A Mendelian randomization study found that increased BMI may be responsible for decreased cortical thickness. This was particularly pronounced in the precentral and fusiform gyrus regions of the brain. The paper was published in molecular psychiatry.
Obesity is a chronic disease characterized by excessive accumulation of body fat, which can impair health and well-being. It is commonly assessed using BMI. BMI is calculated by dividing a person’s weight in kilograms by the square of their height in meters. A BMI of 25 to 30 indicates overweight, and a BMI of 30 or above indicates obesity. Although BMI is useful for population-level screening, it is a rough measurement that does not directly assess body fat or indicate how fat is distributed throughout the body.
Obesity develops through the interaction of genetic, biological, psychological, social, and environmental factors. In modern environments, high-calorie foods are readily available, while opportunities for daily physical activity tend to decrease. Research shows evidence that diets based on foods rich in both easily digestible sugars and fats contribute significantly to weight gain. This is exactly the composition of many popular modern foods.
Obesity increases the risk of many harmful health conditions, including type 2 diabetes, cardiovascular disease, sleep apnea, joint problems, and some cancers. It can also affect mental health, expose people to prejudice and discrimination, and reduce their quality of life.
Study author Jodi N. Painter and her colleagues point out that previous research has linked obesity to certain structural changes in the brain. Until now, it was unclear whether these changes preceded obesity or were a result of weight gain. Adipose tissue secretes proteins called proinflammatory cytokines that cause mild inflammation in obese people. The researchers suspected that this inflammation could cause the harmful changes observed in the brain.
The authors conducted a study using Mendelian randomization to see if increasing BMI causes changes in the brain. Brain changes were measured as a decrease in cortical thickness, which refers to the depth of the outer layer of the brain’s gray matter. Mendelian randomization is a research approach that uses naturally inherited genetic differences as a proxy for environmental exposure. This helps scientists test whether observed associations may reflect direct causation.
This analysis is based on genome-wide association studies, which scan the entire genetic code of large populations to find variations associated with specific traits. Genetic data for BMI was provided by a large international research consortium that pools health information from hundreds of thousands of people. Specifically, the researchers used combined genetic data from up to 681,275 people of European descent. Additional risk factor data was extracted from other previously published genetic scans.
These additional factors include an estimate of visceral fat, which is fat stored deep in the abdomen around internal organs. The researchers also looked at fasting blood sugar, triglycerides, and high-density lipoproteins, a type of cholesterol that helps remove other cholesterol from the bloodstream. Finally, it included blood pressure and C-reactive protein, a substance that indicates the level of inflammation in the body.
The neuroimaging results data come from another large international scientific collaboration 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 higher BMI was associated with lower mean overall cortical thickness. This association was particularly pronounced in the precentral and fusiform gyrus regions of the brain.
The precentral gyrus controls voluntary movements, and the fusiform gyrus supports advanced visual recognition, especially of faces and words. Increased visceral fat and elevated levels of the inflammatory blood marker C-reactive protein were also associated with decreased cortical thickness. These associations tended to be stronger in regions where lower cortical thickness is already associated with higher BMI. In contrast, the researchers found little association between cortical thickness and blood pressure or metabolic blood markers.
The study authors concluded that their findings provide evidence for a causal role of BMI on reduced cortical thickness. They recommend future studies to investigate how this influence on brain structures increases the risk of neuropsychiatric disorders.
This study contributes to the scientific understanding of structural changes in the brain caused by obesity. However, the scientists primarily investigated whether increased BMI causes changes in the brain rather than the reverse. Although such Mendelian randomization studies can strengthen causal inferences, they cannot provide conclusive evidence because the study design relies on many assumptions.
The paper, “Deciphering the causal effects of BMI and associated metabolic, inflammatory, and cardiovascular factors on brain structure: a Mendelian randomization study,” was written by Jodie N. Painter, Alexander Refisch, Moritz Rau, Martin Walter, Scott Mackey, Jennifer Western, Paul M. Thompson, Katrina L. Grasby, Tomas Hajek, Sarah E. Medland, and Nils Opel.
