Brain cortex structure linked to mental abilities and psychiatric disorders

The cerebral cortex, the outermost layer of the brain, is the central driver of various human capabilities, including decision-making, perception, language and memory. Understanding how the morphology (i.e., structure and shape) of people’s cerebral cortex is related to their mental health is a long-standing goal for many neuroscientists, as it could help to predict the risk that people will develop specific neuropsychiatric conditions while also contributing to their diagnosis and potentially informing their treatment.

Researchers at Maastricht University Medical Centre, Utrecht University and other institutes recently carried out a study aimed at unveiling causal relationships between cortical morphology and traits, including both neuropsychiatric conditions, behavioral patterns and metabolic traits. Their findings, published in Nature Mental Health, suggest that the total surface area (TSA) of the cerebral cortex and mean cortical thickness (MCT) contribute to people’s mental abilities and the development of some severe mental health disorders, respectively.

“Brain cortical morphology, indexed by its surface area and thickness, is known to be highly heritable,” wrote Bochao Danae Lin, Yunzhi Li and their colleagues in their paper. “Previous research has suggested a relationship of cortical morphology with several neuropsychiatric phenotypes. However, the multitude of potential confounders makes it difficult to establish causal relationships.”

As part of their study, the researchers analyzed a large amount of data sourced from a large genome-wide database, which was compiled as part of the Enhancing Neuro-Imaging Genetics through Meta-Analysis (ENIGMA) study. This is a brain-imaging study that collected brain imaging data, as well as psychiatric, psychological, behavioral and metabolic information from individuals living in 43 countries worldwide.

“We employ generalized summary-data-based Mendelian randomization and a series of sensitivity analyses to investigate causal links between 70 cortical morphology measures and 199 neuropsychiatric, behavioral and metabolic phenotypes,” wrote Lin, Li and their colleagues. “We show that total brain cortical surface area (TSA) has significant positive causal effects on 18 phenotypes.”

To analyze the data sourced from the ENIGMA database, Lin, Li and their colleagues employed a statistical technique called Mendelian randomization, which is useful for estimating causal relationships between traits while also controlling for potentially confounding factors. Their findings suggest that the TSA of the cerebral cortex is in fact causally related to some mental abilities, particularly their cognitive performance (i.e., how well they can memorize information, their ability to focus on specific tasks, their reasoning skills and other mental capabilities).

“The strongest effects include TSA positively influencing cognitive performance, while reverse analyses reveal small effects of cognitive performance on TSA,” wrote Lin, Li and their colleagues.

“Global mean cortical thickness (MTH) exhibits significant causal effects on five phenotypes, including schizophrenia. MTH reduces schizophrenia risk, and bidirectional causality is found between MTH and smoking initiation. Finally, in regional analyses, we detect positive influences of the transverse temporal surface area on cognitive performance and negative influences of transverse temporal thickness on schizophrenia risk.”

Overall, the results of the analyses performed by this team of researchers suggest that cortical morphology does in fact affect both people’s mental capabilities and neuropsychiatric traits. The causal relationships identified by Lin, Li and his colleagues could be explored further in future neuroscience studies, potentially helping to improve the early diagnosis and treatment of specific disorders, including schizophrenia and some cognitive deficits.

“Our results highlight bidirectional associations between TSA, MTH and neuropsychiatric traits,” wrote Lin, Li and their colleagues. “These insights offer potential avenues for intervention studies aimed at improving brain health.”

Written for you by our author Ingrid Fadelli, edited by Lisa Lock, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.

© 2025 Science X Network

The cerebral cortex, the outermost layer of the brain, is the central driver of various human capabilities, including decision-making, perception, language and memory. Understanding how the morphology (i.e., structure and shape) of people’s cerebral cortex is related to their mental health is a long-standing goal for many neuroscientists, as it could help to predict the risk that people will develop specific neuropsychiatric conditions while also contributing to their diagnosis and potentially informing their treatment.

Researchers at Maastricht University Medical Centre, Utrecht University and other institutes recently carried out a study aimed at unveiling causal relationships between cortical morphology and traits, including both neuropsychiatric conditions, behavioral patterns and metabolic traits. Their findings, published in Nature Mental Health, suggest that the total surface area (TSA) of the cerebral cortex and mean cortical thickness (MCT) contribute to people’s mental abilities and the development of some severe mental health disorders, respectively.

“Brain cortical morphology, indexed by its surface area and thickness, is known to be highly heritable,” wrote Bochao Danae Lin, Yunzhi Li and their colleagues in their paper. “Previous research has suggested a relationship of cortical morphology with several neuropsychiatric phenotypes. However, the multitude of potential confounders makes it difficult to establish causal relationships.”

As part of their study, the researchers analyzed a large amount of data sourced from a large genome-wide database, which was compiled as part of the Enhancing Neuro-Imaging Genetics through Meta-Analysis (ENIGMA) study. This is a brain-imaging study that collected brain imaging data, as well as psychiatric, psychological, behavioral and metabolic information from individuals living in 43 countries worldwide.

“We employ generalized summary-data-based Mendelian randomization and a series of sensitivity analyses to investigate causal links between 70 cortical morphology measures and 199 neuropsychiatric, behavioral and metabolic phenotypes,” wrote Lin, Li and their colleagues. “We show that total brain cortical surface area (TSA) has significant positive causal effects on 18 phenotypes.”

To analyze the data sourced from the ENIGMA database, Lin, Li and their colleagues employed a statistical technique called Mendelian randomization, which is useful for estimating causal relationships between traits while also controlling for potentially confounding factors. Their findings suggest that the TSA of the cerebral cortex is in fact causally related to some mental abilities, particularly their cognitive performance (i.e., how well they can memorize information, their ability to focus on specific tasks, their reasoning skills and other mental capabilities).

“The strongest effects include TSA positively influencing cognitive performance, while reverse analyses reveal small effects of cognitive performance on TSA,” wrote Lin, Li and their colleagues.

“Global mean cortical thickness (MTH) exhibits significant causal effects on five phenotypes, including schizophrenia. MTH reduces schizophrenia risk, and bidirectional causality is found between MTH and smoking initiation. Finally, in regional analyses, we detect positive influences of the transverse temporal surface area on cognitive performance and negative influences of transverse temporal thickness on schizophrenia risk.”

Overall, the results of the analyses performed by this team of researchers suggest that cortical morphology does in fact affect both people’s mental capabilities and neuropsychiatric traits. The causal relationships identified by Lin, Li and his colleagues could be explored further in future neuroscience studies, potentially helping to improve the early diagnosis and treatment of specific disorders, including schizophrenia and some cognitive deficits.

“Our results highlight bidirectional associations between TSA, MTH and neuropsychiatric traits,” wrote Lin, Li and their colleagues. “These insights offer potential avenues for intervention studies aimed at improving brain health.”

Written for you by our author Ingrid Fadelli, edited by Lisa Lock, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.

© 2025 Science X Network