Allostatic load and executive functions in overweight adults

Background/objective: Overweight is linked to inflammatory and neuroendocrine responses potentially prompting deregulations in biological systems harmful to the brain, particularly to the prefrontal cortex. This structure is crucial for executive performance, ultimately supervising behaviour. Thus, in the present work, we aimed to test the relationship between allostatic load increase, a surrogate of chronic physiological stress, and core executive functions, such as cognitive flexibility, inhibitory control, and working memory. Method Forty-seven healthy-weight and 56 overweight volunteers aged from 21 to 40 underwent medical and neuropsychological examination. Results: Overweight subjects exhibited a greater allostatic load index than healthy-weight individuals. Moreover, the allostatic load index was negatively related to inhibitory control. When separated, the link between allostatic load index and cognitive flexibility was more marked in the overweight group. Conclusions: An overweight status was linked to chronic physiological stress. The inverse relationship between the allostatic load index and cognitive flexibility proved stronger in this group. Set-shifting alterations could sustain rigid-like behaviours and attitudes towards food

Inflammatory agents partially explain associations between cortical thickness, surface area, and body mass in adolescents and young adulthood

Background/objectives Excessive body mass index (BMI) has been linked to a low-grade chronic inflammation state. Unhealthy BMI has also been related to neuroanatomical changes in adults. Research in adolescents is relatively limited and has produced conflicting results. This study aims to address the relationship between BMI and adolescents'brain structure as well as to test the role that inflammatory adipose-related agents might have over this putative link. Methods We studied structural MRI and serum levels of interleukin-6, tumor necrosis factor alpha (TNF-α), C-reactive protein and fibrinogen in 65 adolescents (aged 12-21 years). Relationships between BMI, cortical thickness and surface area were tested with a vertex-wise analysis. Subsequently, we used backward multiple linear regression models to explore the influence of inflammatory parameters in each brain-altered area. Results We found a negative association between cortical thickness and BMI in the left lateral occipital cortex (LOC) and the right precentral gyrus as well as a positive relationship between surface area and BMI in the left rostral middle frontal gyrus and the right superior frontal gyrus. In addition, we found that higher fibrinogen serum concentrations were related to thinning within the left LOC (β=−0.45,p< 0.001), while higher serum levels of TNF-αwere associated to a greater surface area in the right superior frontal gyrus (β=0.32,p=0.045). Besides, we have also identified a trend that negatively correlates the cortical thickness of the left fusiform gyrus with the increases in BMI. It was also associated to fibrinogen(β=−0.33,p=0.035). Conclusions These results suggest that adolescents'body mass increases are related with brain abnormalities in areas that could play a relevant role in some aspects of feeding behavior. Likewise, we have evidenced that these cortical changes were partially explained by inflammatory agents such as fibrinogen and TNF-α

Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their interaction with obesity

Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on almost all the executive variables, but no significant 'DRD4 7R-allele status' effects were observed for any of the executive variables analyzed. There was a significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions

Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status

Objective: Overweight (body mass index or BMI 25 kg/m2) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function

Allostatic load and disordered white matter microstructure in overweight adults

Overweight and stress are both related to brain structural abnormalities. The allostatic load model states that frequent disruption of homeostasis is inherently linked to oxidative stress and inflammatory responses that in turn can damage the brain. However, the effects of the allostatic load on the central nervous system remain largely unknown. The current study aimed to assess the relationship between the allostatic load and the composition of whole-brain white matter tracts in overweight subjects. Additionally, we have also tested for grey matter changes regarding allostatic load increase. Thirty-one overweight-to-obese adults and 21 lean controls participated in the study. Our results showed that overweight participants presented higher allostatic load indexes. Such increases correlated with lower fractional anisotropy in the inferior fronto-occipital fasciculi and the right anterior corona radiata, as well as with grey matter reductions in the left precentral gyrus, the left lateral occipital gyrus, and the right pars opercularis. These results suggest that an otherwise healthy overweight status is linked to long-term biological changes potentially harmful to the brain

Effect of the catechol‐ O ‐methyltransferase Val 158 Met polymorphism on theory of mind in obesity

International audienc

Functional network centrality in obesity: a resting-state and task fMRI study

Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention

Body mass index, systemic inflammation and cognitive performance in adolescents: A cross-sectional study

Background: Excessive body weight has been related to lower cognitive performance. One of the mechanisms through which excess body weight may affect cognition is inflammation. Hypothesis: Our hypothesis is that both body mass index (BMI) and circulating levels of inflammatory biomarkers will be negatively related to cognitive performance. Design: Cross-sectional study. Setting: Users of the public health centres of the Consorci Sanitari de Terrassa (Terrassa, Spain) between 2010 and 2017 aged 12-21 years. Participants: One hundred and five adolescents (46 normoweight, 18 overweight, 41 obese). Measurements: Levels of high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor α (TNFα) and fibrinogen were determined from blood samples. Cognitive performance was evaluated and six cognitive com posites were obtained: working memory, cognitive flexibility, inhibitory control, decision-making, verbal memory, and fine motor speed. A single multivariate general lineal model was used to assess the influence of the four inflammatory biomarkers, as well as participants' BMI, sex, and age on the 6 cognitive indexes. Results: An inverse relationship between BMI and inhibitory control (F = 5.688, p = .019; β = − 0.212, p = .031), verbal memory (F = 5.404, p = .022; β = − 0.255, p = .009) and fine motor speed (F = 9.038, p = .003; β = − 0.319, p = .001) was observed. Levels of TNFα and fibrinogen were inversely related to inhibitory control (F = 5.055, p = .027; β = − 0.226, p = .021) and verbal memory (F = 4.732, p = .032; β = − 0.274, p = .005), respectively. Limitations: The cross-sectional nature of the study, the use of cognitive tests designed for clinical purposes, and the use of BMI as a proxy for adiposity are limitations of our study that must be taken into account when interpreting results. Conclusions: Our data indicate that some components of executive functions, together with verbal memory, are sensitive to specific obesity-related inflammatory agents at early ages

Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their interaction with obesity

Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on almost all the executive variables, but no significant 'DRD4 7R-allele status' effects were observed for any of the executive variables analyzed. There was a significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions

Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status

Objective: Overweight (body mass index or BMI 25 kg/m2) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function