Obesity Linked to Abnormalities in Brain Structure, Study Says

Obesity Linked to Abnormalities in Brain Structure, Study Says
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Obesity is associated with brain structural abnormalities in healthy individuals, as well as in those with major depressive disorder (MDD), a study has found.

The findings revealed that carrying a higher genetic risk for obesity is linked with reduced brain surface area.

The study, “Brain Structural Abnormalities in Obesity: Relation to Age, Genetic Risk, and Common Psychiatric Disorders. Evidence Through Univariate and Multivariate Mega-Analysis Including 6420 Participants From the ENIGMA MDD Working Group,” was published in the journal Molecular Psychiatry.

Obesity is one of the major public health problems in western countries, with an estimated prevalence of up to 38%.

Although normally associated with an increased risk of heart disease, obesity may also have a negative impact on brain structure and function, according to recent studies.

One of the most consistent findings seen across different studies is that obese individuals tend to have less brain gray matter, which is made of nerve cells and synapses — the sites where neurons communicate.

“However, even though these well-powered studies provide robust evidence for an association between BMI [body mass index] and brain structure in general, the current understanding of the relationship between obesity and brain structure is considerably limited,” the researchers wrote.

To explore the relationship between obesity and brain structural abnormalities, as well as the possible contribution of genetic factors, an international team examined genetic and brain imaging data from a large group of individuals who were part of the ENIGMA MDD Working Group.

The working group is a worldwide initiative to identify imaging markers that can distinguish MDD patients from healthy individuals.

This study was based on data from 6,420 individuals, including 3,519 healthy subjects (controls) and 2,901 MDD patients, who were recruited from 28 clinical sites.

Participants included both obese (BMI higher than 30 kg/m2) and normal weight individuals (BMI of 18.5–25 kg/m2).

While brain MRI scans were available for all participants, genetic data were available from a subset of 3,907 ENIGMA participants.

Statistical analyses found that obesity was strongly linked to structural abnormalities in the brain, particularly in its outer (cortical) and mid (subcortical) regions. This was true for both MDD patients and healthy individuals.

The most frequent structural defect linked to obesity was a reduction in the thickness of the brain cortex, which strongly resembled the type of structural abnormalities usually seen in people with different neuropsychiatric disorders.

The cortex is the outer region of the brain that controls functions such as speech, thought, and memory.

The researchers also discovered that age seemed to mediate the relationship between obesity and brain cortical thickness, with older individuals having the strongest reductions in cortical thickness driven by obesity.

In addition, individuals who were more predisposed genetically for obesity, as assessed by calculating a polygenic risk score, were also more likely to have lower brain surface area.

“The present findings demonstrate similar associations between obesity and brain structural abnormalities in healthy participants and depressive patients,” the investigators wrote, adding that the genetic and age-dependent effects may offer new insights on the origin of this association.

“Future (…) neuroimaging studies capable of providing higher resolution should aim to further delineate the precise regional distribution of obesity-related gray matter decrease,” they wrote.

Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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