Shared brain connections associated with different psychiatric-linked behaviors across males and females

New research indicates that similar brain connection patterns can lead to different psychiatric behaviors in boys and girls during childhood. This suggests that there might be other factors (such as gender-related experiences or social influences) that cause differences in how males and females experience and show symptoms of psychiatric illnesses. The findings have been published in Biological Psychiatry.

“Sex and gender differences in the expression of psychiatric illnesses have been extensively characterized,” said study author Elvisha Dhamala, an assistant professor at the Institute of Behavioral Sciences at the Feinstein Institutes for Medical Research.

“Throughout the lifespan and across different illnesses, males are more likely to display externalizing behaviors while females are more likely to display internalizing behaviors. In this study, we wanted to look at whether these behavioral differences are driven by sex differences in the brain or some other factor(s), so we can better understand how to diagnose and treat these illnesses in a more personalized manner.”

The researchers used data from the Adolescent Brain Cognitive Development (ABCD) study, which is a large community-based sample of children and adolescents who were assessed on a comprehensive set of neuroimaging, behavioral, developmental, and psychiatric batteries.

The study included 5,260 children (2,689 males and 2,571 females; ages 9-10) from the ABCD 2.0.1 release. Quality control measures were used to ensure the imaging data’s quality, and participants were filtered based on the availability of functional MRI scans and behavioral scores. The researchers examined 17 behavioral scores derived from the Child Behavior Checklist and DSM-5. Linear regression models and deep learning algorithms were used to predict each behavioral score based on functional connectivity data.

The researchers found that functional connectivity profiles were able to predict externalizing behaviors in both boys and girls, but internalizing behaviors were generally only predictable in girls. Additionally, the study found that the same neural pathways were associated with both internalizing and externalizing behaviors in both boys and girls. These pathways included the default, limbic, control, and dorsal attention networks, which are all involved in higher-order cognitive and emotional processing.

“We show that the same patterns of brain connections underlie a wide range of internalizing and externalizing behaviors across the sexes,” Dhamala told PsyPost. “Based on this, we think that other sex- or gender-related factors might be driving the differences in how males and females experience and express psychiatric illnesses.”

Externalizing behaviors are characterized by the tendency to act out or express emotions and behaviors in an outward manner. These behaviors may include aggression, impulsivity, hyperactivity, substance abuse, and other behaviors that disrupt social norms..

On the other hand, internalizing behaviors are characterized by the tendency to turn emotions and behaviors inward. These behaviors may include anxiety, depression, withdrawal, self-harm, and other behaviors that are often hidden from others.

Both externalizing and internalizing behaviors are associated with various psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD), conduct disorder, anxiety disorder, depression, and others. Understanding the underlying neural mechanisms that contribute to these behaviors can aid in the development of targeted interventions and treatments.

“Going into this study, we weren’t sure whether shared or unique brain connections would be associated with these different behaviors across males and females,” Dhamala said. “We found it particularly interesting that it was the same set of connections implicated even though there were differences in the brain-behavior relationships themselves.”

But the researchers noted that as the children grow older and go through puberty, their behavior and brain biology may change, so the relationships between the brain and behavior may also change.

“These findings are based on a large community-based sample of children between the ages of 9 and 10,” Dhamala explained. “This is generally before puberty and before a lot of psychiatric illnesses emerge. In follow up studies, we’re hoping to repeat these analyses in adolescents and adults so we can determine how these brain-behavior relationships change throughout the lifespan.”

“It’s important to note that we did not consider gender in this study,” she added. “Sex and gender, while closely linked, are distinct from one another and both factors influence how we experience and express psychiatric illnesses. In future studies, we’re hoping to directly look at the relationships between sex, gender, and psychopathology so we can begin to disentangle the influences of sex and gender on psychiatric illnesses.”

The study, “Brain-based predictions of psychiatric illness-linked behaviors across the sexes“, was authored by Elvisha Dhamala, Leon Qi Rong Ooi, Jianzhong Chen, Jocelyn A. Ricard, Emily Berkeley, Sidhant Chopra, Yueyue Qu, Xihan Zhang, Connor Lawhead, B.T. Thomas Yeo, and Avram J. Holmes.

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