The researcher's guide to selecting biomarkers in mental health studies.

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability.

Refinement of a Preliminary Case Definition for Use in Traumatic Brain Injury Surveillance.

OBJECTIVE: Current methods used to measure incidence of traumatic brain injury (TBI) underestimate its true public health burden. The use of self-report surveys may be an approach to improve these estimates. An important step in public health surveillance is to define a public health problem using a case definition. The purpose of this article is to outline the process that the Centers for Disease Control and Prevention undertook to refine a TBI case definition to be used in surveillance using a self-report survey. SETTING: Survey. PARTICIPANTS: A total of 10 030 adults participated via a random digit-dial telephone survey from September 2018 to September 2019. MAIN MEASURES: Respondents were asked whether they had sustained a hit to the head in the preceding 12 months and whether they experienced a series of 12 signs and symptoms as a result of this injury. DESIGN: Head injuries with 1 or more signs/symptoms reported were initially categorized into a 3-tiered TBI case definition (probable TBI, possible TBI, and delayed possible TBI), corresponding to the level of certainty that a TBI occurred. Placement in a tier was compared with a range of severity measures (whether medical evaluation was sought, time to symptom resolution, self-rated social and work functioning); case definition tiers were then modified in a stepwise fashion to maximize differences in severity between tiers. RESULTS: There were statistically significant differences in the severity measure between cases in the probable and possible TBI tiers but not between other tiers. Timing of symptom onset did not meaningfully differentiate between cases on severity measures; therefore, the delayed possible tier was eliminated, resulting in 2 tiers: probable and possible TBI. CONCLUSION: The 2-tiered TBI case definition that was derived from this analysis can be used in future surveillance efforts to differentiate cases by certainty and from noncases for the purpose of reporting TBI prevalence and incidence estimates. The refined case definition can help researchers increase the confidence they have in reporting survey respondents' self-reported TBIs as well as provide them with the flexibility to report an expansive (probable + possible TBI) or more conservative (probable TBI only) estimate of TBI prevalence.

Chronic Disease Indicators: 2022-2024 Refresh and Modernization of the Web Tool.

Easy access and display of state-level estimates of the prevalence of chronic diseases and their risk factors can guide evidence-based decision-making, policy development, and tailored efforts to improve population health outcomes; however, these estimates are often presented across multiple websites and reports. The Chronic Disease Indicators (CDI) web tool (www.cdc.gov/cdi) disseminates state-level data compiled from various data sources, including surveys, vital records, and administrative data, and applies standardized definitions to estimate and track a wide range of key indicators of chronic diseases and their risk factors. In 2022-2024, the indicators were refreshed to include 113 measures across 21 topic areas, and the web tool was modernized to enhance its key features and functionalities, including standardized indicator definitions; interactive charts, graphs, and maps that present data in a visually appealing format; an easy-to-use web-based interface for users to query and extract the data they need; and state comparison reports to identify geographic variations in disease and risk factor prevalence. National and state-level estimates are provided for the overall population and, where applicable, by sex, race and ethnicity, and age. We review the history of CDIs, describe the 2022-2024 refresh process, and explore the interactive features of the CDI web tool with the goal of demonstrating how practitioners, policymakers, and other users can easily examine and track a wide range of key indicators of chronic diseases and their risk factors to support state-level public health action.

Risk of Chronic Obstructive Pulmonary Disease and Receipt of a Breathing Test in 26 States and the District of Columbia, 2017-2018.

We estimated the prevalence of respiratory symptoms, chronic obstructive pulmonary disease (COPD) risk level, and receipt of a breathing test among adults without reported COPD in 26 states and the District of Columbia by using 2017-2018 Behavioral Risk Factor Surveillance System data. Among adults without reported COPD, the 3 respiratory symptoms indicating COPD (chronic cough, phlegm or mucus production, shortness of breath) were common (each >10%). About 15.0% were at higher COPD risk (based on the number of symptoms, age, and smoking status); 41.4% of adults at higher risk reported receipt of a breathing test. Patient-provider recognition and communication of risk symptoms, appropriate screening, and follow-up are important for early diagnosis and treatment.

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.

Trends in the Prevalence of Chronic Obstructive Pulmonary Disease Among Adults Aged ≥18 Years - United States, 2011-2021.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States. Overall COPD prevalence declined during 1999-2011. Trends in COPD prevalence during the previous decade have not been reported. CDC analyzed 2011-2021 Behavioral Risk Factor Surveillance System data to assess trends and differences in self-reported physician-diagnosed COPD prevalence among U.S. adults aged ≥18 years. Age-standardized prevalence of COPD did not change significantly from 2011 (6.1%) to 2021 (6.0%). Prevalence was stable for most states and subgroups; however, it decreased significantly among adults aged 18-44 years (average annual percent change [AAPC] = -2.0%) and increased significantly among those aged ≥75 years (AAPC = 1.3%), those living in micropolitan counties (0.8%), and among current (1.5%) or former (1.2%) smokers. COPD prevalence remained elevated in the following groups: women, adults aged ≥65 years, those with a lower education level, unable to work, living in rural areas, and who ever smoked. Evidence-based strategies, especially those tailored for adults disproportionately affected, can reduce COPD prevalence, and address the continued need for prevention, early diagnosis, treatment, and management.

Linking Local-Level Chronic Disease and Social Vulnerability Measures to Inform Planning Efforts: A COPD Example.

INTRODUCTION: Data are publicly available to identify geographic differences in health outcomes, including chronic obstructive pulmonary disease (COPD), and social vulnerability; however, examples of combining data across sources to understand disease burden in the context of community vulnerability are lacking. METHODS: We merged county and census tract model-based estimates of COPD prevalence from PLACES (www.cdc.gov/PLACES) with social vulnerability measures from the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (https://www.atsdr.cdc.gov/placeandhealth/svi), including 4 themes (socioeconomic, household composition and disability, minority status and language, and housing type and transportation), and the overall Social Vulnerability Index (SVI). We used the merged data set to create vulnerability profiles by COPD prevalence, explore joint geographic patterns, and calculate COPD population estimates by vulnerability levels. RESULTS: Counties and census tracts with high COPD prevalence (quartile 4) had high median vulnerability rankings (range: 0-1) for 2 themes: socioeconomic (county, 0.81; tract, 0.77) and household composition and disability (county, 0.75; tract, 0.81). Concordant high COPD prevalence and vulnerability for these themes were clustered along the Ohio and lower Mississippi rivers. The estimated number of adults with COPD residing in counties with high vulnerability was 2.5 million (tract: 4.7 million) for the socioeconomic theme and 2.3 million (tract: 5.0 million) for the household composition and disability theme (high overall SVI: county, 4.5 million; tract, 4.7 million). CONCLUSION: Data from 2 publicly available tools can be combined, analyzed, and visualized to jointly examine local COPD estimates and social vulnerability. These analyses can be replicated with other measures to expand the use of these cross-cutting tools for public health planning.

Insulin receptor substrate in brain-enriched exosomes in subjects with major depression: on the path of creation of biosignatures of central insulin resistance.

Insulin signaling is critical for neuroplasticity, cerebral metabolism as well as for systemic energy metabolism. In rodent studies, impaired brain insulin signaling with resultant insulin resistance (IR) modulates synaptic plasticity and the corresponding behavioral functions. Despite discoveries of central actions of insulin, in vivo molecular mechanisms of brain IR until recently have proven difficult to study in the human brain. In the current study, we leveraged recent technological advances in molecular biology and herein report an increased number of exosomes enriched for L1CAM, a marker predominantly expressed in the brain, in subjects with major depressive disorder (MDD) as compared with age- and sex-matched healthy controls (HC). We also report increased concentration of the insulin receptor substrate-1 (IRS-1) in L1CAM+ exosomes in subjects with MDD as compared with age- and sex-matched HC. We found a relationship between expression of IRS-1 in L1CAM+ exosomes and systemic IR as assessed by homeostatic model assessment of IR in HC, but not in subjects with MDD. The increased IRS-1 levels in L1CAM+ exosomes were greater in subjects with MDD and were associated with suicidality and anhedonia. Finally, our data suggested sex differences in serine-312 phosphorylation of IRS-1 in L1CAM+ exosomes in subjects with MDD. These findings provide a starting point for creating mechanistic framework of brain IR in further development of personalized medicine strategies to effectively treat MDD.

Geographic Differences in Sex-Specific Chronic Obstructive Pulmonary Disease Mortality Rate Trends Among Adults Aged ≥25 Years - United States, 1999-2019.

Chronic obstructive pulmonary disease (COPD) accounts for the majority of deaths from chronic lower respiratory diseases, the fourth leading cause of death in the United States in 2019.* COPD mortality rates are decreasing overall. Although rates in men remain higher than those in women, declines have occurred among men but not women (1). To examine the geographic variation in sex-specific trends in age-adjusted COPD mortality rates among adults aged ≥25 years, CDC analyzed 1999-2019 death certificate data, by urban-rural status,† U.S. Census Bureau region,§ and state. Among women, no significant change in overall COPD mortality occurred during this period; however, rates increased significantly in small metropolitan (average annual percent change [AAPC] = 0.6%), micropolitan (1.2%), and noncore (1.9%) areas and in the Midwest (0.6%). Rates decreased significantly in large central (-0.9%) and fringe metropolitan (-0.4%) areas (and in the Northeast (-0.5%) and West (-1.2%). Among men, rates decreased significantly overall (-1.3%), in all urban-rural areas (range = -1.9% [large central metropolitan] to -0.4% [noncore]) and in all regions (range = -2.0% [West] to -0.9% [Midwest]). Strategies to improve the prevention, treatment, and management of COPD are needed, especially to address geographic differences and improve the trend in women, to reduce COPD deaths.

Chronic Conditions Among Adults Aged 18─34 Years - United States, 2019.

Chronic conditions are common, costly, and major causes of death and disability.* Addressing chronic conditions and their determinants in young adulthood can help slow disease progression and improve well-being across the life course (1); however, recent prevalence estimates examining chronic conditions in young adults overall and by subgroup have not been reported. CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) to measure prevalence of 11 chronic conditions among adults aged 18-34 years overall and by selected characteristics, and to measure prevalence of health-related risk behaviors by chronic condition status. In 2019, more than one half (53.8%) of adults aged 18-34 years reported having at least one chronic condition, and nearly one quarter (22.3%) reported having more than one chronic condition. The most prevalent conditions were obesity (25.5%), depression (21.3%), and high blood pressure (10.7%). Differences in the prevalence of having a chronic condition were most noticeable between young adults with a disability (75.8%) and without a disability (48.3%) and those who were unemployed (62.3%) and students (45.8%). Adults aged 18-34 years with a chronic condition were more likely than those without one to report binge drinking, smoking, or physical inactivity. Coordinated efforts by public and private sectors might help raise awareness of chronic conditions among young adults and help improve the availability of evidence-based interventions, policies, and programs that are effective in preventing, treating, and managing chronic conditions among young adults (1).

Exploring Residents' Perceptions of Neighborhood Development and Revitalization for Active Living Opportunities.

INTRODUCTION: Community fears of gentrification have created concerns about building active living infrastructure in neighborhoods with low-income populations. However, little empirical research exists related to these concerns. This work describes characteristics of residents who reported 1) concerns about increased cost of living caused by neighborhood development and 2) support for infrastructural improvements even if the changes lead to a higher cost of living. METHODS: Data on concerns about or support for transportation-related and land use-related improvements and sociodemographic characteristics were obtained from the 2018 SummerStyles survey, an online panel survey conducted on a nationwide sample of US adults (n = 3,782). Descriptive statistics characterized the sample, and χ2 tests examined associations among variables. RESULTS: Overall, 19.1% of study respondents agreed that development had caused concerns about higher cost of living. Approximately half (50.7%) supported neighborhood changes for active living opportunities even if they lead to higher costs of living. Prevalences of both concern and support were higher among respondents who were younger and who had higher levels of education than their counterparts. Support did not differ between racial or ethnic groups, but concern was reported more often by Hispanic/Latino (28.9%) and other non-Hispanic (including multiracial) respondents (25.5%) than by non-Hispanic White respondents (15.6%). Respondents who reported concerns were more likely to express support (65.3%) than respondents who did not report concerns (47.3%). CONCLUSION: The study showed that that low-income, racial, or ethnic minority populations support environmental changes to improve active living despite cost of living concerns associated with community revitalization.

Comment: Sedation as part of secondary prophylaxis to prevent recurrent rheumatic fever in Aboriginal and Torres Strait Islander peoples: time for a reset?

Australia's national clinical practice guidelines recommend intramuscular (IM) penicillin every 28 days for persons diagnosed with an initial episode of acute rheumatic fever (ARF). This antibiotic coverage is initiated to reduce recurrent ARF episodes by preventing repeat infections with the causative bacterium, group A Streptococcus. Because disease has already occurred, this regimen is known as secondary prophylaxis (SP), done in order to prevent more episodes of ARF (known as recurrences). In 2020, eight authors shared with readers of Rural and Remote Health their experience of introducing off-label an oral, centrally acting, alpha agonist sedative to the prescribed SP regimen of IM penicillin for each of three Aboriginal children previously diagnosed with ARF. The living environments of the three children increased their risk for repeat group A Streptococcus infections and subsequent recurrences of ARF. We find the clinical case report perpetuates a troubling academic tone about this singular priority for SP. Injecting a child with IM penicillin appears to supersede all other objectives. Off-label sedation in remote settings is legitimised in order to succeed in this imperative. Those articles that peer-reviewed medical journals choose to publish privilege directions for priorities, policy and practice. In this commentary, we present alternative perspectives and initiatives for consideration.

Walking and Other Common Physical Activities Among Adults with Arthritis - United States, 2019.

The numerous health benefits of physical activity include reduced risk for chronic disease and improved mental health and quality of life (1). Physical activity can improve physical function and reduce pain and fall risk among adults with arthritis, a group of approximately 100 conditions affecting joints and surrounding tissues (most commonly osteoarthritis, fibromyalgia, gout, rheumatoid arthritis, and lupus) (1). Despite these benefits, the 54.6 million U.S. adults currently living with arthritis are generally less active than adults without arthritis, and only 36.2% of adults with arthritis are aerobically active (i.e., meet aerobic physical activity guidelines*) (2). Little is known about which physical activities adults with arthritis engage in. CDC analyzed 2019 Behavioral Risk Factor Surveillance System (BRFSS) data to examine the most common nonwork-related physical activities among adults with arthritis who reported any physical activity during the past month, nationally and by state. In 2019, 67.2% of adults with arthritis reported engaging in physical activity in the past month; among these persons, the most commonly reported activities were walking (70.8%), gardening (13.3%), and weightlifting (7.3%). In 45 U.S. states, at least two thirds of adults with arthritis who engaged in physical activity reported walking. Health care providers can help inactive adults with arthritis become active and, by encouraging physical activity and referring these persons to evidence-based physical activity programs, improve their health and quality of life.

Cross-sectional study of changes in physical activity behavior during the COVID-19 pandemic among US adults.

BACKGROUND: Physical activity (PA) provides numerous health benefits relevant to the COVID-19 pandemic. However, concerns exist that PA levels may have decreased during the pandemic thus exacerbating health disparities. This study aims to determine changes in and locations for PA and reasons for decreased PA during the pandemic. METHODS: Reported percentage of changes in and locations for PA and reasons for decreased PA were examined in 3829 US adults who completed the 2020 SummerStyles survey. RESULTS: Overall, 30% reported less PA, and 50% reported no change or no activity during the pandemic; percentages varied across subgroups. Adults who were non-Hispanic Black (Black) or Hispanic (vs. non-Hispanic White, (White)) reported less PA. Fewer Black adults (vs. White) reported doing most PA in their neighborhood. Concern about exposure to the virus (39%) was the most common reason adults were less active. CONCLUSIONS: In June 2020, nearly one-third of US adults reported decreased PA; 20% reported increased PA. Decreased activity was higher among Black and Hispanic compared to White adults; these two groups have experienced disproportionate COVID-19 impacts. Continued efforts are needed to ensure everyone has access to supports that allow them to participate in PA while still following guidance to prevent COVID-19 transmission.

Types of Physical Activity Recommended by Primary Care Providers for Patients at Risk for Cardiovascular Disease.

Primary care providers (PCPs) are uniquely positioned to promote physical activity for cardiovascular health. We sought to determine the types of physical activity that PCPs most often recommend to patients at risk for cardiovascular disease (CVD) and how these recommendations vary by PCPs' physical activity counseling practices. We examined the types of physical activity (walking, supervised exercise sessions, or other) PCPs most often suggested for CVD prevention among respondents to the 2018 DocStyles survey (N = 1,088). Most PCPs (80.0%) suggested walking to their patients at risk for CVD; however, PCPs who infrequently discussed physical activity with their patients at risk for CVD suggested walking less often than those who more frequently discussed physical activity. Walking is an easy and low-cost form of physical activity, and opportunities exist for certain PCPs to promote walking as part of their physical activity counseling practices for CVD prevention.

Associations between the National Walkability Index and walking among US Adults - National Health Interview Survey, 2015.

The Environmental Protection Agency created the National Walkability Index (Index) to compare and analyze walkability among US communities. Index elements include design, distance to transit, and diversity of land uses. Associations between the Index and walking behavior have not been examined. This study describes associations between the Index and transportation and leisure walking among US adults. Past week self-reported participation in transportation and leisure walking among adults (n = 33,672) was obtained from the 2015 Cancer Control Supplement of the National Health Interview Survey (NHIS) and analysis completed in 2019. Index scores were linked to NHIS data based on the respondent's residence and classified into least, below average, above average, and most walkable communities. Associations between Index categories and walking were examined with regression models. Overall, the Index was associated with a higher likelihood of walking, especially for transportation. Transportation walking was more common in areas with higher walkability (21.6%-51.6%, least to most walkable). Leisure walking was also more common with greater walkability (48.4%-56.5%, least to most walkable). Transportation and leisure walking by Index categories in urban areas were similar to the overall population; however, it was not associated with walking in rural areas. US adults living in more walkable areas report more transportation and leisure walking, especially among urban areas. Consistent with elements in the Index, associations were stronger for transportation than leisure walking. Findings support the use of the Walkability Index by researchers, professionals, and other relevant stakeholders as a viable indicator of walkability.

The Influence of Removing the Ten-Minute Bout Requirement on National Physical Activity Estimates.

The updated Physical Activity Guidelines for Americans (2nd edition) removes the requirement that physical activity should occur in bouts lasting 10 minutes or more to count toward the minimum aerobic guideline. Using self-reported data from the 2017 Behavioral Risk Factor Surveillance System (N = 386,960), we examined differences in national physical activity estimates with and without this requirement. Overall, 1.9% of adults reported activities in short bouts (<10 minutes). When excluding short bouts, 29.9% were inactive, 20.7% were insufficiently active, and 49.4% were active. When including short bouts, 29.1% were inactive, 21.4% were insufficiently active, and 49.5% were active. Eliminating the 10-minute-bout requirement had little effect on physical activity estimates.

Perceived Importance of Physical Activity and Walkable Neighborhoods Among US Adults, 2017.

The importance of physical activity and community-level promotion strategies are well established, but little is known about adult perception of the importance of physical activity. In a nationwide sample of US adults, we examined self-reported importance of regular physical activity and the importance of living in walkable neighborhoods. About 55% of adults strongly agreed that regular physical activity is important, 40% strongly agreed that living in a walkable neighborhood is important, and 31% strongly agreed that both are important. Separately for each measure, estimates were lower among adults with lower education levels and who did not meet the aerobic physical activity guideline. Opportunities exist to improve the perception of the importance of physical activity and the importance of walkable neighborhoods.

National-level environmental perceptions and walking among urban and rural residents: Informing surveillance of walkability.

Built environments that provide activity-friendly routes (e.g., sidewalks) to everyday destinations (e.g., shops) can increase physical activity. Surveillance of supports and destinations is important, and identifying which are associated with walking could prioritize surveillance questions. Our purpose was to identify the significant associations between supports and destinations with walking among a nationally-representative sample of urban- and rural-dwelling adults. Participants in the 2015 National Health Interview Survey, Cancer Control Supplement (n = 29,925) reported the near-home presence of walkable supports (roads, sidewalks, paths, or trails; sidewalks on most streets), destinations (shops; transit; movies, libraries, or churches; relaxing places), and past-week walking for leisure or transportation. We used stepwise logistic regression to quantify associations between supports and destinations and walking, including by urban/rural residence. We calculated the prevalence of walking across counts of reported elements by urban/rural residence. Among all participants, roads, sidewalks, paths, or trails and relaxing destinations were associated with leisure walking. Among urban residents, sidewalks on most streets and all four destination types were associated with transportation walking; among rural residents, roads, sidewalks, paths, or trails; movies, libraries, or churches; and relaxing destinations were associated with transportation walking. Walking was more common when more environmental elements were reported. To improve efficiency, communities may match surveillance priorities to behavioral priorities (i.e., leisure versus transportation walking) and environmental context (i.e., urban/rural areas). Surveillance of environments supporting leisure walking might focus on recreation-oriented spaces. Surveillance of environments supporting transportation walking might differ for urban and rural areas, and assessing destinations may be particularly important.

Prevalence of children walking to school and related barriers-United States, 2017.

Children and adolescents can engage in an active lifestyle by walking to school; however, several barriers may limit this behavior. This study estimates the prevalence of walking to school and related barriers as reported by U.S. parents. Data from the 2017 SummerStyles, a Web-based survey conducted on a nationwide sample of U.S. adults, were analyzed in 2017. Parents of children aged 5-18 years (n = 1137) were asked whether their youngest child walked to or from school during a usual school week and what barriers make this difficult. Frequencies are presented overall and by parent characteristics. About 1 in 6 parents (16.5%) reported their youngest child walks to or from school at least once during a usual week. Prevalence differed by parental race/ethnicity, marital status, region, and distance from school. The most common barrier was living too far away (51.3%), followed by traffic-related danger (46.2%), weather (16.6%), "other" barrier (14.7%), crime (11.3%), and school policy (4.7%). The frequency at which parents reported certain barriers varied by their child's walking status, distance to school, age of youngest child, race/ethnicity, education level, household income, and metropolitan statistical area status. However, the relative ranking of barriers did not differ by these characteristics. Prevalence of walking to school is low in the U.S., and living too far away and traffic-related danger are common barriers reported by parents. Implementing Safe Routes to School programs and other initiatives that utilize strategies to overcome locally-relevant barriers could help increase the prevalence of children walking to school.