Social Induction via a Social Behavioral Intervention on Changes in Metabolic Risk Factors: A Randomized Controlled Trial in Rural Appalachia, United States.

OBJECTIVE: To conduct a randomized controlled trial examining the effects of a social network intervention on health. PARTICIPANTS AND METHODS: The Microclinic Social Network Program randomized controlled trial (implemented from June 1, 2011, through December 31, 2014) delivered weekly social-health classroom interventions for 9 to 10 months vs standard of care. Longitudinal multilevel analyses examined end-of-trial and 6-month post-intervention outcomes. Social network effects were estimated via a novel social induction ratio. RESULTS: We randomized 494 participants, comprising 27 classroom clusters from five neighborhood cohorts. Compared with controls, the intervention showed decreased body weight -6.32 pounds (95% CI, -8.65 to -3.98; overall P<.001), waist circumference -1.21 inches (95% CI, -1.84 to -0.58; overall P<.001), hemoglobin A1c % change -1.60 (95% CI, -1.88 to -1.33; overall P<.001), mean arterial blood pressure -1.83 mm Hg (95% CI, -3.79 to 0.32; overall P<.01), borderline-increased high-density lipoprotein cholesterol 1.09 (95% CI, 0.01-2.17; P=.05; overall P=.01). At 6 months post-intervention, net improvements were: weight change 97% sustained (P<.001), waist circumference change 92% sustained (P<.001), hemoglobin A1c change 82.5% sustained (P<.001), high-density lipoprotein change 79% sustained (overall P=.01), and mean arterial blood pressure change greater than 100% sustained improvement of -4.21 mm Hg (P<.001). Mediation analysis found that diet and exercise did not substantially explain improvements. In the intent-to-treat analysis of social causal induction, the weight-change social induction ratio (SIR) was 1.80 for social-network weight change-meaning that social networks explained the greater weight loss in the intervention than controls. Furthermore, we observed an even stronger weight-loss SIR of 2.83 at 6 months post-intervention. CONCLUSION: Results show intervention effectiveness for improving health in resource-limited communities, with SIR demonstrating that social-network effects helped induce such improvements. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01651065.

Social network enhanced behavioral interventions for diabetes and obesity: A 3 arm randomized trial with 2 years follow-up in Jordan.

While obesity and diabetes are rising pandemics, few low-cost and effective prevention and management strategies exist, especially in the Middle East. Nearly 20% of adults in Jordan suffer from diabetes, and over 75% are overweight or obese. Social network-based programs have shown promise as a viable public health intervention strategy to address these growing crises. We evaluated the effectiveness of the Microclinic Program (MCP) via a 6-month multi-community randomized trial in Jordan, with follow-up at 2 years. The MCP leverages existing social relationships to propagate positive health behaviors and information. We recruited participants from 3 community health centers in Amman, Jordan. Participants were eligible for the study if they had diabetes, pre-diabetes, or possessed ≥1 metabolic risk factor along with a family history of diabetes. We randomized participants into three trial arms: (A Group) received the Full MCP with curriculum-activated social network interactions; (B Group) received Basic MCP educational sessions with organic social network interactions; or (C Group-Control) received standard care coupled with active monitoring and parallel screenings. Groups of individuals were randomized as units in a 3:1:1 ratio, with resulting group sizes of n = 540, 186, and 188 in arms A, B, and C, respectively. We assessed the overall changes in body weight, fasting glucose, hemoglobin A1c (HbA1c) and mean arterial blood pressure between study arms in multiple evaluations across 2 years (including at 6-months and 2-years follow-up). We investigated the effectiveness of Full and Basic MCP social network interventions using multilevel models for longitudinal data with hierarchical nesting of individuals within MCP classrooms, within community centers, and within temporal cohorts. We observed significant overall 2-year differences between all 3 groups for changes in body weight (P = 0.0003), fasting blood glucose (P = 0.0015), and HbA1c (P = 0.0004), but not in mean arterial blood pressure (P = 0.45). However, significant changes in mean arterial pressure were observed for Full MCP versus controls (P = 0.002). Weight loss in the Full MCP exceeded (-0.97 kg (P<0.001)) the Basic MCP during the intervention. Furthermore, both Full and Basic MCP yielded greater weight loss compared to the control group at 2 years. The Full MCP also sustained a superior fasting glucose change over 2 years (overall P<0.0001) versus the control group. For HbA1c, the Full MCP similarly led to greater 6-month reduction in HbA1c versus the control group (P<0.001), with attenuation at 2 years. For mean arterial blood pressure, the Full MCP yielded a greater drop in blood pressure versus control at 6 months; with attenuation at 2 years. These results suggest that activated social networks of classroom interactions can be harnessed to improve health behaviors related to obesity and diabetes. Future studies should investigate how public health policies and initiatives can further leverage social network programs for greater community propagation. Trial registration. ClinicalTrials.gov Identifier: NCT01818674.

Proteomic profiles of cytokines and chemokines in moderate to severe depression: Implications for comorbidities and biomarker discovery.

Objective: This study assessed the proteomic profiles of cytokines and chemokines in individuals with moderate to severe depression, with or without comorbid medical disorders, compared to healthy controls. Two proteomic multiplex platforms were employed for this purpose. Metods: An immunofluorescent multiplex platform and an aptamer-based method were used to evaluate 32 protein analytes from 153 individuals with moderate to severe major depressive disorder (MDD) and healthy controls (HCs). The study focused on determining the level of agreement between the two platforms and evaluating the ability of individual analytes and principal components (PCs) to differentiate between the MDD and HC groups. Additionally, the study investigated the relationship between PCs consisting of chemokines and cytokines and comorbid inflammatory and cardiometabolic diseases. Findings: Analysis revealed a small or moderate correlation between 47% of the analytes measured by the two platforms. Two proteomic profiles were identified that differentiated individuals with moderate to severe MDD from HCs. High eotaxin, age, BMI, IP-10, or IL-10 characterized profile 1. This profile was associated with several cardiometabolic risk factors, including hypertension, hyperlipidemia, and type 2 diabetes. Profile 2 is characterized by higher age, BMI, interleukins, and a strong negative loading for eotaxin. This profile was associated with inflammation but not cardiometabolic risk factors. Conclusion: This study provides further evidence that proteomic profiles can be used to identify potential biomarkers and pathways associated with MDD and comorbidities. Our findings suggest that MDD is associated with distinct profiles of proteins that are also associated with cardiometabolic risk factors, inflammation, and obesity. In particular, the chemokines eotaxin and IP-10 appear to play a role in the relationship between MDD and cardiometabolic risk factors. These findings suggest that a focus on the interplay between MDD and comorbidities may be useful in identifying potential targets for intervention and improving overall health outcomes.

Correction: Ramadan fasting and weight change trajectories: Time-varying association of weight during and after Ramadan in low-income and refugee populations.

[This corrects the article DOI: 10.1371/journal.pgph.0000371.].

Insulin resistance and accelerated cognitive aging.

Insulin resistance may be an early sign of metabolic dysfunction with the potential to lead to neuropsychiatric sequelae in the long term. In order to identify whether insulin resistance in otherwise healthy young and middle-aged adults is associated with preclinical signs of neuropsychiatric impairment, we recruited 126 overweight but nondiabetic, nondepressed individuals who completed an insulin suppression test for direct measurement of insulin resistance as well as a battery of cognitive and neuropsychiatric measures. Insulin resistance was associated with weaker performance on a fine motor task (Purdue Pegboard) as well as increases in subclinical symptoms of depression. We submit that insulin resistance in early to mid-adulthood may be an important predictor of long-term risk for metabolic, psychiatric, and neurobehavioral dysfunction.

Maternal attachment insecurity, maltreatment history, and depressive symptoms are associated with broad DNA methylation signatures in infants.

The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was obtained from 32 of their infants for a large-scale analysis of methylation patterns across 5 × 106 individual CpG dinucleotides, using clustering-based significance criteria to control for multiple comparisons. We found that tens of thousands of individual infant CpGs were alternatively methylated in association with maternal attachment insecurity, maltreatment in childhood, and antenatal and postpartum depressive symptoms, including genes implicated in developmental patterning, cell-cell communication, hormonal regulation, immune function/inflammatory response, and neurotransmission. Density of DNA methylation at selected genes from the result set was also significantly associated with toddler socioemotional and behavioral problems. This is the first report to identify novel regions of the human infant genome at which DNA methylation patterns are associated longitudinally both with maternal characteristics and with offspring socioemotional and behavioral problems in toddlerhood.

Human Papillomavirus Vaccination Over Time in Heterosexual and Sexual Minority Adults in the United States.

Purpose: We proposed to identify the factors that determine the trends in human papillomavirus (HPV) vaccination initiation and completion among heterosexual and sexual minority adults. Methods: Using National Health and Nutrition Examination Survey database from 2007 to 2016, we performed chi-squared tests and multivariate logistic regression analysis. Results: Heterosexual females initiated vaccination at 23.5% compared with sexual minority females at 34.6% (p<0.001). Although heterosexual males also had a lower vaccination initiation than sexual minority males (7.7% vs. 15.5%; p=0.12), their completion rate appeared higher (38% vs. 17%; p=0.14). Conclusion: Interventions are needed to enhance support for completion rates of HPV vaccine among sexual minority individuals.

Ramadan fasting and weight change trajectories: Time-varying association of weight during and after Ramadan in low-income and refugee populations.

Obesity is a significant driver of the global burden of non-communicable diseases. Fasting is one approach that has been shown to improve health outcomes. However, the effects of Ramadan fasting differ in that the type, frequency, quantity, and time of food consumption vary. This phenomenon requires in-depth evaluation considering that 90% of Muslims (~2 billion people) fast during Ramadan. To address this issue, we evaluated the pattern of weight change during and following Ramadan for a total of 52 weeks. The study was conducted in Amman, Jordan. Between 2012 and 2015, 913 participants were recruited as part of a trial investigating the efficacy of a weight loss intervention among those with or at risk for diabetes. Weight was measured weekly starting at the beginning of Ramadan, and changes were analyzed using discrete and spline models adjusted for age, sex, and trial group. Results show slight weight gain within the first two weeks and weight loss in the subsequent weeks. During the first week of Ramadan, the estimate for a weight increase was 0·427 kg, (95% CI: -0·007, 0·861) relative to baseline, compared to an estimated weight reduction of 0·55kg (95% CI: 0·05, 1·05) by the 8th week relative to baseline. There was clear evidence of gradual weight gain from week 8 until week 26 with an estimated weight gain of 2.547 kg (95% CI: 1.567, 3.527) at week 26 relative to baseline. A sharp drop of 2.66kg in weight was observed between the 26th and 28th week before it stabilized. Our results show that weight changes occurred during and after Ramadan. Weight fluctuations may affect health risks, and thus, findings from this study can inform interventions. Public health agencies could leverage this period of dietary change to sustain some of the benefits of fasting. The authors (DEZ, EFD) acknowledge the Mulago Foundation, the Horace W. Goldsmith Foundation, Robert Wood Johnson Foundation, and the World Diabetes Foundation. TRIAL REGISTRATION. Clinicaltrials.gov registry identifier: NCT01596244.

Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study.

OBJECTIVE: Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression. There is accumulating biological evidence linking insulin resistance, another highly prevalent condition, and depressive disorders. The objectives of this study were to examine whether three surrogate measures of insulin resistance (high triglyceride-HDL [high-density lipoprotein] ratio; prediabetes, as indicated by fasting plasma glucose level; and high central adiposity, as measured by waist circumference) at the time of study enrollment were associated with an increased rate of incident major depressive disorder over a 9-year follow-up period and to assess whether the new onset of these surrogate measures during the first 2 years after study enrollment was predictive of incident major depressive disorder during the subsequent follow-up period. METHODS: The Netherlands Study of Depression and Anxiety (NESDA) is a multisite longitudinal study of the course and consequences of depressive and anxiety disorders in adults. The study population comprised 601 NESDA participants (18-65 years old) without a lifetime history of depression or anxiety disorders. The study's outcome was incident major depressive disorder, defined using DSM-IV criteria. Exposure measures included triglyceride-HDL ratio, fasting plasma glucose level, and waist circumference. RESULTS: Fourteen percent of the sample developed major depressive disorder during follow-up. Cox proportional hazards models indicated that higher triglyceride-HDL ratio was positively associated with an increased risk for incident major depression (hazard ratio=1.89, 95% CI=1.15, 3.11), as were higher fasting plasma glucose levels (hazard ratio=1.37, 95% CI=1.05, 1.77) and higher waist circumference (hazard ratio=1.11 95% CI=1.01, 1.21). The development of prediabetes in the 2-year period after study enrollment was positively associated with incident major depressive disorder (hazard ratio=2.66, 95% CI=1.13, 6.27). The development of high triglyceride-HDL ratio and high central adiposity (cut-point ≥100 cm) in the same period was not associated with incident major depression. CONCLUSIONS: Three surrogate measures of insulin resistance positively predicted incident major depressive disorder in a 9-year follow-up period among adults with no history of depression or anxiety disorder. In addition, the development of prediabetes between enrollment and the 2-year study visit was positively associated with incident major depressive disorder. These findings may have utility for evaluating the risk for the development of major depression among patients with insulin resistance or metabolic pathology.

Association of Rapid Eye Movement Sleep With Mortality in Middle-aged and Older Adults.

Importance: Rapid eye movement (REM) sleep has been linked with health outcomes, but little is known about the relationship between REM sleep and mortality. Objective: To investigate whether REM sleep is associated with greater risk of mortality in 2 independent cohorts and to explore whether another sleep stage could be driving the findings. Design, Setting, and Participants: This multicenter population-based cross-sectional study used data from the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and Wisconsin Sleep Cohort (WSC). MrOS participants were recruited from December 2003 to March 2005, and WSC began in 1988. MrOS and WSC participants who had REM sleep and mortality data were included. Analysis began May 2018 and ended December 2019. Main Outcomes and Measures: All-cause and cause-specific mortality confirmed with death certificates. Results: The MrOS cohort included 2675 individuals (2675 men [100%]; mean [SD] age, 76.3 [5.5] years) and was followed up for a median (interquartile range) of 12.1 (7.8-13.2) years. The WSC cohort included 1386 individuals (753 men [54.3%]; mean [SD] age, 51.5 [8.5] years) and was followed up for a median (interquartile range) of 20.8 (17.9-22.4) years. MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (percentage REM sleep SD = 6.6%) after adjusting for multiple demographic, sleep, and health covariates (age-adjusted hazard ratio, 1.12; fully adjusted hazard ratio, 1.13; 95% CI, 1.08-1.19). Results were similar for cardiovascular and other causes of death. Possible threshold effects were seen on the Kaplan-Meier curves, particularly for cancer; individuals with less than 15% REM sleep had a higher mortality rate compared with individuals with 15% or more for each mortality outcome with odds ratios ranging from 1.20 to 1.35. Findings were replicated in the WSC cohort despite younger age, inclusion of women, and longer follow-up (hazard ratio, 1.17; 95% CI, 1.03-1.34). A random forest model identified REM sleep as the most important sleep stage associated with survival. Conclusions and Relevance: Decreased percentage REM sleep was associated with greater risk of all-cause, cardiovascular, and other noncancer-related mortality in 2 independent cohorts.

A social-network behavioral health program on sustained long-term body weight and glycemic outcomes: 2-year follow-up of a 4-month Microclinic Health Program in Jordan.

The burden of chronic diseases like diabetes and obesity is rapidly increasing in low and lower-middle income countries. This work assesses the long-term efficacy of a social-network based community health program for the management and prevention of type 2 diabetes. METHODS: The 4-month Microclinic Social Network Behavioral Health Program in Jordan (J-MCP) was an intervention for obesity and diabetes prevention and management conducted in the Kingdom of Jordan. Weight and HbA1c were collected at baseline, end of the 4-month program, and then 12 and 24 months after baseline. Multi-level longitudinal repeated measures analysis estimated the long-term change in metabolic outcomes, and estimated the intra-class correlations (ICCs) for assessing the degree of clustering that different social network levels, of microclinic group vs. classroom group vs. clinic geographic location vs. cohort temporal wave, contributed to body weight and glycemic changes. RESULTS: Of 315 participants, 83.2% completed the J-MCP program, with 90% followup at 12-months, and 70% at 24-months. At the end of the 4-month program, participants experienced a -2.8 kg (95% CI: -3.6 to -2.1) mean body weight decrease, a corresponding -1.1 kg/m2 (-1.3 to -0.8) BMI decrease, and a -0.5% reduction in HbA1c (-0.6 to -0.3). At year 1, we observed significant mean weight reduction of -1.8 kg (-2.7 to -0.9), a corresponding -0.7 kg/m2 (-1.0 to -0.4) reduction in BMI, as well as a -0.4% (-0.6 to -0.3) sustained reduction in HbA1c. At 2 years, participants sustained mean weight loss of -1.6 kg (-2.6 to -0.5), a -0.42 kg/m2 (-0.8 to -0.04) reduction in BMI, and an absolute -1.0% (-1.1 to -0.8) sustained reduction in HbA1c. Analyzing different social network levels, classroom group explained ~50% of total clustering of total weight loss and 22% of HbA1c trajectories during the short 4 month intervention. However, during 12 and 24 month followup, microclinic social group clustering explained ~75% to 92% of long-term weight loss trajectories, and 55% of long-term HbA1c trajectories. The pattern of 1-2 year sustainability of the weight and HbA1c decreases was largely attributed to the microclinic social network clusters. CONCLUSION: Results demonstrate that the 4-month J-MCP behavioral intervention yielded important 2-year sustained weight and HbA1c reductions, which were mostly attributed to microclinic social groups.

Neural correlates of liraglutide effects in persons at risk for Alzheimer's disease.

Insulin resistance (IR) is a metabolic state preceding development of type 2 diabetes (DM2), cardiovascular disease, and neurodegenerative disorders, including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP) agonist, is an insulin-sensitizing agent with neuroprotective properties, as shown in animal studies. The purpose of this double-blinded, placebo-controlled study was to examine the neural effects of administration of liraglutide in cognitively normal late middle-aged individuals with subjective cognitive complaints (half of subjects had family history of AD). Seed-based resting state connectivity using functional magnetic resonance imaging (fMRI) was conducted before and after 12 weeks of liraglutide treatment or placebo. Neuropsychological testing was conducted before and after treatment to determine whether there were any potential behavioral correlates to neural changes. RESULTS: At baseline (time point 1), higher fasting plasma glucose (FPG) was associated with decreased connectivity between bilateral hippocampal and anterior medial frontal structures. At time point 2, we observed significant improvement in intrinsic connectivity within the default mode network (DMN) in the active group relative to placebo. There were no detectable cognitive differences between study groups after this duration of treatment. To our knowledge, this is the first placebo-controlled study to report neural effects of liraglutide in a middle-aged population with subjective cognitive complaints. Larger and longer duration studies are warranted to determine whether liraglutide has neuroprotective benefits in individuals at risk for AD.

Neural and Endocrine Correlates of Early Life Abuse in Youth With Depression and Obesity.

Depression and insulin resistance are becoming increasingly prevalent in younger populations. The origin and consequence of insulin resistance in depressed youth may, in part, be rooted in exposure to environmental stressors, such as early life abuse, that may lead to aberrant brain motivational networks mediating maladaptive food-seeking behaviors and insipient insulin resistance. In this paper, we aimed to investigate the impact of early life abuse on the development of insulin resistance in depressed and overweight youth aged 9 to 17 years. We hypothesized that youth with the greatest burden of early life abuse would have the highest levels of insulin resistance and corresponding aberrant reward network connectivities. To test this hypothesis, we evaluated sixty-nine depressed and overweight youth aged 9 to 17, using multimodal assessments of early life abuse, food-seeking behavior, and insulin resistance. Based on results of the Childhood Trauma Questionnaire (CTQ), we separated our study participants into two groups: 35 youth who reported high levels of the sum of emotional, physical, or sexual abuse and 34 youth who reported insignificant or no levels of any abuse. Results of an oral glucose tolerance test (OGTT) and resting state functional connectivity (RSFC), using the amygdala, insula, and nucleus accumbens (NAcc) as seed-based reward network regions of interest, were analyzed for group differences between high abuse and low abuse groups. High abuse youth exhibited differences from low abuse youth in amygdala-precuneus, NAcc-paracingulate gyrus, and NAcc-prefrontal cortex connectivities, that correlated with levels of abuse experienced. The more different their connectivity from of that of low abuse youth, the higher were their fasting glucose and glucose at OGTT endpoint. Importantly, level of abuse moderated the relation between reward network connectivity and OGTT glucose response. In contrast, low abuse youth showed hyperinsulinemia and more insulin resistance than high abuse youth, and their higher OGTT insulin areas under the curve correlated with more negative insula-precuneus connectivity. Our findings suggest distinct neural and endocrine profiles of youth with depression and obesity based on their histories of early life abuse.