Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial.

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges' g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results - 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93-7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers - i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, ß-thromboglobulin, and platelet factor 4 (Hedges' gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention - which harnessed technology to maximize access and minimize resources - produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches. Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.

Associations of somatic depressive symptoms with body mass index, systemic inflammation, and insulin resistance in primary care patients with depression.

The somatic depressive symptom cluster (including appetite and sleep disturbances) is more strongly associated with insulin resistance (a diabetes risk marker) than other depressive symptom clusters. Utilizing baseline data from 129 primary care patients with depression but no diabetes in the eIMPACT trial (Mage = 59 years, 78% female, 50% Black), we examined associations of somatic depressive symptoms with insulin resistance (HOMA-IR), body mass index (BMI), and high-sensitivity C-reactive protein (hsCRP). We tested BMI and hsCRP as mediators and race as a moderator of these relationships. Hyperphagia was positively associated HOMA-IR (ß = 0.19, p = .048) and BMI (ß = 0.30, p < .001); poor appetite was negatively associated with HOMA-IR (ß = -0.24, p = .02); hypersomnia was positively associated with HOMA-IR (ß = 0.28, p = .003), BMI (ß = 0.26, p = .003), and hsCRP (ß = 0.23, p = .01); and disturbed sleep was positively associated with hsCRP (ß = 0.21, p = .04). BMI partially mediated hyperphagia and hypersomnia's associations with HOMA-IR; hsCRP partially mediated the hypersomnia-HOMA-IR association; and race moderated the hyperphagia-HOMA-IR association (positive for White participants but null for Black participants). People with depression experiencing hyperphagia and/or hypersomnia may be a subgroup with greater insulin resistance; BMI and hsCRP are likely pathways in these relationships. This study highlights the importance of considering the direction of somatic depressive symptoms in the context of cardiometabolic disease risk.

Associations of somatic depressive symptoms with food attentional bias and eating behaviors.

Recent evidence suggests that atypical major depressive disorder (MDD) - whose key features include the reversed somatic symptoms of hyperphagia (increased appetite) and hypersomnia (increased sleep) - is a stronger predictor of future obesity than other MDD subtypes. The mechanisms underlying this relationship are unclear. The present study sought to elucidate whether the individual symptoms of hyperphagia, hypersomnia, poor appetite, and disturbed sleep have differential relationships with food attentional bias, emotional eating, external eating, and restrained eating. This cross-sectional laboratory study involved 103 young adults without obesity (mean age = 20 years, 79% female, 26% non-White, mean BMI = 23.4 kg/m2). We measured total depressive symptom severity and individual symptoms of hyperphagia, poor appetite, and disturbed sleep using the Hopkins Symptom Checklist-20 (SCL-20) and added an item to assess hypersomnia; food attentional bias using a Food Stroop task; and self-reported eating behaviors using the Dutch Eating Behavior Questionnaire. Hyperphagia was positively associated with emotional eating but negatively associated with food attentional bias. Hypersomnia was negatively associated with emotional eating. Poor appetite was negatively associated with emotional eating. Disturbed sleep was positively associated with food attentional bias and emotional eating. An aggregate of the remaining 15 depressive symptoms (SCL-15) was positively associated with emotional and restrained eating. Our findings highlight the importance of examining the direction of somatic depressive symptoms, and they set the stage for future research to identify subgroups of people with depression at greatest risk for obesity (e.g., those with hyperphagia and/or disturbed sleep) and the mechanisms responsible for this elevated risk (e.g., emotional eating).

Depressive disorder subtypes, depressive symptom clusters, and risk of obesity and diabetes: A systematic review.

BACKGROUND: Overlapping but divided literatures suggest certain depression facets may pose greater obesity and diabetes risk than others. Our objectives were to integrate the major depressive disorder (MDD) subtype and depressive symptom cluster literatures and to clarify which facets are associated with the greatest cardiometabolic disease risk. METHODS: We conducted a systematic review of published studies examining associations of ≥2 MDD subtypes or symptom clusters with obesity or diabetes risk outcomes. We report which facets the literature is "in favor" of (i.e., having the strongest or most consistent results). RESULTS: Forty-five articles were included. Of the MDD subtype-obesity risk studies, 14 were in favor of atypical MDD, and 8 showed similar or null associations across subtypes. Of the symptom cluster-obesity risk studies, 5 were in favor of the somatic cluster, 1 was in favor of other clusters, and 5 were similar or null. Of the MDD subtype-diabetes risk studies, 7 were in favor of atypical MDD, 3 were in favor of other subtypes, and 5 were similar or null. Of the symptom cluster-diabetes risk studies, 7 were in favor of the somatic cluster, and 5 were similar or null. LIMITATIONS: Limitations in study design, sample selection, variable measurement, and analytic approach in these literatures apply to this review. CONCLUSIONS: Atypical MDD and the somatic cluster are most consistently associated with obesity and diabetes risk. Future research is needed to establish directionality and causality. Identifying the depression facets conferring the greatest risk could improve cardiometabolic disease risk stratification and prevention programs.

Effect of modernized collaborative care for depression on brain-derived neurotrophic factor (BDNF) and depressive symptom clusters: Data from the eIMPACT trial.

Brain-derived neurotrophic factor (BDNF) levels are lower in people with depression and are normalized following pharmacological treatment. However, it is unknown if psychological treatments for depression improve BDNF and if change in BDNF is a mediator of intervention effects on depressive symptoms. Therefore, using data from the eIMPACT trial, we sought to determine the effect of modernized collaborative care for depression on 12-month changes in BDNF and cognitive/affective and somatic depressive symptom clusters and to examine whether BDNF changes mediate intervention effects on depressive symptoms. 216 primary care patients with depression from a safety net healthcare system were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. Plasma BDNF was measured with commercially available kits, and depressive symptom clusters were assessed by the Patient Health Questionnaire-9. The intervention did not influence BDNF but did improve both the cognitive/affective and somatic clusters over 12 months. Changes in BDNF did not mediate the intervention effect on either cluster. Our findings suggest that modernized collaborative care is an effective treatment for both the cognitive/affective and somatic symptoms of depression and that the mechanism of action is not improvements in BDNF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02458690.

Associations between affective factors and high-frequency heart rate variability in primary care patients with depression.

OBJECTIVE: Depression is a risk factor for cardiovascular disease (CVD), and subgroups of people with depression may be at particularly elevated CVD risk. Lower high-frequency heart rate variability (HF HRV), which reflects diminished parasympathetic activation, is a candidate mechanism underlying the depression-CVD relationship and predicts cardiovascular events. Few studies have examined whether certain depression subgroups - such as those with co-occurring affective factors - exhibit lower HF HRV. The present study sought to assess associations between co-occurring affective factors and HF HRV in people with depression. METHODS: Utilizing baseline data from the 216 primary care patients with depression in the eIMPACT trial, we examined cross-sectional associations of depression's co-occurring affective factors (i.e., anxiety symptoms, hostility/anger, and trait positive affect) with HF HRV. HF HRV estimates were derived by spectral analysis from electrocardiographic data obtained during a supine rest period. RESULTS: Individual regression models adjusted for demographics and depressive symptoms revealed that anxiety symptoms (standardized regression coefficient ß = -0.24, p = .002) were negatively associated with HF HRV; however, hostility/anger (ß = 0.02, p = .78) and trait positive affect (ß = -0.05, p = .49) were not. In a model further adjusted for hypercholesterolemia, hypertension, diabetes, body mass index, current smoking, CVD prevention medication use, and antidepressant medication use, anxiety symptoms remained negatively associated with HF HRV (ß = -0.19, p = .02). CONCLUSION: Our findings suggest that, in adults with depression, those with comorbid anxiety symptoms have lower HF HRV than those without. Co-occurring anxiety may indicate a depression subgroup at elevated CVD risk on account of diminished parasympathetic activation.

Negative urgency and central adiposity in a community sample: Moderated mediation by depressive symptoms and eating behaviors.

Negative urgency - acting rashly in response to negative emotions - is a risk factor for central adiposity. We examine whether the relationship between negative urgency and waist-to-height ratio (WHtR) is mediated by eating behaviors (emotional eating, external eating, and cognitive restraint) and moderated by depressive symptom severity, factors that could be targeted to reduce risk associated with negative urgency. Using baseline data from the Nathan Kline Institute-Rockland Sample (N = 872; mean age = 42.4 years, SD = 15.3; 65% female; 27% non-White; mean body mass index = 27.9 kg/m2, SD = 5.9), we conducted a series of mediation and moderated mediation analyses controlling for age, sex, race, and socioeconomic status. Overall, there was a positive association between negative urgency and WHtR. Emotional eating (ab = 0.02, SE = 0.003, 95% CI [0.02, 0.03]) and uncontrolled eating (ab = 0.008, SE = 0.002, 95% CI [0.004, 0.01]) were partial mediators of the relationship between negative urgency and WHtR, while cognitive restraint was not. In a parallel mediation model, emotional eating remained significant, while uncontrolled eating did not. Depressive symptom severity moderated the indirect effect of negative urgency on WHtR through emotional eating (bint = -0.08, p < .001) but not the direct effect of negative urgency on WHtR. Our results indicate that emotional eating is a viable potential mechanism explaining the relationship between negative urgency and WHtR, and the indirect effect of negative urgency on WHtR through emotional eating becomes stronger as depressive symptom severity decreases.

Depressive symptom severity as a predictor of attendance in the HOME behavioral weight loss trial.

OBJECTIVE: We examined whether total depressive symptoms and symptom clusters predicted behavioral weight loss attendance among economically disadvantaged adults in a randomized controlled trial. METHODS: 150 adults with obesity were randomized to 12 months of in-person, video conference, or enhanced usual care weight loss groups. We categorized percent session attendance in the intervention arms into three levels: no attendance, poorer attendance, and better attendance. RESULTS: Higher baseline Patient Health Questionnaire-8 (PHQ-8) score was associated with a greater odds of being in the poorer versus better attendance group (OR = 1.94, 95% CI: 1.02-3.69, p = .04). A similar relationship between PHQ-8 score and odds of being in the no attendance versus better attendance group was observed but was not statistically significant (OR = 1.63, 95% CI: 0.94-2.81, p = .08). Both cognitive/affective and somatic clusters contributed to the depressive symptoms-attendance relationships. CONCLUSION: Greater depressive symptoms at the start of a behavioral weight loss program may predict poorer subsequent session attendance. Screening for and addressing depression may improve intervention uptake. ClinicalTrials.gov Identifier: NCT02057952.