Maternal obesity and diabetes during pregnancy and early autism screening score at well-child visits in standard clinical practice.

LAY ABSTRACT: Early intervention and treatment can help reduce disability in children diagnosed with autism spectrum disorder. Screening for autism spectrum disorder in young children identifies those at increased likelihood of diagnosis who may need further support. Previous research has reported that exposure to maternal obesity and diabetes during pregnancy is associated with higher likelihood of autism spectrum disorder diagnosis in children. However, little is known about whether these maternal conditions are associated with how very young children score on autism spectrum disorder screening tools. This study examined associations between exposure to maternal obesity and diabetes during pregnancy and offspring scores on the Quantitative Checklist for Autism in Toddlers, an autism spectrum disorder screening questionnaire administered between 18-24 months at well-child visits. A higher score on the Quantitative Checklist for Autism in Toddlers suggests a higher likelihood of autism spectrum disorder; children with scores 3 or greater are referred to developmental pediatricians for evaluation. Our study found that children of mothers with obesity or diabetes during pregnancy had higher scores than children whose mothers did not have these conditions. Associations with maternal obesity and gestational diabetes diagnosed at or before 26 weeks of pregnancy were also present in children who did not have later autism spectrum disorder diagnoses, suggesting that exposure to these conditions during early pregnancy may be associated with a broad range of social and behavioral abilities. Identifying associations between maternal health conditions and early Quantitative Checklist for Autism in Toddlers screening scores could influence future screening and provision of support for children of mothers with these conditions.

Prenatal Exposure to Gestational Diabetes Mellitus is Associated with Mental Health Outcomes and Physical Activity has a Modifying Role.

Background: Studies suggest a link between prenatal gestational diabetes mellitus (GDM) exposure and poor mental health outcomes. We examined associations between prenatal GDM exposure and depressive and anxiety symptoms in children and assessed physical activity as a potential modifier of these associations. Method: Seventy children (AgeM(SD): 12(2.0), 56% GDM, 59% female) and their parents completed surveys: Center for Epidemiological Studies Depression Scale for Children (CES-DC), State-Trait Anxiety Inventory for Children (STAIC), Child Behavior Checklist (CBCL), and 3-day physical activity recall (3DPAR). Associations between mental health measures with GDM exposure and interactions between GDM exposure and child moderate-to-vigorous physical activity (MVPA) were assessed using regression. Results: GDM-exposed children had higher anxiety (p = 0.03) and internalizing symptoms (CBCL) (p = 0.04) than unexposed children. There was an interaction between GDM exposure and child MVPA on anxiety (p = 0.02), internalizing (p = 0.04) and externalizing symptoms (p = 0.004). In the low MVPA group, GDM exposed children had more depressive (p = 0.03), anxiety (p = 0.003), and internalizing symptoms (p = 0.03) than unexposed children. In the high MVPA group, there were no group differences except with externalizing symptoms (p = 0.04). Conclusion: Prenatal GDM is associated with higher anxiety and internalizing symptoms in children. Child MVPA modified the relationship between GDM exposure and mental health outcomes suggesting that physical activity during childhood could mitigate the negative mental health outcomes associated with prenatal GDM exposure.

Relationships between physical activity, healthy eating and cortical thickness in children and young adults.

Prior neuroimaging studies have shown associations between healthy lifestyle factors and cortical thickness; however, results on the direction of this association have been inconsistent. While the majority of studies were performed in older adults within specific weight status categories, little has been reported in younger populations with a range of adiposity, including groups with healthy-weight, overweight, and obesity. Here we investigated relationships between indices of physical activity (PA) and healthy eating with cortical thickness in children and youth/young adults and examined whether these relationships differed by weight status and age groups. Study participants included 119 youth/young adults and 159 children. We hypothesized that greater levels of PA and/or healthy eating index (HEI) composite scores would be positively associated with cortical thickness, and that this association would differ in overweight or obese groups versus normal weight groups, as well as youth/young adults vs. child cohorts. Overall PA (minutes/day) was assessed using 24-hour PA recalls. HEI was calculated to assess diet quality. A structural MRI was performed, and FreeSurfer 6.0 was used to assess cortical thickness in 68 regions of interest (ROI). Mixed effects modeling was performed to investigate associations of PA or HEI with cortical thickness. FDR corrections were applied for multiple ROIs. PA was positively associated with cortical thickness in the caudal middle frontal cortex (FDR adjusted p = 0.042) and cuneus cortex (FDR adjusted p = 0.017) after controlling for sex, age group, and weight status. When stratified by age, in youth/young adults, higher time spent in PA was associated with greater cortical thickness in the frontal, temporal, parietal and occipital cortex, after adjusting for sex and weight group (FDR adjusted ps < 0.05). No significant associations between PA and cortical thickness were observed in children. No significant associations between PA and cortical thickness were observed when stratified by weight group. No significant associations between HEI and cortical thickness were observed. These results indicate that higher time spent in PA is associated with greater cortical thickness, a relationship that appears to be stronger during youth/young adulthood and may be related to more favorable brain health outcomes.

Time-Varying Associations Between Device-Based and Ecological Momentary Assessment-Reported Sedentary Behaviors and the Concurrent Affective States Among Adolescents: Proof-of-Concept Study.

BACKGROUND: Previous studies on affective state-sedentary behavior (SB) associations have not accounted for their potentially time-varying nature and have used inconsistent SB measurement modalities. We investigated whether the strength of the associations between affective states and SB varied as a function of the time of day and by SB measurement modality (device-measured SB vs ecological momentary assessment-reported screen-based SB) in youth. OBJECTIVE: This study aimed to establish a proof of concept that SB-affective state associations may not be static during the day. In addition, we aimed to inform the methodology of future work, which may need to model associations as functions of the time of day and carefully consider how SB is operationalized or measured. METHODS: A total of 15 adolescents (age: mean 13.07, SD 1.03 years; 10/15, 67% female; 6/15, 40% Hispanic; 10/15, 67% healthy weight) wore thigh-mounted activPAL accelerometers and simultaneously reported their screen-based SBs and concurrent positive and negative affective states via ecological momentary assessment for 7 to 14 days (N=636 occasions). Time-varying effect models (varying slopes) examined how each measure of SB was associated with concurrent affective states from 7 AM to 8 PM. RESULTS: Time-varying effect model plots revealed that these associations varied in strength throughout the day. Specifically, device-based SB was related to greater concurrent negative affect only after approximately 5 PM and was unrelated to concurrent positive affect. Screen-based SB was related to greater concurrent negative affect only from 7 AM to approximately 9 AM. This was also related to greater concurrent positive affect from 7 AM to approximately 9:30 AM and from approximately 3 PM to approximately 7 PM. CONCLUSIONS: We provide preliminary evidence to suggest that future confirmatory studies investigating the SB-affective state relationship should consider the time-varying nature of these associations and SB measurement modality. There may be critical time windows when specific types of SBs co-occur with affect, suggesting that interventions may need tailoring to the time of day and type of SB if future studies using similar methodologies can replicate our findings.

FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans.

OBJECTIVE: This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans. METHODS: A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m2 ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging. RESULTS: Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (ß = -7.63, p = 0.03). This association was greatest among persons with healthy weight (ß = -15.70, p = 0.007) and was attenuated in people with overweight (ß = -4.00, p = 0.63) and obesity (ß = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (ß = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (ß = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05). CONCLUSIONS: These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.

Brain responses to glucose ingestion are greater in children than adults and are associated with overweight and obesity.

OBJECTIVE: This study investigated whether brain regions involved in the regulation of food intake respond differently to glucose ingestion in children and adults and the relationship between brain responses and weight status. METHODS: Data included 87 children (ages 7-11 years) and 94 adults (ages 18-35 years) from two cohorts. Healthy weight, overweight, and obesity were defined by Centers for Disease Control and Prevention criteria. Brain responses to glucose were determined by measuring cerebral blood flow using arterial spin labeling magnetic resonance imaging in brain regions involved in the regulation of eating behavior. RESULTS: Children showed significantly larger increases in brain responses to glucose than adults in the dorsal striatum (p < 0.01), insula (p < 0.01), hippocampus (p < 0.01), and dorsal-lateral prefrontal cortex (p < 0.01). Responses to glucose in the dorsal striatum (odds ratio [OR] = 1.52, 95% CI 1.05-2.20; p = 0.03), hippocampus (OR = 1.51, 95% CI: 1.02-2.22; p = 0.04), insula (OR = 1.64, 95% CI: 1.11-2.42; p = 0.01), and orbitofrontal cortex (OR = 1.63 95% CI: 1.12-2.39; p = 0.01) were positively associated with overweight or obesity, independent of age group. CONCLUSIONS: Children have greater brain responses to glucose ingestion than adults in regions involved in eating behavior, and these responses are associated with weight status.

Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.

Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, ß, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, ß, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, ß, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, ß, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, ß, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, ß, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, ß, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, ß, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, ß, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, ß, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, ß, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, ß, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, ß, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, ß, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (ß, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (ß, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.

Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus.

Prior epidemiological studies have found that in utero exposure to gestational diabetes mellitus (GDM) is associated with increased risk for neurodevelopmental disorders. However, brain alterations associated with GDM are not known. The hippocampus is pivotal for cognition and emotional regulation. Therefore, we assessed relationships between in utero exposure to GDM and hippocampal morphology and subfield structure during childhood. One hundred seventeen children aged 7-11 years (57% girls, 57% exposed to GDM), born at Kaiser Permanente Southern California, participated in the BrainChild Study. Maternal GDM status was determined from electronic medical records. Children underwent brain magnetic resonance imaging. Freesurfer 6.0 was used to measure hippocampal and individual hippocampal subfield gray matter volume (mm3 ). Morphological analyses on the hippocampal surface were carried out using shape analysis. GDM-exposed children exhibited reduced radial thickness in a small, spatially-restricted portion of the left inferior body of the hippocampus that corresponds to the CA1 subfield. There was a significant interaction between GDM-exposure and sex on the right hippocampal CA1 subfield. GDM-exposed boys had reduced right CA1 volume compared to unexposed boys, but this association was no longer significant after controlling for age. No significant group differences were observed in girls. Our results suggest that GDM-exposure impacts shape of the left hippocampal CA1 subfield in both boys and girls and may reduce volume of right hippocampal CA1 only in boys. These in-depth findings illuminate the unique properties of the hippocampus impacted by prenatal GDM-exposure and could have important implications for hippocampal-related functions.

Child physical activity as a modifier of the relationship between prenatal exposure to maternal overweight/obesity and neurocognitive outcomes in offspring.

BACKGROUND/OBJECTIVES: With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring. SUBJECTS/METHODS: One hundred children (59% girls) age 7-11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD. RESULTS: The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA. CONCLUSIONS: Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.

BMI status and associations between affect, physical activity and anxiety among U.S. children during COVID-19.

BACKGROUND: There is concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children, but to date, studies on mental health during the pandemic in children are limited. Furthermore, unprecedented lifestyle stressors associated with the pandemic may aggravate the childhood obesity epidemic, but the role of BMI on child activity levels and psychological outcomes during COVID-19 is unknown. OBJECTIVES: We investigated how emotional responses (positive/negative affect), physical activity (PA) and sedentary behaviours related to anxiety among U.S. children with healthy weight and overweight/obesity during the pandemic. METHODS: Sixty-four typically developing children (63% girls, 53% healthy weight) aged 9 to 15 years completed two virtual visits during the height of 'stay-at-home' measures from April 22 to July 29, 2020. Children completed 24-hours PA recalls, state portion of State-Trait Anxiety Inventory for Children and the 10-item Positive and Negative Affect Schedule for Children. RESULTS: Independent of child BMI status, child anxiety scores were over five standard deviations greater than normative values from paediatric populations prior to the pandemic. Higher positive affect and PA were each associated with reduced anxiety levels in children with overweight/obesity, whereas higher positive affect was associated with reduced anxiety in children with healthy weight. Greater leisure screen time was associated with higher negative affect irrespective of child BMI status. CONCLUSIONS: These associations highlight the potential mental health benefits of maintaining positive affect, engaging in PA and limiting leisure screen time for children during the pandemic and suggest that these associations may be particularly relevant for children with overweight/obesity.

Appetite-Regulating Hormones Are Reduced After Oral Sucrose vs Glucose: Influence of Obesity, Insulin Resistance, and Sex.

CONTEXT: Fructose compared to glucose has adverse effects on metabolic function, but endocrine responses to oral sucrose vs glucose is not well understood. OBJECTIVE: We investigated how oral sucrose vs glucose affected appetite-regulating hormones, and how biological factors (body mass index [BMI], insulin sensitivity, sex) influence endocrine responses to these 2 types of sugar. DESIGN: Sixty-nine adults (29 men; 23.22 ±â€…3.74 years; BMI 27.03 ±â€…4.96 kg/m2) completed the study. On 2 occasions, participants consumed 300-mL drinks containing 75 g of glucose or sucrose. Blood was sampled at baseline, 10, 35, and 120 minutes post drink for plasma glucose, insulin, glucagon-like peptide (GLP-1)(7-36), peptide YY (PYY)total, and acyl-ghrelin measures. Hormone levels were compared between conditions using a linear mixed model. Interaction models were performed, and results were stratified to assess how biological factors influence endocrine responses. RESULTS: Sucrose vs glucose ingestion provoked a less robust rise in glucose (P < .001), insulin (P < .001), GLP-1 (P < .001), and PYY (P = .02), whereas acyl-ghrelin suppression was similar between the sugars. We found BMI status by sugar interactions for glucose (P = .01) and PYY (P = .03); obese individuals had smaller increases in glucose and PYY levels after consuming sucrose vs glucose. There were interactions between insulin sensitivity and sugar for glucose (P = .003) and insulin (P = .04), and a sex by sugar interaction for GLP-1 (P = .01); men demonstrated smaller increases in GLP-1 in response to oral sucrose vs glucose. CONCLUSION: Sucrose is less efficient at signaling postprandial satiation than glucose, and biological factors influence differential hormone responses to sucrose vs glucose consumption.

Prenatal exposure to gestational diabetes is associated with anxiety and physical inactivity in children during COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is associated with adverse child mental health outcomes and reduced physical activity. Moreover, prenatal exposure to gestational diabetes (GDM) is associated with increased risk for adverse psychological outcomes in children. OBJECTIVES: Assess prenatal exposure to GDM on anxiety levels and physical activity in children during the COVID-19 pandemic. METHODS: Sixty-five children age 9 to 15 reported their physical activity and anxiety levels using the 24-hours physical activity recall and the State-Trait Anxiety Inventory for Children via phone or video meetings. Prenatal exposure to GDM was obtained from maternal electronic medical records. RESULTS: The 38 GDM-exposed children reported significantly higher anxiety levels and were less likely to engage in any vigorous physical activity (VPA) (5% vs 30%) compared to the 27 GDM-unexposed children. Lower levels of physical activity were significantly associated with higher levels of anxiety. Less engagement in VPA explained 75% of the association between GDM exposure and anxiety levels. CONCLUSIONS: Engaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly amongst GDM-exposed children.

Associations between Affect, Physical Activity, and Anxiety Among US Children During COVID-19.

We investigated how emotional responses (positive and negative affect), physical activity (PA), and sedentary behaviors related to anxiety among US children during the COVID-19 pandemic. Sixty-four typically-developing children (63% girls) age 9-15 years old completed two virtual visits during height of "stay-at-home" measures between April 22 - July 29, 2020. Children completed 24-hour PA recalls, state portion of State-Trait Anxiety Inventory for Children (STAIC), and the shortened 10-item Positive and Negative Affect Schedule for Children (PANAS-C). Children reported state anxiety scores that were more than 5 standard deviations greater than values from healthy pediatric populations prior to the pandemic. Children with higher positive affect and who reported more time in PA reported less state anxiety. Sedentary and leisure screen time were positively correlated with negative affect. Our findings suggest that maintaining positive affect, engaging in PA, and limiting leisure screen time may be important for child mental health during stressful periods. STATEMENT OF RELEVANCE: There is increasing concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children. To date, studies on mental health during the pandemic in children are limited. We investigated links between activity levels and psychological outcomes in children during the height of the "stay-at-home" measures. We found that children had anxiety scores that were more than 5 standard deviations greater than normative values from healthy pediatric populations prior to the pandemic, and 94% of children exceeded the American Academy of Pediatrics recommendations on leisure screen time. Positive affect and physical activity were associated with reduced anxiety levels in children during the pandemic. These findings highlight the important mental health benefits of maintaining positive affect, engaging in physical activity, and limiting leisure screen time for children, especially during stressful periods.

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood.

In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7-11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of added sugars and the monosaccharide, glucose, on the same brain measures. We found that increased dietary intake of fructose, measured as a percentage of total calories, was associated with both an increase in the volume of the CA2/3 subfield of the right hippocampus and increased axial, radial, and mean diffusivity in the prefrontal connections of the right cingulum. These findings are consistent with the idea that increased fructose consumption during childhood may be associated with an inflammatory process, and/or decreases or delays in myelination and/or pruning. Increased habitual consumption of glucose or added sugar in general were associated with an increased volume of right CA2/3, but not with any changes in the connectivity of the hippocampus. These findings support animal data suggesting that higher dietary intake of added sugars, particularly fructose, are associated with alterations in hippocampal structure and connectivity during childhood.

Contributions of Prenatal Exposures and Child Lifestyle to Insulin Sensitivity.

CONTEXT: Prenatal exposures and lifestyle factors are important for metabolic health. OBJECTIVE: Determine how prenatal exposures to maternal obesity and/or gestational diabetes mellitus (GDM) and childhood lifestyle factors independently contribute to child insulin sensitivity. DESIGN AND PARTICIPANTS: Ninety children aged 7 to 11 years (56% girls, 60% exposed to GDM), born at Kaiser-Permanente Southern California, completed an oral glucose tolerance test (OGTT) as part of the BrainChild Study. Matsuda insulin sensitivity index (ISI) was used to estimate insulin sensitivity. Participants completed two 24-hour dietary recalls, and daily energy intake (EI), dietary added sugar, and total sugar were calculated. The 3-day physical activity recall determined the average minutes per day of moderate to vigorous physical activity (MVPA) and the average minutes per day spent sedentary. Maternal prepregnancy body mass index (BMI) and GDM status were extracted from electronic medical records. MAIN OUTCOME MEASURE: Matsuda-ISI. RESULTS: Linear regression showed that children who spent more time in MVPA had better ISI (ß = 0.33; P = 0.001), and results remained after adjustment for maternal prepregnancy BMI, GDM exposure, child age, sex, daily EI, dietary added sugar (ß = 0.34; P = 0.001), and further adjustment for child adiposity (ß = 0.29; P = 0.001). Time spent sedentary, maternal prepregnancy BMI, GDM exposure, dietary added sugar, total sugar, and EI were not associated with ISI. CONCLUSIONS: Physical activity was the only predictor of ISI at this age, suggesting that engaging in physical activity during childhood is beneficial for insulin sensitivity and may ameliorate future risk for metabolic disease.

Sex differences in the association between prenatal exposure to maternal obesity and hippocampal volume in children.

INTRODUCTION: Animal studies have shown that male but not female offspring exposed to maternal obesity have abnormal hippocampal development. Similar sex differences were observed in animal models of developmental programming by prenatal stress or maternal diabetes. We aimed to translate this work into humans by examining sex-specific effects of exposure to maternal obesity on hippocampal volume in children. METHODS: Eighty-eight children (37 boys and 51 girls) aged 7-11 years completed the study. Maternal prepregnancy body mass index (BMI) was obtained from electronic medical records. A high-resolution anatomical scan was performed using a 3-Tesla magnetic resonance imaging (MRI) scanner. Total hippocampal volume and hippocampal subfield volumes were analyzed using FreeSurfer 6.0. Linear regression was used to investigate sex differences in relationships between maternal prepregnancy BMI and child hippocampal volume. RESULTS: Maternal prepregnancy BMI ranged from 19.0 to 50.4 kg/m2 . We observed a significant interaction between maternal prepregnancy BMI and sex on total hippocampal volume (p < .001) such that boys (r = -.39, p = .018) but not girls (r = .11, p = .45) had a significant negative relationship between maternal prepregnancy BMI and total hippocampal volume. This relationship in boys remained significant after adjusting for child and maternal covariates (ß = -126.98, p = .012). The sex interactions with prepregnancy BMI were consistently observed in hippocampal subfields CA1 (p = .008), CA2/3 (p = .016), CA4 (p = .002), dentate gyrus (p < .001), and subiculum (p < .001). CONCLUSIONS: Our results support findings in animal models and suggest that boys may be more vulnerable to the adverse effects of exposure to maternal obesity on hippocampal development than girls.

Anabolic-androgenic steroids and decision making: Probability and effort discounting in male rats.

Anabolic-androgenic steroid (AAS) abuse is implicated in maladaptive behaviors such as increased aggression and risk taking. Impaired judgment due to changes in the mesocorticolimbic dopamine system may contribute to these behavioral changes. While AAS are known to influence dopamine function in mesocorticolimbic circuitry, the effects on decision making are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water), and tested for cost/benefit decision making in two discounting paradigms. Rats chose between a small reward (1 sugar pellet) and a large discounted reward (3 or 4 pellets). Probability discounting (PD) measures sensitivity to reward uncertainty by decreasing the probability (100, 75, 50, 25, 0%) of receiving the large reward in successive blocks of each daily session. Effort discounting (ED) measures sensitivity to a work cost by increasing the lever presses required to earn the large reward (1, 2, 5, 10, 15 presses). In PD, testosterone-treated rats selected the large/uncertain reward significantly less than vehicle-treated controls. However, during ED, testosterone-treated rats selected the large/high effort reward significantly more than controls. These studies show that testosterone has divergent effects on different aspects of decision making. Specifically, testosterone increases aversion to uncertainty but decreases sensitivity to the output of effort for reward. These results have implications for understanding maladaptive behavioral changes in human AAS users.