Research Spotlights: October 2022

Time-restricted eating feasible and beneficial for cardiometabolic health among shift workers

Over a quarter of the U.S. workforce is comprised of shift workers. Those who work outside traditional work hours commonly include essential and frontline workers such as healthcare workers, emergency responders, and pilots. Shift workers often experience disruptions in sleep-activity and eating-fasting patterns, which are associated with chronic circadian disruptions, and in turn, increased risk for cardiometabolic disease, cancer, infections, and autoimmune diseases. Despite these documented risks, relatively few lifestyle interventions have been developed to improve the health for vulnerable shift work populations. Recently published research supported by the NIDDK, NCI, Federal Emergency Management Agency (FEMA), and others examined the feasibility and efficacy of a time-restricted eating (TRE) intervention for improving the health of firefighters who work 24-hour shifts. TRE is a behavioral intervention that limits time of daily caloric intake to a consistent window of 6 to 12 hours, without overly restricting energy (caloric) intake.

Researchers conducted The Healthy Heroes Study with first responders who work 24-hour shifts from the San Diego Fire-Rescue Department. Participants were randomized to either the TRE condition or the standard of care (SOC) condition. The SOC condition entailed nutritional counseling and following a Mediterranean diet, which encourages eating meals with others, uses olive oil as the main fat source, and contains primarily plant-based foods. 137 participants (136 male, 14 female, age range: 21-59 years) completed the 12-week intervention. All participants used the smartphone app myCircadianClock to log all food and drinks during 2 weeks of baseline and 12 weeks of intervention, and the app provided nudges and reminders. At baseline, participants in both conditions had a 95% eating window of approximately 14 hours (the interval of time that all caloric items were logged during a study period). In the TRE condition, participants were asked to select a 10-hour eating window that worked best for their work and social life. Participants in both conditions were assessed across several outcome measures including lipids, blood pressure, weight, BMI, and body composition, C-reactive protein, energy intake and activity, sleep, and quality of life.

Researchers found that, relative to the SOC condition, participants in the TRE condition had improved very-low-density lipoprotein size and quality of life. They also found that among participants with increased cardiometabolic risk at baseline, individuals in the TRE condition, but not in the SOC condition, showed significant decreases in HbA1c and diastolic blood pressure.

In summary, this TRE intervention was found to be both acceptable and efficacious among firefighters. This research highlights the need for more interventions that address the unique needs of shift workers to improve health, and potentially prevent cardiometabolic disease. The study findings have some limitations including a lack of gender diversity and the short length of the intervention (12 weeks), reliance upon self-report for some of the outcome measures (e.g., sleep), and relative heterogeneity of health at baseline. Future studies to address these limitations are needed to increase the utility and generalizability of this intervention.

Manoogian ENC, Zadourian A, Lo HC, Gutierrez NR, Shoghi A, Rosander A, Pazargadi A, Ormiston CK, Wang X, Sui J, Hou Z, Fleischer JG, Golshan S, Taub PR, Panda S. Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: The Healthy Heroes randomized control trial. Cell Metab. 2022 Oct 4;34(10):1442-1456.e7. doi: 10.1016/j.cmet.2022.08.018. PMID: 36198291; PMCID: PMC9536325.

Anxiety in pregnancy and the association with shorter gestational length

Anxiety is prevalent during pregnancy, with approximately 18% of women reporting elevated anxiety symptoms during their first trimester, 19% in the second trimester, and 25% in the third trimester. “Pregnancy anxiety” (also known as pregnancy-specific anxiety or prenatal anxiety) is an affective state where a pregnant woman experiences anxiety involving concerns and worries about her prenatal health, baby, labor, delivery, and/or future parenting. Pregnancy anxiety has been shown to be associated with adverse birth outcomes, including shorter gestation length/preterm birth, as well as negative early childhood outcomes, such as developmental delays, emotional or behavioral concerns, or cognitive difficulties. Less is known about whether timing of prenatal anxiety during pregnancy has an impact on birth outcomes, and the optimal timing for risk screening in women. Recently published research supported by the NICHD and NIDA aimed to enhance understanding of the predictive impact of the timing of risk screening on multiple measures of anxiety and distress in the first and third trimesters.

Study recruitment was conducted at prenatal practices and clinics located in two large urban medical centers in Denver and Los Angeles. A total of 196 pregnant women (mean age = 31 years), with a singleton pregnancy (approximately half of women were pregnant with their first child), and who spoke English or Spanish language were recruited into the study from 2013 to 2018. Study data was collected as part of a mixed-methods, longitudinal, prospective cohort study examining biological, psychological, obstetric, and developmental processes in women during pregnancy. Data collection occurred from women’s first trimester through 1 year postpartum, via structured interviews with study participants and data extraction from medical charts after birth. The research team used four standardized measures of anxiety, three of which were pregnancy specific. Data on several covariates was also collected, including information on maternal age, education, and risk factors during pregnancy or prior pregnancies such as severe infection, hypertension, diabetes, vascular risk factors, etc. The total number of risk factors for each participant was summed and then scores were mean-centered to create an obstetric risk index for study use.

Clinically significant anxiety was detected in approximately 12.8% of the study participants. The first goal of the study was to compare the ability of different measures of prenatal anxiety and distress to predict relative gestational length independent of obstetrical risk. The results showed that the participants' scores on all three pregnancy-related anxiety scales were interrelated, suggesting that the scales were measuring the same underlying phenomenon. The second study goal was to test the unique effects of each measure in the first and third trimesters, independent of the pregnancy anxiety latent factor. Researchers found that the pregnancy anxiety latent factor in the third trimester significantly predicted shorter gestational length after controlling for covariates. However, general anxiety in the first trimester also contributed to risk for early birth, indicating the possibility that general anxiety early in pregnancy could predispose women to be anxious later in pregnancy. These results remained the same when adjusted for the actual obstetrical risk.

In summary, this study adds to the body of evidence that pregnancy anxiety is a reliable risk indicator for shorter gestational length (i.e., earlier birth). Furthermore, these results suggest that doctors may want to screen for general anxiety early in pregnancy (first trimester), such as is often done for depression, so that those women that score high can be monitored and receive potential interventions later in pregnancy. Taken together, this body of evidence may help inform the most appropriate, targeted interventions that are feasible given a women’s stage of pregnancy, level of risk, and more practical clinical considerations (e.g., level of burden or potential duration and periodicity of intervention). This study had several limitations, including a lack of data collection during the second trimester, high variation in risk factors among the sample, or consideration of anxiety history in women. Despite these limitations, study findings make an important contribution to our understanding of the impact of pregnancy-specific anxiety, its severity, and impairment, and can inform the development, testing, and implementation of clinical interventions aimed at improving maternal and childbirth outcomes.

Dunkel Schetter C, Rahal D, Ponting C, Julian M, Ramos I, Hobel CJ, Coussons-Read M. Anxiety in pregnancy and length of gestation: Findings from the healthy babies before birth study. Health Psychol. 2022 Sep 26. doi: 10.1037/hea0001210. Epub ahead of print. PMID: 36154104.

New research shows how the brain differentially stores positive and negative memories

Is it possible to leverage the emotional valence of memories to treat certain disorders, such as post-traumatic stress disorder? In recent research supported by an NIH Early Independence Award (OD, NIMH), the NICHD, and others, researchers gain a better understanding of how the brain processes and stores emotional memories. Memories are stored in different areas across the brain, and individual memories exist as networks of cells known as engrams. In prior research, the ventral hippocampus (vHPC) has been shown to be important in the processing of emotion and valence. In the current study, the researchers sought to characterize the key molecular and genetic differences between positive and negative memories in the cells of the vHPC of mice.

The researchers used a combination of transgenic and all-virus based activity-dependent tagging strategies to visualize multiple valence-specific engrams in the vHPC. Using various behavioral paradigms, they demonstrated two partially segregated cell populations and projections that responded to appetitive and aversive experiences. Additionally, using RNA sequencing and DNA methylation sequencing approaches, they found that the appetitive and aversive engram cells exhibited different transcriptional programs and DNA methylation landscapes. Using optogenetic approaches, the researchers found that if they activated positive memory cells in the mice during a fear memory recall task, the competing positive memory “updated” the fear memory, reducing the behavioral fear response.

In summary, this study showed that the hippocampus contains discrete sets of cells that process aversive and appetitive memory engrams. Even though artificially activating memories in humans is not yet possible, these findings do have potential clinical implications since there are currently experimental therapeutics and techniques that strive to rewrite some of the traumatic components of negative experiences. Future studies are needed to further elucidate this phenomenon including understanding the contributions of environmental factors to memory engram formation. In conclusion, this study demonstrated that the hippocampus, in addition to processing spatio-temporal information, also contains discrete sets of cells that provide a biological substrate for multiple memory engrams.

Shpokayte M, McKissick O, Guan X, Yuan B, Rahsepar B, Fernandez FR, Ruesch E, Grella SL, White JA, Liu XS, Ramirez S. Hippocampal cells segregate positive and negative engrams. Commun Biol. 2022 Sep 26;5(1):1009. doi: 10.1038/s42003-022-03906-8. PMID: 36163262; PMCID: PMC9512908