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A new study published in Translational Psychiatry has found that adolescents who experienced the COVID-19 pandemic and associated lockdowns show significant differences in stress-related biological systems compared to their peers assessed before the pandemic. The new findings suggest that pandemic-related disruptions may have lasting effects on adolescent development at multiple biological levels.
The COVID-19 pandemic was an acute and prolonged stressor that dramatically altered daily life. While earlier research had shown sharp increases in adolescent anxiety and depression during the pandemic, much less was known about how this stress affected neurobiological development.
“Adolescence is a critical time developmental period, shaping who youth become as adults,” said study author Justin Ping Yuan, a postdoctoral Health Science Fellow at the San Francisco Veterans Affairs Medical Center who conducted the research while a PhD student working with Ian Gotlib in the Stanford Neurodevelopment, Affect, and Psychopathology Lab.
For an entire generation this period was disrupted by the COVID-19 pandemic and associated lockdowns. We knew that these experiences adversely affected teens’ mental health, but it wasn’t clear whether they also had an impact on their bodies and brains. That is what drove us to explore this topic,”
Previous studies have shown that early life stress can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, increase inflammation, and alter brain development—effects that raise long-term risks for poor mental and physical health. In this context, the researchers aimed to investigate whether the COVID-19 pandemic had measurable effects on these same biological systems.
They focused on three stress-sensitive domains: the HPA axis (which regulates cortisol, the body’s primary stress hormone), systemic inflammation (measured via C-reactive protein or CRP), and neural responses to emotionally meaningful stimuli. By comparing adolescents assessed before the pandemic to those assessed after lockdown restrictions ended, the researchers hoped to identify how the experience of the pandemic shaped the biological underpinnings of adolescent stress response.
The study drew from an ongoing longitudinal project at Stanford University that began in 2013. The researchers selected 154 adolescents from the larger cohort, matching 76 participants who were assessed before the pandemic (from 2016 to 2019) with 78 who were assessed after the lockdowns (from October 2020 to March 2022). The groups were matched by age and sex, and did not differ significantly in early life stress, socioeconomic status, race, or pubertal development. Only one participant in the post-lockdown group had contracted COVID-19, allowing the researchers to isolate the effects of the lockdown experience rather than infection itself.
To assess stress physiology, participants provided saliva samples four times per day across two days. These samples were used to calculate total daily cortisol output, as well as the cortisol awakening response (CAR), which reflects the sharp increase in cortisol shortly after waking. Systemic inflammation was assessed via dried blood spots analyzed for CRP levels. Brain function was measured using fMRI while participants completed two tasks: a monetary incentive task that probes reward processing, and an affect labeling task that taps into implicit emotion regulation.
Across all three biological systems, adolescents assessed after the pandemic differed from those assessed before. First, the post-pandemic group showed lower total cortisol production throughout the day. This pattern—reduced area under the curve for cortisol—suggests a dampened HPA axis response, which has previously been associated with chronic stress and prolonged exposure to adversity. There was no difference between the groups in the cortisol awakening response, indicating that specific aspects of cortisol regulation may have been more affected than others.
Second, adolescents in the post-lockdown group had higher levels of CRP, a marker of systemic inflammation. While elevated inflammation is expected in individuals with infection or chronic illness, this finding suggests a stress-related shift toward a pro-inflammatory state in otherwise healthy teens. These immune changes are especially concerning given evidence linking chronic inflammation with increased risk for depression, cardiovascular problems, and other health issues later in life.
Third, the researchers found notable differences in brain activity during the two tasks. Adolescents who had lived through the lockdowns showed reduced activation in the medial prefrontal cortex when receiving monetary rewards, and in the ventrolateral prefrontal cortex when labeling emotional faces. These regions play central roles in motivation, decision-making, and emotional control.
The results suggest that adolescents may have become less responsive to reward and less effective at regulating emotions after experiencing pandemic-related stress. Interestingly, the groups did not differ in activity within the nucleus accumbens, another brain region involved in reward anticipation, suggesting that the effects were specific to certain aspects of the reward and regulation processes.
“Our findings indicate that teens went through a profoundly stressful period during the pandemic, and it appears to have adversely affected their biological functioning, including the development of their brain, HPA axis, and immune systems,” Yuan told PsyPost. “We were surprised by how much the teens who experienced the COVID-19 lockdowns looked biologically like people who have been exposed to significant early life stress or trauma. These traumatic experiences (also referred to as adverse childhood experiences, or ACEs) can have a lasting impact on the body and brain. It was striking to us that youth who experienced the pandemic lockdowns, which spanned a relatively short timeframe, had similar patterns of biological functioning as people exposed to early life stress.”
But as with all research, there are some limitations. The analyses were exploratory and not pre-registered, as the study was not originally designed to test the effects of a global pandemic. Although they used multiple imputation to account for missing data and found consistent results across sensitivity analyses, the sample size was relatively small for a neuroimaging study.
Larger samples will be needed to replicate these findings and examine long-term outcomes. Additionally, the sample was predominantly white and from higher-income households. Adolescents from more disadvantaged backgrounds or marginalized communities may have experienced even greater disruptions during the pandemic, so future research should explore whether similar or more severe biological effects occurred in those groups.
Long-term follow-up will be essential. The authors suggest that the pandemic may have altered the developmental trajectory of today’s adolescents in ways that are not yet fully understood.
“Broadly, these findings suggest that the pandemic and lockdowns changed the course of adolescents’ psychobiological development,” Yuan explained. “It will be important for researchers to understand what this ‘new normal’ might look like longer-term and whether there continue to be adverse effects of the pandemic even now so that we best support youth post-pandemic.”
“A common question we are asked is if these differences are due to COVID infection itself. Only a very small number of the adolescents in our project were actually infected with the COVID-19 virus, but all had experienced the lockdowns. This means that the difficulties in their functioning are not explained by the virus itself, but rather, by having experienced the pandemic and its lockdowns.”
“We also want to express our deep gratitude to our participants and their families,” Yuan added. “Many of them came to in-person sessions during the pandemic to provide blood samples and participate in brain scans, making this research possible.”
The study, “The effects of the COVID-19 pandemic on neurobiological functioning in adolescents,” was authored by Justin P. Yuan, Lauren R. Borchers, Yoonji Lee, Jessica L. Buthmann, Saché M. Coury, Julian Joachimsthaler, Emma L. Jaeger, Tiffany C. Ho, and Ian H. Gotlib.
