A five-year study of 10,000 adolescents found that the pandemic damaged every teenager’s mental health, then hit the most genetically vulnerable ones with additional harm on top
When the pandemic ended and schools reopened, a widespread assumption took hold: the mental health crisis among teenagers was a product of the crisis conditions, and as those conditions lifted, the damage would gradually reverse. Time, normalcy, and the resilience of youth would do what they have always done. The children who struggled would recover. The rates would come back down.
Five years of data from 10,374 adolescents suggest the picture is considerably more complicated than that. A study published in Translational Psychiatry, drawing on the largest ongoing longitudinal study of adolescent brain development in the United States, has found that the pandemic’s effect on teenage mental health was not a single event that could simply be recovered from. It operated on two separate levels simultaneously, and understanding both is essential to understanding why so many young people have not bounced back the way the assumption predicted.
Two independent forces, not one
The Adolescent Brain Cognitive Development Study, known as ABCD, has been following the same group of American children since they were nine and ten years old, collecting detailed measures of brain development, mental health, and genetic information across five separate waves of data collection. The timing of the study meant that it captured the same children both before and during the COVID-19 pandemic, creating a rare natural experiment: researchers could track what happened to each child’s mental health as the pandemic arrived, with full knowledge of what that child’s mental health looked like before.
The research team, led by Chun Chieh Fan of the Laureate Institute for Brain Research, began by identifying genetic vulnerability. Using a technique called genomic structural equation modeling, they grouped the genetic liability for eight major psychiatric disorders into four underlying factors: a Compulsive factor covering OCD and anorexia, a Psychotic factor covering schizophrenia and bipolar disorder, a Neurodevelopmental factor covering ADHD and autism spectrum disorder, and an Internalizing factor covering depression and anxiety. They then computed polygenic risk scores for each child based on these four genetic factors.
The central question was whether the pandemic’s damage to adolescent mental health was driven primarily by genetics, by the environmental shock of the pandemic itself, or by some interaction between the two.
The answer was all three, but in a specific pattern that has important practical implications.
What the pandemic did to every teenager
Across the full cohort, the pandemic period was associated with significant increases in multiple mental health outcomes regardless of genetic risk. Parent-reported withdrawn and depressed behavior increased. Rule-breaking and conduct problems increased. Somatic complaints, ADHD symptoms, and aggressive behavior all moved upward. And across every mental health outcome that adolescents reported about themselves, scores worsened during the pandemic period.
This was not a story about genetically vulnerable children carrying the entire burden of the mental health crisis. The pandemic damaged the mental health of teenagers broadly, across the genetic risk spectrum. Children with low genetic vulnerability showed meaningful increases in psychological distress during the pandemic period. The environmental shock was real and it was wide.
“Pandemic periods were linked to significant increases in parent-reported withdrawn and depressed, rule-breaking, conduct, somatic, and ADHD symptoms, and in all youth-reported symptom scores, even after adjusting for genetic risk,” the researchers write.
What genetic risk added on top
The second layer of the finding is where the implications become more urgent. Among adolescents with higher polygenic risk scores for neurodevelopmental and internalizing psychiatric conditions, the pandemic did not simply replicate what it did to lower-risk children. It produced additional harm, on top of the elevated baseline these children already carried.
Each one standard deviation increase in neurodevelopmental or internalizing genetic risk was associated with a 3 to 21 percent increase in most psychopathology outcomes, depending on the specific symptom domain. And critically, the pandemic period interacted with these genetic risk scores: high-risk children showed greater increases during the pandemic than their genetic risk alone would have predicted. The pandemic and genetics were not simply adding their effects independently. In specific domains and for specific groups, the pandemic appeared to amplify what genetic vulnerability was already doing.
This pattern, in which an environmental stressor produces greater harm in individuals with pre-existing genetic susceptibility, is familiar from other areas of psychiatric research. It is one of the central ideas behind the stress-diathesis model: the same environmental pressure produces different outcomes depending on the biological substrate it encounters. What this study adds is a specific, well-powered demonstration of that principle in the context of one of the largest environmental stressors a generation of young people has ever faced.
Girls carried a heavier burden than boys
One of the study’s most concrete and clinically actionable findings concerns the difference between female and male adolescents. When the researchers stratified the analysis by sex, a clear pattern emerged.
Among female adolescents, parent-reported affective problems increased by 25 percent during the early pandemic period, with a 95 percent confidence interval of 16 to 34 percent. That is a substantial increase, and it was significantly larger than the corresponding increase seen in male adolescents. Girls with higher internalizing genetic risk also showed stronger associations between their genetic liability and symptom increases than boys with comparable genetic risk.
The interaction between genetics and the pandemic was most specifically concentrated in girls with higher neurodevelopmental polygenic risk scores. In this group, conduct problems increased by 16 percent during the early pandemic period beyond what would have been expected from their genetic risk alone. Aggressive behavior increased by 9 percent on the same basis. Both of these findings reached levels of statistical significance that make chance explanations unlikely.
This pattern is consistent with prior research showing that adolescent girls experienced steeper mental health deterioration during the pandemic than boys, and that the mechanisms underlying that deterioration involved both the social disruptions the pandemic produced, the loss of peer relationships, the collapse of school-based social structures, the shift to screen-based interaction, and the amplification of pre-existing vulnerabilities that those disruptions triggered.
Why the effects stacked rather than displaced each other
One of the more theoretically significant aspects of the findings is what did not happen. In some models of stress and vulnerability, environments and genetics compete: a strong environmental stressor can overwhelm genetic differences, producing similar outcomes across the risk spectrum, while a benign environment allows genetic differences to express themselves more fully. Under this model, the pandemic might have been so uniformly damaging that it flattened the differences between high and low genetic risk children, with everyone struggling equally.
The ABCD data did not support that picture. Genetic risk and pandemic exposure contributed independently to adolescent psychopathology, and in some domains they interacted. Higher-risk children did not simply fare the same as lower-risk children during the pandemic. They fared worse, in specific ways that tracked their specific genetic vulnerabilities, with the pandemic appearing to amplify rather than mask what was already present.
“Overall, genetic liability and pandemic period were independently associated with adolescent psychopathology, with pandemic-related increases occurring on top of elevated symptom burden among youth with higher polygenic risk scores,” the authors write.
What this means for the years ahead
The practical implications of the finding are significant for families, schools, and mental health systems that are still dealing with a generation of young people whose mental health was reshaped by the pandemic.
If the damage operated on two levels, recovery may also need to operate on two levels. General mental health support for adolescents, addressing the broad pandemic-related increases that affected all teenagers, is necessary but not sufficient. For children who carry higher genetic liability for neurodevelopmental or internalizing psychiatric conditions, the research suggests they may be carrying a heavier and more specific burden that requires targeted rather than generic support.
The identification of the four genetic factors, Compulsive, Psychotic, Neurodevelopmental, and Internalizing, as the relevant vulnerability dimensions provides a more specific framework for thinking about who is most at risk and for which outcomes. Adolescents with elevated neurodevelopmental genetic risk who showed the largest pandemic-period increases in conduct and aggressive behavior are not simply struggling for unexplained reasons. The study provides a biological and environmental framework for understanding why.
The limitation the researchers emphasize most directly is the restriction of the polygenic risk score findings to adolescents of European ancestry, a consequence of the current state of polygenic score methodology, which performs substantially less well across groups not well-represented in the genome-wide association studies on which the scores are based. The pandemic’s broader mental health effects, not dependent on genetic risk scores, were observed across the full cohort. But the specific genetic vulnerability findings cannot yet be generalized.
The five-year span of data the ABCD study has accumulated is one of the most detailed pictures of adolescent mental health development ever assembled. What it shows about the pandemic is not a temporary disruption that age and resilience will correct. It is a specific, quantifiable increase in psychological burden, larger in some children than others for identifiable genetic reasons, that will require specific, sustained attention to address.
Source
Lucy Shao, Jonathan Ahern, Robert Loughnan, Bohan Xu, Holly E. Baker, Susan F. Tapert, Fiona C. Baker, Wesley K. Thompson, Orsolya Kiss, Eva M. Müller-Oehring, Marie Gombert-Labedens, Chun Chieh Fan. “Contributions of genetic liability and the COVID-19 pandemic to rising psychopathology among youth in the United States.” Translational Psychiatry, July 15, 2026.
DOI: 10.1038/s41398-026-04184-2
