Study finds gender-specific brain patterns in children predisposed to substance use disorder

A new study has found differing patterns in the brain activity of boys and girls with a family history of substance use disorder, reflecting distinct ways in which they may be predisposed to addiction long before substance use begins.

Findings published in the journal Nature Mental Health “may help explain why boys and girls often follow different paths toward substance use and addiction”, said senior author Amy Kuceyeski, professor of mathematics and neuroscience in the department of radiology at Weill Cornell Medical College, US.

Researchers measured how the brain transitions between different patterns of activity during rest. Brain scans of nearly 1,900 children aged nine to eleven from the US’ ‘Adolescent Brain Cognitive Development’ study were analysed.

Girls with a family history of substance use disorders showed a higher transition energy in the brain’s default-mode network — which is at play during idle thinking or daydreaming — suggesting that their brains might need to work harder to shift gears from thought processes that are directed inwards.

“That may mean (a) greater difficulty disengaging from negative internal states like stress or rumination. Such inflexibility could set the stage for later risk, when substances are used as a way to escape or self-soothe,” first author Louisa Schilling, doctoral candidate at Weill Cornell Medical College, said.

However, boys with a family history showed a lower transition energy in the brain’s attention networks which regulate focus and response to external cues, the study found.

“Their brains seem to require less effort to switch states, which might sound good, but it may lead to unrestrained behaviour. They may be more reactive to their environment and more drawn to rewarding or stimulating experiences,” Kuceyeski said.

She added, “Girls may have a harder time stepping on the brakes, while boys may find it easier to step on the gas when it comes to risky behaviours and addiction.”

Since the brain differences were seen to appear before substance use began, the findings may indicate an inherited or early-life environmental vulnerability rather than the effects of drugs, the researchers said.

“Females with a family history showed higher (transition energy) in the default mode network, whereas males showed lower (transition energy) in dorsal and ventral attention networks,” the authors wrote.

The findings show how sex-specific influences of family history can impact brain dynamics and highlight the importance of biological sex when studying adolescent neurodevelopment and risk of substance use disorder.

“Recognising that boys and girls may travel different neural roads toward the same disorder can help tailor how we intervene. For example, programmes for girls might focus on coping with internal stress, while for boys the emphasis might be on attention and impulse control,” Kuceyeski said.