Elevated body mass index might lead to lower cortical thickness, study finds

A Mendelian randomization study found that elevated body mass index might be a cause of lower cortical thickness. This was particularly prominent in the precentral and fusiform gyrus regions of the brain. The paper was published in Molecular Psychiatry.

Obesity is a chronic condition characterized by an excessive accumulation of body fat that can impair health and well-being. It is commonly assessed using body mass index, or BMI, which is calculated by dividing a person’s weight in kilograms by the square of their height in meters. A BMI between 25 and 30 suggests a person is overweight, while a BMI of 30 or more indicates obesity. Although BMI is useful for population-level screening, it is a rough measure that does not directly evaluate body fat or show how fat is distributed throughout the body.

Obesity develops through an interaction of genetic, biological, psychological, social, and environmental factors. In modern environments, high-calorie foods tend to be readily available while opportunities for everyday physical activity tend to be reduced. Studies provide evidence that diets based on foods rich in both easily digestible sugars and fats contribute heavily to weight gain. This is exactly the composition of many popular modern foods.

Obesity increases the risk of many adverse health conditions, such as type 2 diabetes, cardiovascular disease, sleep apnea, joint problems, and some cancers. It can also affect mental health and expose people to stigma and discrimination, which may reduce their quality of life.

Study author Jodie N. Painter and her colleagues note that previous research links obesity to certain structural changes in the brain. Until now, it was unknown whether these changes preceded obesity or were the consequences of weight gain. Fat tissue secretes proteins called pro-inflammatory cytokines that cause low-grade inflammation in individuals with obesity. The researchers suspected this inflammation could potentially lead to the observed adverse changes in the brain.

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The authors conducted a study using Mendelian randomization to see whether an elevated body mass index causes changes in the brain. The brain changes were measured as reduced cortical thickness, which refers to the depth of the brain’s outer layer of gray matter. Mendelian randomization is a research approach that uses naturally inherited genetic differences as proxies for environmental exposures. This helps scientists test whether an observed association is likely to reflect a direct cause-and-effect relationship.

This analysis was based on genome-wide association studies, which scan the entire genetic codes of large populations to find variations linked to specific traits. The genetic data for body mass index came from large international research consortiums that pool health information from hundreds of thousands of people. Specifically, the researchers used combined genetic data from up to 681,275 individuals of European ancestry. Data for the additional risk factors were drawn from other previously published genetic scans.

These additional factors included estimates of visceral fat, which is fat stored deep inside the belly around internal organs. The researchers also looked at fasting blood sugar, triglycerides, and high-density lipoprotein, a type of cholesterol that helps clear other cholesterols from the bloodstream. Finally, they included blood pressure and C-reactive protein, a substance that indicates the level of inflammation in the body.

Neuroimaging outcome data came from another massive international scientific collaborative group that studies the brain. This group provided genetic studies of global and regional cortical thickness in up to 23,183 individuals. The results showed that a higher body mass index was associated with lower average global cortical thickness. This association was particularly prominent in the precentral and fusiform gyrus regions of the brain.

The precentral gyrus controls voluntary movement, while the fusiform gyrus supports high-level visual recognition, especially of faces and words. More visceral fat and higher levels of the inflammatory blood marker C-reactive protein were also associated with lower cortical thickness. These associations tended to be stronger in areas where lower cortical thickness was already linked to a higher body mass index. In contrast, the researchers found very few associations between cortical thickness and blood pressure or metabolic blood markers.

The study authors concluded that their findings provide evidence for a causal effect of body mass index on lower cortical thickness. They recommend future research to explore how this effect on brain structure might increase the risk for neuropsychiatric conditions.

The study contributes to the scientific understanding of the structural brain changes induced by obesity. However, the scientists primarily investigated whether an elevated body mass index causes brain changes, rather than the reverse. A Mendelian randomization study like this can strengthen causal inferences but cannot provide definitive proof, as the research design depends on a number of assumptions.

The paper, “Deciphering the causal influence of BMI and related metabolic, inflammatory, and cardiovascular factors on brain structure: a Mendelian Randomization Study,” was authored by Jodie N. Painter, Alexander Refisch, Moritz Rau, Martin Walter, Scott Mackey, Jennifer Laurent, Paul M. Thompson, Katrina L. Grasby, Tomas Hajek, Sarah E. Medland, and Nils Opel.