Yoonji Lee

All Publications

• Neural Efficiency as a Brain-Wide Signature of Pediatric Anxiety and a Biomarker for Treatment Response. The American journal of psychiatry Gotlib, I. H., Lee, Y. 2026; 183 (1): 7-9

  View details for DOI 10.1176/appi.ajp.20251091

  View details for PubMedID 41476334

• Task-Rest Reconfiguration Efficiency of the Reward Network Across Adolescence and its Association With Early Life Stress and Depressive Symptoms. Journal of the American Academy of Child and Adolescent Psychiatry Lee, Y., Yuan, J. P., Winkler, A. M., Kircanski, K., Pine, D. S., Gotlib, I. H. 2024

  Abstract

  Adolescents face significant changes in many domains of their daily lives that require them to flexibly adapt to changing environmental demands. To shift efficiently among various goals, adolescents must reconfigure their brains, disengaging from previous tasks and engaging in new activities.To examine this reconfiguration, we obtained resting-state and task-based fMRI scans in a community sample of 164 adolescents. We assessed the similarity of functional connectivity (FC) of the reward network between resting state and a reward processing state, indexing the degree of reward network reconfiguration required to meet task demands. Given research documenting relations among reward network function, early life stress (ELS), and adolescent depression, we examined the association of reconfiguration efficiency with age across adolescence, the moderating effect of ELS on this association, and the relation between reconfiguration efficiency and depressive symptoms.We found that older adolescents showed greater reconfiguration efficiency than younger adolescents and, further, that this age-related association was moderated by the experience of ELS.These findings suggest that reconfiguration efficiency of the reward network increases over adolescence, a developmental pattern that is attenuated in adolescents exposed to severe ELS. In addition, even after controlling for the effects of age and exposure to ELS, adolescents with higher levels of depressive symptoms exhibited greater reconfiguration efficiency, suggesting that they have brain states at rest that are more strongly optimized for reward processing than do asymptomatic youth.

  View details for DOI 10.1016/j.jaac.2024.04.018

  View details for PubMedID 38878818

• The cortisol/DHEA ratio mediates the association between early life stress and externalizing problems in adolescent boys. Psychoneuroendocrinology Lee, Y., Donahue, G. Z., Buthmann, J. L., Uy, J. P., Gotlib, I. H. 2024; 165: 107034

  Abstract

  Despite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations.138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems.We found that ELS is associated with both a lower CD ratio and more externalizing problems. Importantly, a lower CD ratio mediated the association between ELS and externalizing problems in boys.An imbalance in adrenal hormones may be a mechanism through which ELS leads to an increase in externalizing problems in adolescent boys. These findings underscore the utility of using the CD ratio to index HPA-axis functioning.

  View details for DOI 10.1016/j.psyneuen.2024.107034

  View details for PubMedID 38554595

• The default mode network is associated with changes in internalizing and externalizing problems differently in adolescent boys and girls. Development and psychopathology Lee, Y., Chahal, R., Gotlib, I. H. 2023: 1-10

  Abstract

  Internalizing and externalizing problems that emerge during adolescence differentially increase boys' and girls' risk for developing psychiatric disorders. It is not clear, however, whether there are sex differences in the intrinsic functional architecture of the brain that underlie changes in the severity of internalizing and externalizing problems in adolescents. Using resting-state fMRI data and self-reports of behavioral problems obtained from 128 adolescents (73 females; 9-14 years old) at two timepoints, we conducted multivoxel pattern analysis to identify resting-state functional connectivity markers at baseline that predict changes in the severity of internalizing and externalizing problems in boys and girls 2 years later. We found sex-differentiated involvement of the default mode network in changes in internalizing and externalizing problems. Whereas changes in internalizing problems were associated with the dorsal medial subsystem in boys and with the medial temporal subsystem in girls, changes in externalizing problems were predicted by hyperconnectivity between core nodes of the DMN and frontoparietal network in boys and hypoconnectivity between the DMN and affective networks in girls. Our results suggest that different neural mechanisms predict changes in internalizing and externalizing problems in adolescent boys and girls and offer insights concerning mechanisms that underlie sex differences in the expression of psychopathology in adolescence.

  View details for DOI 10.1017/S0954579423000111

  View details for PubMedID 36847268

• Inflammation, fronto-amygdala connectivity, and negative affective reactivity to daily stress in adolescents. Brain, behavior, & immunity - health Giampetruzzi, E., Yuan, J. P., Uy, J. P., Antonacci, C., Lee, Y., Gotlib, I. H. 2026; 55: 101280

  Abstract

  Maladaptive affective responses to daily stress in adolescence are a robust risk factor for the development of psychopathology. Importantly, however, adolescents vary widely in the magnitude of their affective reactivity to stress. Although peripheral inflammation and fronto-amygdala circuitry during emotion regulation are both plausible biological contributors to this variability, no study has yet integrated inflammatory markers, neural metrics of emotion regulation, and real-world assessments of stress and affect to examine how these systems interact to shape affective reactivity to stress in adolescents' daily life.Adolescents (N = 124; 60% female) aged 13.07-20.10 years (M = 16.20) completed a 14-day ecological momentary assessment (EMA) protocol assessing stressor occurrence, stress severity, and momentary affect. A subset of participants provided peripheral blood samples assayed for C-reactive protein (CRP) to index systemic inflammation (N = 85), and a further subset completed an fMRI affect-labeling task to quantify task-related functional connectivity between the amygdala and lateral prefrontal cortex (LPFC; N = 68). Multilevel models tested whether higher CRP predicted stronger within-person coupling of stress and negative affect (NA), and whether LPFC-amygdala connectivity moderated this association.Higher stress severity predicted higher NA, and greater inflammation potentiated these stress-related increases in NA. A three-way interaction with DLPFC-amygdala connectivity may further moderate this association, but the effect did not survive correction for multiple comparisons, and the sample was underpowered to test it reliably.Inflammation was linked to stronger coupling of daily stress and negative affect in adolescents. Whether fronto-amygdala connectivity adds to this remains untested at adequate power.

  View details for DOI 10.1016/j.bbih.2026.101280

  View details for PubMedID 42294081

  View details for PubMedCentralID PMC13254783

• Stress Sensitivity in Early Life Moderates the Association Between Salience and Default Mode Network Resting-State Functional Connectivity and Anxiety Symptoms in Young Adulthood Bahk, J., Lee, Y., Gotlib, I. H. ELSEVIER SCIENCE INC. 2026

  View details for Web of Science ID 001765464500129

• Frontolimbic Connectivity and Threat-Related Psychopathology: A Data-Driven Test of Models of Early Adversity. Developmental psychobiology Antonacci, C., Buthmann, J. L., Uy, J. P., Khosravi, P., Lee, Y., Gotlib, I. H. 2025; 67 (5): e70080

  Abstract

  Early adversity is a well-established risk factor for psychopathology in youth. Contemporary taxonomies of adversity seek to distill the diverse stressors children face into meaningful categories of experience to enable more precise prediction of risk; however, few studies have tested these models using data-driven approaches in well-characterized, longitudinal samples. Here, we examined the latent structure of early stress across diverse domains of exposure, tested differential associations with psychopathology in adolescence, and investigated frontolimbic functional connectivity as a potential mediator. In a sample of 168 youth (Mage = 11.36), factor analyses identified two latent stress factors at baseline-"Parenting" and "Deprivation & Unpredictability"-and a single "Psychopathology" factor extracted from measures of mental health obtained 2 years later. While adverse parenting predicted greater psychopathology, exposure to threat emerged as the strongest predictor of adolescent mental health problems. High-dimensional regularized mediation analyses revealed that frontolimbic functional connectivity mediated the association between Threat and Psychopathology in girls but not in boys. These findings suggest that widely used dimensional models overlook key aspects of adversity, including sex-linked asymmetries across neurodevelopment and the distinct role of parenting-related stress. Refining adversity taxonomies across diverse samples and stress domains is crucial to advancing targeted interventions for youth mental health.

  View details for DOI 10.1002/dev.70080

  View details for PubMedID 40898734

• Pollution burden and trajectories of pubertal development: Implications for sleep disturbances and depressive symptoms. Psychoneuroendocrinology Uy, J. P., Shenoy, T. N., Lee, Y., Buthmann, J. L., Gotlib, I. H. 2025; 181: 107586

  Abstract

  Childhood exposure to pollution has been associated with elevated levels of depressive symptoms during adolescence. Epidemiological studies have related exposure to pollution to altered pubertal timing; however, the effects of pollution exposure on levels of pubertal hormones and their developmental trajectories (i.e., pubertal tempo) are not known. Furthermore, how pollution-related alterations in pubertal development influence trajectories of depressive symptoms during adolescence is not well understood. One factor that has been linked to pollution exposure, pubertal development, and depressive symptoms, and that is modifiable, is sleep disturbances; these variables, however, have not been examined together in a single investigation. The current study examined the effects of pollution burden during childhood on trajectories of adrenal and gonadal development and their impact on trajectories of sleep disturbances and depressive symptoms during adolescence. 184 adolescents (109 females) completed four assessments, each approximately 2 years apart, starting at 9-13 years of age (M=11.37, SD=1.06). At each timepoint, participants completed measures assessing pubertal development, sleep disturbances, and depressive symptoms and provided saliva samples, from which levels of DHEA, testosterone, and estradiol (females only) were assayed. We estimated participants' pollution burden at the census tract-level using their residential addresses and publicly available environmental data. We found that female adolescents residing in neighborhoods with greater pollution burden showed delayed adrenarche and gonadarche based on levels of DHEA and estradiol, respectively, followed by faster DHEA and estradiol tempo into middle adolescence. These pollution burden-related increases in DHEA and estradiol tempo interacted with increasing levels of sleep disturbances to predict the highest increase in levels of depressive symptoms. Although pollution burden was associated with altered adrenal development in male adolescents, effects differed for DHEA and self-reported development, and these alterations did not interact with increases in sleep disturbances to predict trajectories of depressive symptoms. Thus, childhood pollution burden appears to affect pubertal development in sex-dependent ways that contribute to sex-differentiated risk for depression in adolescence.

  View details for DOI 10.1016/j.psyneuen.2025.107586

  View details for PubMedID 40907146

• The effects of the COVID-19 pandemic on neurobiological functioning in adolescents. Translational psychiatry Yuan, J. P., Borchers, L. R., Lee, Y., Buthmann, J. L., Coury, S. M., Joachimsthaler, J., Jaeger, E. L., Ho, T. C., Gotlib, I. H. 2025; 15 (1): 276

  Abstract

  The COVID-19 pandemic and its associated lockdowns were an unprecedented source of stress, with striking adverse effects on adolescents' mental health but relatively unknown effects on important aspects of neurobiological functioning. Using data from 154 adolescents (age M ± SD = 16.2 ± 1.1 years; range = 13.9-19.4) drawn from an ongoing longitudinal study and assessed either before or after the pandemic, we compared the pre-pandemic and post-pandemic groups on three key stress-sensitive biological systems: the hypothalamic-pituitary-adrenal (HPA) axis, immune response, and neural responses to affective stimuli. We found that compared to those assessed before the pandemic, adolescents assessed post-lockdown had significantly lower total cortisol production, elevated levels of systemic inflammation, and reduced neural activation in the prefrontal cortex during affective processing (pseudo-F(1,3250) = 7.43, p = 0.006). These findings suggest that, for adolescents, the experience of the pandemic was associated with significant disruptions in multiple biological systems that are sensitive to stress that might have enduring adverse developmental effects.

  View details for DOI 10.1038/s41398-025-03485-2

  View details for PubMedID 40796772

  View details for PubMedCentralID 10706127