Combined effects of age and BMI are related to altered cortical thickness in adolescence and adulthood

Overweight and obesity are associated with functional and structural alterations in the brain, but how these associations change across critical developmental periods remains unknown. Here, we examined the relationship between age, body mass index (BMI) and cortical thickness (CT) in healthy adolescents (n = 70; 14–19 y) and adults (n = 75; 25–45 y). We also examined the relationship between adiposity, impulsivity, measured by delay discounting (DD), and CT of the inferior frontal gyrus (IFG), a region key to impulse control. A significant age-by- BMI interaction was observed in both adolescents and adults; however, the direction of this relationship differed between age groups. In adolescents, increased age-adjusted BMI Z-score attenuated age-related CT reductions globally and in frontal, temporal and occipital regions. In adults, increased BMI augmented age-related CT reductions, both globally and in bilateral parietal cortex. Although DD was unrelated to adiposity in both groups, increased DD and adiposity were both associated with reduced IFG thickness in adolescents and adults. Our findings suggest that the known age effects on CT in adolescence and adulthood are moderated by adiposity. The association between weight, cortical development and its functional implications would suggest that future studies of adolescent and adult brain development take adiposity into account.This work was supported by Wellcome Trust [project grant 206368/ Z/17/Z] (PCF), the Bernard Wolfe Health Neuroscience Fund (HZ, PCF) and the Andalusian Health Service (Consejeria de Salud) [project grant P-10-HUM-6635 (NEUROECOBE)] (AVG). MLW was supported by the Cambridge Trust and NIH-Oxford Cambridge Scholars Program

Prenatal exposure to maternal cigarette smoking, amygdala volume, and fat intake in adolescence

Context : Prenatal exposure to maternal cigarette smoking is a well-established risk factor for obesity, but the underlying mechanisms are not known. Preference for fatty foods, regulated in part by the brain reward system, may contribute to the development of obesity. Objective : To examine whether prenatal exposure to maternal cigarette smoking is associated with enhanced fat intake and risk for obesity, and whether these associations may be related to subtle structural variations in brain regions involved in reward processing. Design : Cross-sectional study of a population-based cohort. Setting : The Saguenay Youth Study, Quebec, Canada. Participants : A total of 378 adolescents (aged 13 to 19 years; Tanner stage 4 and 5 of sexual maturation), half of whom were exposed prenatally to maternal cigarette smoking (mean [SD], 11.1 [6.8] cigarettes/d). Main Outcome Measures : Fat intake was assessed with a 24-hour food recall (percentage of energy intake consumed as fat). Body adiposity was measured with anthropometry and multifrequency bioimpedance. Volumes of key brain structures involved in reward processing, namely the amygdala, nucleus accumbens, and orbitofrontal cortex, were measured with magnetic resonance imaging. Results : Exposed vs nonexposed subjects exhibited a higher total body fat (by approximately 1.7 kg; P = .009) and fat intake (by 2.7%; P = .001). They also exhibited a lower volume of the amygdala (by 95 mm3; P < .001) but not of the other 2 brain structures. Consistent with its possible role in limiting fat intake, amygdala volume correlated inversely with fat intake (r = −0.15; P = .006). Conclusions : Prenatal exposure to maternal cigarette smoking may promote obesity by enhancing dietary preference for fat, and this effect may be mediated in part through subtle structural variations in the amygdala

Impulsivity and body fat accumulation are linked to cortical and subcortical brain volumes among adolescents and adults

Obesity is associated not only with metabolic and physical health conditions, but with individual variations in cognition and brain health. This study examined the association between body fat (an index of excess weight severity), impulsivity (a vulnerability factor for obesity), and brain structure among adolescents and adults across the body mass index (BMI) spectrum. We used 3D T1 weighted anatomic magnetic resonance imaging scans to map the association between body fat and volumes in regions associated with obesity and impulsivity. Participants were 127 individuals (BMI: 18–40 kg/m2; M = 25.69 ± 5.15), aged 14 to 45 years (M = 24.79 ± 9.60; female = 64). Body fat was measured with bioelectric impendence technology, while impulsivity was measured with the UPPS-P Impulsive Behaviour Scale. Results showed that higher body fat was associated with larger cerebellar white matter, medial orbitofrontal cortex (OFC), and nucleus accumbens volume, although the latter finding was specific to adolescents. The relationship between body fat and medial OFC volume was moderated by impulsivity. Elevated impulsivity was also associated with smaller amygdala and larger frontal pole volumes. Our findings link vulnerability and severity markers of obesity with neuroanatomical measures of frontal, limbic and cerebellar structures, and unravel specific links between body fat and striatal volume in adolescence

A Behavioural Genetic Model of the Mechanisms Underlying the Link Between Obesity and Dimensional Measures of Attention-Deficit/Hyperactivity Disorder (ADHD)

Objective: The purpose of this study was to investigate genetic and psycho-behavioural mechanisms contributing to the strong ADHD symptom-obesity association. Genetic variants associated with hypo-dopaminergic functioning have been implicated in ADHD, particularly the 7-repeat allele of a VNTR located on the DRD4 gene, likely due to the receptor’s predominance in the prefrontal cortex. Based on this evidence, some experts have suggested that a shared aetiology of a dysfunctional dopamine (DA) system is responsible for the link. However, this conflicts with accumulating evidence that it is actually an amplified DA signal that increases the risk for overeating and weight gain due to a stronger appetitive response to food cues. It seems plausible that individuals with ADHD symptoms who are predisposed overeat are those who also possess a high sensitivity to, and greater motivation to seek out, rewarding stimuli, as reflected by increased DA availability in the brain reward pathways. Accordingly, the current study tested the hypothesis that symptoms of ADHD, predicted by hypo-dopaminergic functioning in the prefrontal cortex, in combination with an enhanced appetitive drive, predict hedonic eating, and in turn, higher BMI. Methods: Functional markers of the DRD2 and DRD4 were genotyped to determine their contributions to ADHD symptoms and various indices of hedonic eating, respectively. The model was tested using Structural Equation Modeling procedures in a general population sample (n=421 adults) representing a broad range of body mass index (BMI) values. Results: Overall, the fit indices indicated that the proposed model was a good fit to the data. Controlling for education level, all parameter estimates were in the expected direction and statistically significant with the exception of the pathway from the DRD4 marker to ADHD symptoms. The indirect effect was significant, indicating that overeating mediated the association between ADHD symptoms and BMI. Conclusions: Results lend support to the hypothesis that overeating and an elevated DA signal in the ventral striatum – representative of a greater reward response – are responsible for the link between ADHD symptoms and obesity. The current study was the first to connect the most prominent and supported theories of ADHD with evidence-based models of hedonic eating

Saguenay Youth Study : a multi-generational approach to studying virtual trajectories of the brain and cardio-metabolic health

This paper provides an overview of the Saguenay Youth Study (SYS) and its parental arm. The overarching goal of this effort is to develop trans-generational models of developmental cascades contributing to the emergence of common chronic disorders, such as depression, addictions, dementia and cardio-metabolic diseases. Over the past 10 years, we have acquired detailed brain and cardio-metabolic phenotypes, and genome-wide genotypes, in 1029 adolescents recruited in a population with a known genetic founder effect. At present, we are extending this dataset to acquire comparable phenotypes and genotypes in the biological parents of these individuals. After providing conceptual background for this work (transactions across time, systems and organs), we describe briefly the tools employed in the adolescent arm of this cohort and highlight some of the initial accomplishments. We then outline in detail the phenotyping protocol used to acquire comparable data in the parents

The Effects of Early Life Stress, Postnatal Diet Modulation, and Long-Term Western-Style Diet on Later-Life Metabolic and Cognitive Outcomes

Early life stress (ES) increases the risk to develop metabolic and brain disorders in adulthood. Breastfeeding (exclusivity and duration) is associated with improved metabolic and neurocognitive health outcomes, and the physical properties of the dietary lipids may contribute to this. Here, we tested whether early life exposure to dietary lipids mimicking some physical characteristics of breastmilk (i.e., large, phospholipid-coated lipid droplets; Concept Nuturis® infant milk formula (N-IMF)), could protect against ES-induced metabolic and brain abnormalities under standard circumstances, and in response to prolonged Western-style diet (WSD) in adulthood. ES was induced by exposing mice to limited nesting material from postnatal day (P) 2 to P9. From P16 to P42, male offspring were fed a standard IMF (S-IMF) or N-IMF, followed by either standard rodent diet (SD) or WSD until P230. We then assessed body composition development, fat mass, metabolic hormones, hippocampus-dependent cognitive function, and neurogenesis (proliferation and survival). Prolonged WSD resulted in an obesogenic phenotype at P230, which was not modulated by previous ES or N-IMF exposure. Nevertheless, ES and N-IMF modulated the effect of WSD on neurogenesis at P230, without affecting cognitive function, highlighting programming effects of the early life environment on the hippocampal response to later life challenges at a structural level

The driving forces of metabolic programming:a fundamental study in mice

Metabolic programming refers to the fact that environmental factors, such as diet, during the first 1000 days of life, may be able to establish a pathway of the metabolic profile later in life

The associations between sugar sweetened beverage intake, satiety, and metabolic health in minority youth

Non-Hispanic Black (NHB) and Hispanic children are at an increased risk of obesity and metabolic disease in the United States. Increasingly obesity is viewed as a multifaceted phenotype, beyond simply excess body weight. Research indicates that homeostatic mechanisms as well as hedonic systems are altered in obese individuals. The objective of this study was to examine how sugar sweetened beverage (SSB) intake, a highly modifiable dietary behavior, impacts both metabolic health and hedonic perceptions. This study is made up of three cross sectional analyses: the first two are secondary analyses of data from the University of Southern California, and the third was preformed at the University of Texas at Austin. The first examined the relationship between SSB intake, perceived hunger and satiety, and endocrine biomarkers in overweight and obese NHB and Hispanic adolescents (14-17 y). SSB intake of two servings or more per day was associated with decreased satiety and suppressed ghrelin compared to subjects that consumed one or less servings of SSB. The second examined the association between SSB intake, visceral fat accumulation (VAT), and cortisol awakening response (CAR) in a similar sample of 60 overweight and obese NHB and Hispanic adolescents (14-17y). SSB intake of two servings or more was associated with increased VAT and increased CAR compared to subjects that consumed one or less servings of SSB. The third examined the effect of SSB intake on reward pathways in the brain using functional magnetic resonance imaging (fMRI), as well as how free-living dietary and dietary intake at an ad libitum meal impacts hunger and metabolic biomarkers in 41 overweight and obese Hispanic children (7-10 y). Although analysis of the fMRI data was uninterruptable, increased hunger and decreased satiety at an ad libitum meal was related to added sugar intake greater than 10% of the subject’s daily calories. In adolescents, SSB intake is associated with decreased feelings of fullness and an unfavorable metabolic profile. In young children, added sugar intake is associated with appetite independent of homeostatic factors.Nutritional Science

Weight‐Related Differences in Salience, Default Mode, and Executive Function Network Connectivity in Adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156135/2/oby22853.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156135/1/oby22853_am.pd

Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction: Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Methods: Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Results: Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Conclusion: Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation