greater depression reduction. Sex-specific short-term responses at 6 months were identified for predicting clinically significant weight loss and depression outcomes at 12 and 24 months. Results suggest that sex may be an important tailoring variable when designing collaborative care interventions.

Introduction: Neural mechanisms underlying behavior therapy in obesity are poorly understood, particularly in patients with comorbid depression. Putative targets include neural circuits for conscious and nonconscious emotion regulation. Hypothesis: Changes in a priori neural circuits for emotion regulation from baseline (0) to 2 mo (mediators, M) mediate changes in BMI, physical activity, and eating behaviors from 0 to 6 or 12 mo (outcomes, Y). Methods: In a trial of integrated behavior therapy, adults with obesity and depression were randomized to intervention (n=59) or usual care (n=49). The yearlong intervention included 6 in-person problem solving therapy (PST) sessions for depression by 2 mo, 3 additional PST sessions for depression and 11 home videos on lifestyle changes for weight loss by 6 mo, and 6 maintenance calls by 12 mo. Participants completed validated conscious and nonconscious facial emotion viewing tasks in fMRI at 0 and 2 mo (time point corresponding to initial PST for depression in the intervention) and weight and height (baseline only) measurements, 7-day physical activity recalls, and 24-hour dietary recalls at 0, 6, and 12 mo. Analyses tested mediation as showing both a significant treatment effect (X) of the intervention vs. usual care on the mediator (X->M, path a ) and a significant correlation of the mediator with the outcome either as a main effect or an interaction effect by treatment group (M->Y, path b ). Results: Compared with usual care, the intervention led to significantly reduced nonconscious reactivity to threat-related facial emotions (fear, anger) at 2 mo for the left (-0.89, 95% CI -1.64 to -0.14; P =.02) and right amygdala (-0.84, 95% CI -1.54 to -0.13; P =.02) ( path a ). These reductions correlated significantly with increased leisure-time physical activity (MET minutes/wk) at 12 mo: main effect -686.0 (95% CI -1127.9 to -244.1; P =.003) and interaction effect 664.7 (95% CI 73.1 to 1256.4; P =.03) for the left amygdala and main effect -692.9 (95% CI -1365.3 to -20.6; P= .04) for the right amygdala. Similarly, the reductions correlated significantly with increased energy expenditure (kcal/kg/d) at 12 mo: main effect -1.72 (95% CI -2.49 to -0.95; P P P =.006) and interaction effect 1.94 (95% CI 0.50 to 3.38; P =.01) for the right amygdala ( path b ). Nonconscious reactivity to threat in bilateral amygdala did not correlate significantly with changes in BMI or eating behaviors. Conclusions: Reduced nonconscious reactivity to threat in bilateral amygdala in response to initial PST for depression significantly mediated improvements in leisure-time physical activity and energy expenditure. Results advance the understanding of neural mechanisms underlying behavior therapy in obesity and inform intervention optimization to enhance efficacy.

Objective: To identify distinct profiles of obese depressed patients in an ongoing trial that tests the effectiveness and implementation potential of an integrated care model in primary care combining standard behavioral weight loss treatment and problem solving therapy plus as-needed antidepressant(s). Design and Methods: Analysis of variance for continuous and Chi-square tests for categorical variables compared 4 domains (sociodemographic, behavioral, clinical and psychosocial characteristics) among 4 severity categories of obese depressed participants (i.e., body mass index [BMI]2 and Depression Symptom Checklist 20 [SCL20] Results: Participants (n=322) had baseline mean (SD) age of 50.4 (12.2) years, BMI of 36.7 (6.4) kg/m 2 , and SCL20 of 1.5 (0.5). Pairwise comparisons showed participants in the 4 categories had similar sociodemographic characteristics, but they differed significantly in the other 3 domains (Table). Discriminant analysis showed the combination of higher abdominal obesity, problems with usual activities (eg, work and family or leisure activities), higher anxiety, poorer self-reported mental health, and more obesity-related problems differentiated the highest from lowest severity category. The combination of lower abdominal obesity, more obese-related problems, and higher anxiety differentiated the 2 intermediate (lower obesity/high depression vs. high obesity/lower depression) categories. Conclusions: Discernable behavioral, clinical and psychosocial profiles reveal important variability according to comorbidity severity within a largely sociodemographically similar group of obese depressed adults. This insight may inform future analysis of heterogeneity of treatment effects and targeting of strategies to baseline participant profiles in a multicomponent intervention.