The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production.

Depression has been associated with reduced bone mass in adults, but the mechanisms remain unclear. In addition, little is known about the association between depression and bone health during growth and development. To address this knowledge gap, we examined bone density and structure in 222 adolescents and young adults (69% females, mean±SD age: 19.0±1.5 years), enrolled within one month of starting a selective serotonin reuptake inhibitor (SSRI) or unmedicated. Psychiatric functioning was assessed with self-report and researcher-administered instruments, including the Longitudinal Interval Follow-up Evaluation for Adolescents (A-LIFE). Anthropometric and laboratory measures included dual-energy x-ray absorptiometry and peripheral quantitative computed tomography scans. Linear multivariable regression analysis tested the association between depression and bone mass, after accounting for relevant confounders. The presence of current depression was associated with a significant reduction in age-sex-height-race-specific bone mineral density (BMD) and content (BMC) of total body less head and lumbar spine. The findings varied by assessment method with self-report scales, capturing symptom severity over the prior week or two, yielding the weakest associations. Depression was also associated with reduced cortical thickness and a trend for increased endosteal circumference. In contrast, generalized anxiety disorder was not associated with bone deficits. In sum, depressive illness is associated with significantly lower bone mass in youths. Future investigations must examine whether bone recovery is possible following depression remission or whether remedial interventions are warranted to optimize bone mass in order to minimize the long-term risk of osteoporosis.

BackgroundFirearm injuries disproportionately affect young, male, non-White populations, causing substantial individual and societal burden. Annual costs for hospitalized firearm injuries have not been widely described, as most previous cost studies have focused on lifetime costs. We examined a nationally-representative database of hospitalizations in the US to estimate per-hospital and overall hospital costs for firearm injuries by intent, type of weapon, and payer source.MethodsWe conducted a retrospective cohort study of all firearm injury hospitalizations in the National Inpatient Sample from 2003 through 2013. The National Inpatient Sample, maintained by the Healthcare Utilization Project, is a stratified and weighted national sample of more than 20% of all hospitals. All admissions for firearm injuries were identified through Ecodes, yielding a weighted total of 336,785 for the study period. Average annual per-patient and overall hospital costs were estimated using generalized linear modelling, controlling for patient and hospital variables. Costs by intent, firearm type, and payer sources were estimated.ResultsAnnually from 2003 through 2013, 30,617 hospital admissions were for firearm injuries, for an annual rate of 10.1 admissions per 100,000 US population. More than 80% of hospitalizations were among individuals aged 15–44, and rates were nine times higher for males than females and nearly ten times higher for the Black than the White population. More than 60% of admissions were for assaults, and 70% of the injuries that had a known firearm type were from handguns. The average annual admission cost was $622 million. The highest per-admission costs were for injuries from assault weapons ($32,237 per admission) and for legal intervention ($33,462 per admission), but the highest total costs were for unspecific firearm type ($373 million) and assaults ($389 million). A quarter of firearm injury hospitalizations were among the uninsured, yielding average annual total costs of $155 million.ConclusionHospitals can project that government insurance will be the highest source for firearm injury reimbursement, and depending on healthcare access laws, that many of their firearm injury admissions will not be covered by insurance.

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Objective Substantial evidence exists to indicate bidirectional relationships between obesity and depressive disorders and the importance of fat distribution to this relationship. This analysis used a well-characterized sample of individuals in late adolescence to determine the association between depressive illness and fat distribution. Method Medically healthy, 15 to 20 year-olds, one-half of whom had recently begun treatment with a selective serotonin reuptake inhibitor underwent a comprehensive psychiatric evaluation that resulted in diagnostic classification and weekly psychiatric disorder ratings over the prior 4 months, using the Longitudinal Interval Follow-up Evaluation. A whole body scan, using dual x-ray absorptiometry, allowed estimatiions of total body less head (TBLH), total mass, fat mass, and visceral adipose tissue mass (VAT). Assessments occurred between September 2010 and April 2014. linear regression analyses, adjusted for relevant covariates, examined the association between DSM-IV-TR major depressive disorder (MDD) and VAT. These procedures also determined whether significant associations were confined to overweight/obese participants. Results The analysis included data from 200 participants (71% females, mean age: 19.0±1.6 years), of whom 128 had current MDD. The presence of MDD was associated with increased fat mass among overweight/obese (Cohen’s d=0.79, p<0.002), but not normal weight, participants. This was true of both visceral and non-visceral fat mass measures. Accounting for the presence of generalized anxiety disorder did not alter the findings. Conclusion In adolescents, relationships between central adiposity and MDD may be confined to those who are overweight/obese. Despite the high co-morbidity of GAD and depressive disorders, only the latter appeared to be significantly associated with central adiposity.

Objective In prior work, we have identified a relationship between symptom burden and vascular outcomes in bipolar disorder. We sought to replicate these findings using a readily accessible measure of mood disorder chronicity and vascular mortality. Methods We conducted a mortality assessment using the National Death Index for 1,716 participants with bipolar I disorder from the National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium. We assessed the relationship between the duration of the most severe depressive and manic episodes and time to vascular mortality (cardiovascular or cerebrovascular) using Cox Proportional Hazards Models, adjusting for potentially confounding variables. Results Mortality was assessed a mean of 7 years following study intake at which time 58 participants died, 18 from vascular causes. These participants were depressed much longer than their counterparts (Wilcoxon Rank Sum Z=2.30, p=0.02) and the duration of the longest depressive episode in years was significantly associated with time to vascular mortality in models (HR=1.16, 95% C.I. 1.02–1.33, p=0.02), which controlled for age, gender, vascular disease equivalents, and vascular disease risk factors. The duration of longest mania was not related to vascular mortality. Conclusion The duration of the most severe depression is independently predictive of vascular mortality, lending further support to the idea that mood disorders hasten vascular mortality in a dose-dependent fashion. Further study of relevant mechanisms by which mood disorders may hasten vascular disease and of integrated treatments for mood and cardiovascular risk factors is warranted.

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Background Racial/ethnic disparity has been documented in a wide variety of health outcomes, and environmental components are contributors. For example, food deserts have been tied to obesity rates. Pedestrian injuries are strongly tied to environmental factors, yet no studies have examined racial disparity in pedestrian injury rates. We examine a nationally-representative sample of pedestrian-related hospitalizations in the United States to identify differences in incidence, severity, and cost by race/ethnicity. Methods Patients with ICD diagnosis E-codes for pedestrian injuries were drawn from the United States Nationwide Inpatient Sample (2009–2016). Rates were calculated using the United States Census. Descriptive statistics and generalized linear regression were used to examine characteristics (age, sex, severity of illness, mortality rates, hospital admissions, length of stay, total costs) associated with hospitalizations for pedestrian injuries. Results The annual average of pedestrian-related deaths exceeded 5000 per year and hospitalizations exceeded 47,000 admissions per year. The burden of injury from pedestrian-related hospitalizations was higher among Black, Hispanic, and Multiracial/Other groups in terms of admission rates, costs per capita, proportion of children injured, and length of stay compared to Whites and Asian or Pacific Islander race/ethnicities. Compared to Whites, hospital admission rates were 1.92 (95% CI: 1.89–1.94) and 1.20 (95% CI: 1.19–1.21) times higher for Multiracial/Other and Blacks, respectively. Costs per capita ($USD) were $6.30, $4.14, and $3.22 for Multiracial/Others, Blacks, and Hispanics, compared to $2.88 and $2.32 for Whites and Asian or Pacific Islanders. Proportion of lengths of stay exceeding one week were larger for Blacks (26.4%), Hispanics (22.6%), Asian or Pacific Islanders (23.1%), and Multiracial/Other (24.1%), compared to Whites (18.6%). Extreme and major loss of function proportions were also highest among Black (34.5%) and lowest among Whites (30.2%). Conclusions Results from this study show racial disparities in pedestrian injury hospitalization rates and outcomes, particularly among Black, Hispanic, and Multiracial/Other race/ethnicity groups and support population and system-level approaches to prevention. Access to transportation is an indicator for health disparity, and these results indicate that access to safe transportation also shows inequity by race/ethnicity.