Anny H. Xiang’s research while affiliated with Kaiser Permanente and other places

In this study, associations between prenatal exposure to fine particulate matter (PM2.5) from 9 sources and development of autism spectrum disorder (ASD) were assessed in a population-based retrospective pregnancy cohort in southern California. The cohort included 318,750 mother–child singleton pairs. ASD cases (N = 4559) were identified by ICD codes. Source-specific PM2.5 concentrations were estimated from a chemical transport model with a 4 × 4 km² resolution and assigned to maternal pregnancy residential addresses. Cox proportional hazard models were used to estimate the hazard ratios (HR) of ASD development for each individual source. We also adjusted for total PM2.5 mass and in a separate model for all other sources simultaneously. Increased ASD risk was observed with on-road gasoline (HR [CI]: 1.18 [1.13, 1.24]), off-road gasoline (1.15 [1.12, 1.19]), off-road diesel (1.08 [1.05, 1.10]), food cooking (1.05 [1.02, 1.08]), aircraft (1.04 [1.01, 1.06]), and natural gas combustion (1.09 [1.06, 1.11]), each scaled to standard deviation increases in concentration. On-road gasoline and off-road gasoline were robust for other pollutant groups. PM2.5 emitted from different sources may have different impacts on ASD. The results also identify PM source mixtures for toxicological investigations that may provide evidence for future public health policies.

Importance Data from surveys show increased mental health disorders in youths. However, little is known about clinical diagnosis over time. Objective To assess the incidence, prevalence, and changes from 2017 to 2021 for depression and anxiety diagnosed clinically among children, adolescents, and young adults and to identify potential disparities. Design, Setting, and Participants This cohort study included approximately 1.7 million individuals aged 5 to 22 years in Southern California. Data were extracted from electronic medical records; International Statistical Classification of Diseases, Tenth Revision ( ICD-10 ), codes were used to identify depression and/or anxiety diagnosis for each study year from January 1, 2017, to December 31, 2021. Rates were stratified by age, gender, race and ethnicity, estimated household income, weight status, and comorbidity history. Changes over time and association with these variables were assessed using Poisson regression. Data were analyzed between June 1, 2022, and November 29, 2023. Main Outcomes and Measures Clinical diagnosis of (1) depression and (2) anxiety without a depression diagnosis using ICD-10 codes. Results Among the 1.7 million participants, mean (SD) age was approximately 14 (5) years, and 51% were male. In terms of race and ethnicity for each study year, approximately 50% of participants were Hispanic; 8%, non-Hispanic Asian; 8%, non-Hispanic Black; and 23%, non-Hispanic White. From 2017 to 2021, depression diagnosis increased by 55.6% (from 1.35% to 2.10%) for incidence and 60.0% (from 2.55% to 4.08%) for prevalence; anxiety without depression diagnosis increased by 31.1% (from 1.77% to 2.32%) for incidence and 35.2% (from 3.13% to 4.22%) for prevalence ( P < .001 for trend). The increases in rates were higher during the COVID-19 pandemic (2020-2021) than before the pandemic (2017-2019), except for depression incidence. Rates increased across all subgroups. Rates were highest for subgroups aged 14 to 17 and 18 to 22 years; female participants; those of non-Hispanic American Indian or Alaska Native, non-Hispanic White, or multiple races or ethnicities; and subgroups with higher household income, obesity (and underweight for anxiety without depression), or comorbidities. Among these factors, age was the most important factor for depression diagnosis, whereas weight status was the most important factor for anxiety without depression diagnosis. Conclusions and Relevance This cohort study, using electronic medical record data from a large integrated health care system, found an increase in clinically diagnosed depression from 2017 to 2021, with a higher increase during the COVID-19 pandemic and higher rates in some subgroups. Equally important, this study identified high rates and an increase in clinical diagnosis of anxiety without a depression diagnosis. These results support the increased need in public health and health care effort to combat the mental health crisis in youths.

Objectives Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging (fMRI). Methods Participants were 90 children age 7–11 years (53 females) who underwent an fMRI-based visual food cue task in the fasted state. Hippocampal functional connectivity (FC) was examined using generalized psychophysiological interaction in response to food versus non-food cues. Hippocampal FC was compared between children with and without GDM exposure, while controlling for possible confounding effects of age, sex and waist-to-hip ratio. In addition, the influence of childhood and maternal obesity were investigated using multiple regression models. Results While viewing high caloric food cues compared to non-food cure, children with GDM exposure exhibited higher hippocampal FC to the insula and striatum (i.e., putamen, pallidum and nucleus accumbens) compared to unexposed children. With increasing BMI, children with GDM exposure had lower hippocampal FC to the somatosensory cortex (i.e., postcentral gyrus). Conclusions Intrauterine exposure to GDM was associated with higher food-cue induced hippocampal FC especially to reward processing regions. Future studies with longitudinal measurements are needed to clarify whether altered hippocampal FC may raise the risk of the development of metabolic diseases later in life.

Introduction: Sucralose is a non-caloric sweetener commonly consumed to provide sweet taste without calories. Yet, some studies suggest that non-caloric sweeteners stimulate appetite, possibly due to the delivery of a sweet taste without the post-ingestive metabolic signals that normally communicate with the hypothalamus to suppress hunger. We tested the hypothesis that acute consumption of the non-caloric sweetener, sucralose, would stimulate greater increases in hypothalamic blood flow, an MRI correlate of hunger, compared to caloric sugar (sucrose) and water, and would alter functional connectivity between the hypothalamus and other brain regions. Additionally, we expected sucrose, but not sucralose, to raise blood glucose levels, inversely affecting hypothalamic blood flow. We anticipated variations in hypothalamic responses based on weight status. Methods: Seventy-five young adults with healthy-weight, overweight, or obesity from a random-order crossover design study (NCT02945475) with acute consumption of a drink containing either 75g sucrose, sucralose (individually sweetness matched to sucrose), or plain water were included in this analysis to compare the effects of sucralose relative to sucrose and water on changes in hypothalamic blood flow, circulating glucose levels, and ratings of hunger. Hypothalamic blood flow (measured by pulsed arterial spin labeling perfusion MRI), hunger ratings, and glycemic responses were concurrently measured fasting, +10, and +35min after drink ingestion. As a secondary outcome, functional connectivity was performed using blood oxygen level-dependent (BOLD) fMRI to explore changes between the hypothalamus seed region and other brain areas after ingestion of sucralose relative to sucrose and water.Linear mixed-effects models were used for comparisons of drink contrasts. Linear regressions were used to examine associations between peripheral glucose levels, hypothalamic blood flow, and hunger ratings. Models were adjusted for age, sex, BMI, and race/ethnicity. Post hoc comparisons were adjusted for multiple comparisons using a Bonferroni correction. Results: There was a significant effect of drink on hypothalamic blood flow, adjusting for age, sex, BMI, and race/ethnicity (F = 5.05; p<.007). Compared to sucrose, intake of drinks sweetened with sucralose produced greater hypothalamic blood flow (Mean diff = .079, ± 0.03, p < .018) and greater hunger responses (Mean diff = .575 ± 0.16, p < .001). Sucralose vs water also increased hypothalamic blood flow (Mean diff = .078 ± 0.03, p < .019), but produced no difference in hunger ratings. Sucrose, but not sucralose, produced increases in peripheral glucose levels, which were associated with reductions in medial hypothalamic blood flow (beta =-.005 ± .002, p < .007). Sucralose, compared to sucrose and water, resulted in increased functional connections between the hypothalamus and brain regions involved in motivation and somatosensory processing. Conclusion: These results underscore the notable differences in sucralose, a non-caloric sweetener, on hypothalamic signaling pathways linked to appetite regulation when compared to sugar or water. The findings suggest that non-caloric sweeteners could affect key mechanisms in the hypothalamus responsible for appetite regulation.

Intrauterine exposure to gestational diabetes mellitus (GDM) is associated with an increased risk for adverse metabolic and cognitive outcomes, but the mechanisms are not clear. We tested the hypothesis that exposure to GDM is associated with changes in adiposity and brain trajectories during childhood to adolescence. Participants were 204 children (110 GDM exposed; 94 unexposed; 61% female; age 7-11 at baseline). Children underwent brain MRIs up to 4 times over 6 years. Adiposity measurements were obtained yearly over 6 years. Adiposity measures and FreeSurfer-derived brain volumes were compared between GDM-exposed and unexposed groups using mixed-effect models. We observed significant non-linear trajectories of BMI, body fat %, and waist circumference by age (all adjusted for sex and pubertal stage, p<0.0001) across all children. BMI (p=.058), body fat% (p<.049), and waist circumference (p<.015) trajectories varied by GDM exposure, with higher adiposity markers for GDM exposed vs unexposed. Compared to unexposed children, children exposed to GDM before 26 weeks had increased growth of total cortex (p<.009) and grey matter volume (p<.009), adjusted for age, sex, and pubertal stage, and multiple comparisons. Intrauterine exposure to GDM affects both adiposity and brain trajectories in transitioning from childhood to adolescence. These findings suggest a mechanistic link between GDM exposure and risk for adverse metabolic and neural outcomes. Disclosure S.P. Chakravartti: None. X. Gao: None. A. Xiang: None. K.A. Page: None. Funding American Diabetes Association (1-14-ACE 36); 1F31DK137584-01A1, R01DK116858, R01DK134079