Publication date: Jul 15, 2026
Adolescent mental health concerns surged during the COVID-19 pandemic, but whether the pandemic amplified pre-existing genetic vulnerabilities remains unclear. This study examined how shared genetic liability for eight psychiatric disorders interacted with adolescent mental health during the pandemic. Using genomic structural equation modeling, we identified four latent genetic factors: Compulsive, Psychotic, Neurodevelopmental, and Internalizing. We computed corresponding polygenic risk scores (PRS) in 10,374 participants from the Adolescent Brain Cognitive Development (ABCD) Study(c) across five waves and modeled on 20 psychopathology outcomes using longitudinal mixed models, stratified by sex and ancestry. Among European-ancestry adolescents, each 1 standard deviation increase in neurodevelopmental or internal PRS was associated with a 3-21% increase in most psychopathologies. Pandemic periods were linked to significant increases in parent-reported withdrawn/depressed, rule-breaking, conduct, somatic, and ADHD symptoms, and in all youth-reported symptom scores, even after adjusting for PRS. In sex-stratified analyses, females showed a greater increase in parent reported affective problems during the early pandemic (25% increase; 95% CI: 16-34%) and stronger associations between internal PRS and symptom increases than males. Interactions between neurodevelopmental PRS and the early pandemic period were observed for conduct (16%; 95% CI 9-25%; P = 1. 2 cD7 10⁻⁵) and aggressive behavior (9%; 95% CI 4-15%; P = 6. 8 cD7 10⁻⁴) scores in females. 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 PRS. These findings highlight the need for targeted mental health support during widespread stressors, especially for genetically at-risk adolescents.
Open Access PDF
| Concepts | Keywords |
|---|---|
| Adolescent | |
| Covid | |
| Genetic | |
| Increase | |
| Increases | |
| Liability | |
| Mental | |
| Neurodevelopmental | |
| Pandemic | |
| Prs | |
| Psychopathology | |
| Reported | |
| Scores | |
| Symptom | |
| Youth |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 pandemic |
| disease | MESH | psychiatric disorders |
| disease | MESH | polygenic risk scores |
| disease | MESH | PRS |
| disease | MESH | ADHD |
| pathway | REACTOME | Reproduction |
| disease | MESH | included |
| disease | MESH | Park |
| disease | MESH | anxiety |
| disease | MESH | infection |
| disease | MESH | strain |
| disease | MESH | syndrome |
| disease | MESH | depressive disorders |
| drug | DRUGBANK | Medical air |
| disease | MESH | anorexia nervosa |
| disease | MESH | autism spectrum disorder |
| disease | MESH | bipolar disorder |
| disease | MESH | major Depressive disorder |
| disease | MESH | obsessive compulsive disorder |
| disease | MESH | schizophrenia |
| drug | DRUGBANK | Coenzyme M |
| disease | MESH | Psychotic disorders |
| disease | MESH | Neurodevelopmental disorders |
| drug | DRUGBANK | Pentaerythritol tetranitrate |
| disease | MESH | PCs |
| disease | MESH | Pandemic*ND |
| disease | MESH | genetic predispositions |
| disease | MESH | long COVID |
| disease | MESH | autism |