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The stress of pandemic lockdowns prematurely aged the brains of teenagers by at least three years and in ways similar to changes observed in children who have faced chronic stress and adversity, a study has found.

The study, published Thursday in <a href="https://www.bpsgos.org/article/S2667-1743(22)00142-2/fulltext" target=_blank>Biological Psychiatry: Global Open Science</a>, was the first to compare scans of the physical structures of teenagers’ brains from before and after the pandemic started, and to document significant differences, said Ian Gotlib, lead author on the paper and a psychology professor at Stanford University.

Researchers knew teens had higher “levels of depression, anxiety and fearfulness” than “before the pandemic. But we knew nothing about the effects on their brains,” said Gotlib, who is director of the Stanford Neurodevelopment, Affect, and Psychopathology Laboratory. “We thought there might be effects similar to what you would find with early adversity; we just didn’t realize how strong they’d be.”

By comparing MRI scans of a group of 128 children, half taken before and half at the end of the first year of the pandemic, the researchers found growth in the hippocampus and amygdala, brain areas that respectively control access to some memories and help regulate fear, stress and other emotions.

They also found thinning of the tissues in the cortex, which is involved in executive functioning. These changes happen during normal adolescent development; however, the pandemic appeared to have accelerated the process, Gotlib said.

Premature aging of children’s brains isn’t a positive development. Before the pandemic, it was observed in cases of chronic childhood stress, trauma, abuse and neglect. These <a href="https://www.cdc.gov/violenceprevention/aces/index.html">adverse childhood experiences</a> not only make people more vulnerable to depression, anxiety, addiction and other mental illnesses, they can raise the risk of cancer, diabetes, heart disease and other long-term negative outcomes.

The pre-pandemic images of teen brains came from a longitudinal study that Gotlib’s team began eight years ago, with the original goal of better understanding gender differences in depression rates among adolescents. The researchers recruited 220 children ages 9 to 13, with a plan to take MRI scans of their brains every two years. As they were collecting the third set of scans, the pandemic shut down all in-person research at Stanford, preventing the scientists from collecting brain scan data from March 2020 until late that year.

As they debated how to account for the disruption, the scientists saw an opportunity to investigate a different question: how the pandemic itself may have impacted the physical structure of the children’s brains and their mental health. They matched pairs of children with the same age and gender, creating subgroups with similar puberty, socioeconomic status and exposure to childhood stress. “That allowed us to compare 16-year olds before the pandemic with different 16-year olds assessed after the pandemic,” Gotlib said.

To determine the average brain age of their samples, the researchers fed their brain scans into a machine-learning model for predicting brain age developed by the ENIGMA-Brain Age working group, a collaboration among scientists who pool their brain image data sets. They also evaluated mental health symptoms reported by the matched pairs. They found more severe symptoms of anxiety, depression and internalizing problems in the group that had experienced the pandemic.

“The takeaway for me is that there are serious issues with mental health and kids around the pandemic,” Gotlib said. “Just because the shutdown ended doesn’t mean we’re fine.”

Prior <a href="https://jamanetwork.com/journals/jamapediatrics/fullarticle/2782796">research</a> has found dramatically higher levels of anxiety, depression, suicidality and other mental illnesses in adolescents since the onset of the pandemic.

The current study has important implications for other longitudinal imaging studies of adolescent brains, said Jason Chein, professor of psychology and neuroscience and the director of the Temple University Brain Research &amp; Imaging Center. “It has both methodological implications and potentially societally relevant implications,” Chein said.

Longitudinal studies of development that span the pandemic may yield findings that are tainted by the psychosocial impacts, so broad conclusions about development can’t be drawn, Chein said. And for society, the implications are that teenagers and young adults may need long-term, ongoing mental health and other support because this cohort may not be as advanced as expected based on just their chronological age.

He cautioned, however, against making broad interpretations based on the changes the researchers observed. “It’s pretty interesting that they observed this change,” he said. “But I’m reluctant to then jump to the conclusion that what it signals to us is that somehow we’ve advanced the maturation of the brains of kids.” In particular, brain regions can show nonlinear patterns of growth, so simply seeing a thinner cortex or larger amygdala volume doesn’t necessarily indicate an older brain, he said.

Dan Siegel, clinical professor of psychiatry at the UCLA School of Medicine, noted that many individuals experience post-traumatic growth after a stressful experience. “The researchers need to be commended for the hard work to get that data,” Siegel said. “You want to ask the larger question, of how is the brain remodeling process being affected?”

“This is a useful initial study,” agreed David Fassler, clinical professor of psychiatry at the University of Vermont. “I expect the results will inform the design of future research initiatives.”

In the paper, the authors acknowledge that they don’t know yet whether the physical changes to the brain will persist. They plan to take another set of scans at the next scheduled two-year point and continue to gather data about the study participants.

Stacy Gittleman, 54, of West Bloomfield, Mich., saw the pandemic derail one of her children. An aspiring musical theater actor, he was a junior in high school when school and theater shut down. “So much of how my son thrives depends on moving, acting, doing hands-on work and interacting with others,” Gittleman said. “He spent much of his time in bed, which was very painful as parents to watch, as my son before the pandemic was so lively and social.”

Managing his mental health will be a lifelong task, she said, noting that his older siblings, now 24 and 26, didn’t feel as much of an impact. “In the long term, the adversity thrown at the feet of our teenagers I believe will make them stronger and more resilient,” she said.

Other parents aren’t so sure. Meg Martin, 55, of Gaithersburg, Md., believes it’s too soon to tell whether teenagers will get back on track. Her son, now a senior in high school, previously intended to apply to a four-year residential college, but after years of online and hybrid learning, feels unmotivated and disengaged from school.

“I really think the way his high school years unfolded are going to have ripple effects for years to come,” Martin said.

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