All Publications


  • 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

  • In Utero PFAS Exposure, Inflammation, and Behavioral Problems in Childhood. Environmental research Rocha, S., Buthmann, J. L., Antonacci, C., Uy, J. P., Tan, A. P., Chong, Y. S., Chen, H., Eriksson, J., Gotlib, I. H. 2026: 125260

    Abstract

    Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been posited to be harmful for neurodevelopment; however, researchers have not yet examined its influence on behavioral problems longitudinally across childhood or the immunological underpinnings of these links.This birth-cohort study followed 264 Singaporean mother-infant dyads from the prenatal period to 10.5 years post-delivery. Concentrations of 9 PFAS and 3 inflammatory markers were assayed from umbilical cord blood. Internalizing and externalizing problems were assessed using the Child Behavior Checklist when children were ages 2, 3, 4, 7, and 10.5 years. Linear mixed effect models estimated the associations of PFAS with children's internalizing and externalizing problems as children aged. For the PFAS that were significantly associated with children's behavioral problems, we tested whether levels of inflammatory cytokines statistically mediated the associations.Higher cord blood concentrations of PFNA, PFDA and PFUnDA were associated with more severe internalizing problems at 2 years of age (PFNA: B = 1.65 [0.60, 2.71]; PFDA: B = 1.85 [0.81, 2.89]; PFUnDA: B = 1.26 [0.27, 2.25]). Two of these associations (PFNA, PFDA) weakened significantly as children aged (PFNA: B = -0.26 [-0.44, -0.08]; PFDA: B = -0.35 [-0.52, -0.17]). Higher levels of cord blood interleukin (IL)-6 mediated the association of PFNA with internalizing problems (B = 0.25 [0.01, 0.58]).Greater in utero exposure to three types of PFAS was related to more severe internalizing problems from two to four years of age, with associations attenuated after 7 years of age. Inflammation may be one pathway through which PFAS influence development, although replication is warranted.

    View details for DOI 10.1016/j.envres.2026.125260

    View details for PubMedID 42457111

  • Developmental stability of task-rest neural efficiency in youth using a threat and cognitive control task FRONTIERS IN HUMAN NEUROSCIENCE Khosravi, P., Linke, J. O., Poe, A. D., Antonacci, C., Naim, R., Cardinale, E., Kircanski, K., Winkler, A., Fox, N., Pine, D. S., Haller, S. P. 2026; 20
  • Developmental stability of task-rest neural efficiency in youth using a threat and cognitive control task. Frontiers in human neuroscience Khosravi, P., Linke, J. O., Poe, A. D., Antonacci, C., Naim, R., Cardinale, E., Kircanski, K., Winkler, A., Fox, N., Pine, D. S., Haller, S. P. 2026; 20: 1839961

    Abstract

    Behaviors arise from coordinated neural activity across diverse spatial and temporal scales. Prior work has linked better task performance and cognitive functioning to patterns of global network connectivity requiring minimal reconfiguration when switching between task demands. This metric indexing similarity in functional connectivity across task and rest has been termed "neural efficiency." Here we assess stability of neural efficiency over approximately 3 years in adolescence, specificity across two task-rest combinations and associations with anxiety. At approximately age 16 and/or 19, 95 participants completed a resting state scan alongside a cognitive control and/or threat task. Neural efficiency was quantified as partial correlations between intrinsic and task-related functional connectivity patterns across the whole brain. We tested temporal stability across the three-year interval, as well as associations with task performance and anxiety across the two task-rest combinations at the two time points. Neural efficiency values remained relatively stable from mid to late adolescence (ICC[3,1] = 0.51-0.58). The cognitive control task showed higher values than the threat task. Across tasks, neural efficiency was associated with better performance (i.e., reduced interference), although not consistently (r = -0.19, p = 0.26 - r = -0.37, p = 0.021). These effects did not survive correction for multiple testing. No associations were found between neural efficiency and self/parent-reported anxiety. In sum, the metric shows moderate developmental stability and associations with task performance. Task features impact neural efficiency. Given small sample sizes, findings need to be interpreted cautiously.

    View details for DOI 10.3389/fnhum.2026.1839961

    View details for PubMedID 42518775

    View details for PubMedCentralID PMC13381436

  • The promise of digital phenotyping for the early detection of risk for depression in adolescents NATURE MENTAL HEALTH Giampetruzzi, E., Antonacci, C., Gotlib, I. H. 2026
  • Trajectories of internalizing problems during and after the COVID-19 pandemic: The effects of sex and early life stress. Journal of affective disorders Buthmann, J. L., Uy, J. P., Rocha, S. E., Antonacci, C. A., Gotlib, I. H. 2026; 412: 122089

    Abstract

    The COVID-19 pandemic and its associated lockdowns had a detrimental impact on adolescent mental health, exacerbating levels of emotional difficulties that were already increasing in this population. The course of these difficulties after lockdown protocols ended, however, is not fully understood. Further, the effects of early life stress (ELS) and biological sex on mental health during and following the pandemic are also not clear. This study leverages data from a longitudinal project examining adolescent mental health that predates the pandemic. Internalizing problems were assessed in 222 children (58.6% females) ages 9-13 years at recruitment (baseline; 2013-2016) and at four more timepoints, each approximately two years apart. Participants also completed an interview assessing ELS at baseline. We assessed internalizing problems across each phase of the pandemic (i.e., pre-COVID, during the COVID lockdown, after reopening) as a function of ELS and biological sex. We found that whereas unpredictability-related ELS was associated with internalizing problems in girls across all COVID phases, the association between threat-related ELS and internalizing problems from pre-lockdown to post-reopening decreased in girls and increased in boys. Further, threat-related ELS was associated with post-reopening internalizing problems in boys through lower adaptability. Sensitivity analysis showed that the attenuation of the threat-internalizing association in girls and strengthening of the association in boys was not due to aging. Collectively, these findings suggest that there are sex- and ELS-specific changes in psychological functioning in relation to the pandemic. Further research is needed to better understand mechanisms that foster risk or resilience following stress exposure.

    View details for DOI 10.1016/j.jad.2026.122089

    View details for PubMedID 42250611

  • Continuous Versus Grouping Approaches to Resilience: Predicting Mental Health Following Adversity in Two Longitudinal Datasets. JAACAP open Borchers, L. R., Antonacci, C., Copeland, W. E., Meaney, M. J., Gotlib, I. H. 2026; 4 (3): 442-453

    Abstract

    Resilience in psychiatry is often defined as the absence of psychopathology following early adversity. Resilience may be better operationalized as a continuous construct reflecting the degree to which individuals are functioning better than would be predicted given their adversity exposure. We used a continuous metric of resilience to predict mental health problems in 2 richly phenotyped samples studied longitudinally, and compared findings to those of conventional grouping approaches.Exposure to early adversity was assessed at baseline (Study I: N = 1,265; Study II: N = 191), and mental health was assessed several times over a decade (9-21 years of age). Resilience was defined as the residual of participants' mental health symptoms accounting for early adversity. We then used generalized additive models to examine mental health symptoms across adolescence as a function of resilience to adversity. Finally, we compared continuous approaches with grouping approaches to assess resilience.In both studies, greater resilience to adversity in childhood predicted fewer mental health problems in adolescence. Although both approaches to modeling resilience predicted unique variance in subsequent mental health symptoms when modeled simultaneously, the grouping approaches identified fewer individuals as resilient than did the continuous approach.A continuous approach to operationalizing resilience significantly predicted mental health symptoms across adolescence. Furthermore, both continuous and categorical operationalizations predicted unique variance in mental health outcomes. Importantly, however, grouping approaches may overlook a significant number of individuals who are, by a continuous assessment, resilient. Determining the optimal approach for identifying resilient individuals should be a priority for mental health research.

    View details for DOI 10.1016/j.jaacop.2026.01.002

    View details for PubMedID 42220638

    View details for PubMedCentralID PMC13221814

  • Longitudinal development of the anterior insula-nucleus accumbens white matter pathway through adolescence predicts risk taking in young adulthood. Developmental cognitive neuroscience Borchers, L. R., Antonacci, C., Leong, J. K., Gotlib, I. H. 2026; 79: 101730

    Abstract

    Adolescence is characterized by increases in risk-taking behaviors, including substance use, sexual activity, and impulsive decision-making. Neuroimaging research implicates the anterior insula (AIns) and nucleus accumbens (NAcc) in risk evaluation and reward motivation; however, little is known about how the structural pathway connecting these regions develops across adolescence or whether variation in its development predicts later risk-taking. In this study, we examined whether longitudinal changes in white-matter connectivity between the AIns and NAcc during adolescence predict risk-taking in early adulthood. A total of 196 youth (ages 9-20 years) contributed 486 diffusion-weighted imaging scans across four waves spanning six years. We reconstructed the AIns-NAcc tract using probabilistic tractography and extracted fractional anisotropy (FA) along the tract. At a fifth assessment (ages 19-23), 105 participants completed the Adolescent and Young Adult Health Questionnaire; exploratory factor analysis identified a risk-taking factor indexing substance use and sexual risk-taking. We used linear mixed-effects models to characterize developmental trajectories of FA and tested their associations with early adult risk-taking, adjusting for biological sex, early life stress, and behavioral sensitivity to reward and punishment. FA increased linearly across adolescence in both hemispheres (right: β=0.17, p < .001; left: β=0.10, p = .023). Critically, individuals exhibiting shallower increases in FA across adolescence in the right hemisphere reported greater engagement in risk-taking behaviors in early adulthood (ΔR2=4.0%, p = .024). These findings suggest that adolescence represents a sensitive period during which individual differences in maturation of the right AIns-NAcc pathway prospectively shape later risk-taking, highlighting the importance of longitudinally modeling structural connectivity in reward-related circuits.

    View details for DOI 10.1016/j.dcn.2026.101730

    View details for PubMedID 42054974

  • Reward-network connectivity in childhood predicts multi-domain dysregulation in adolescence. Journal of child psychology and psychiatry, and allied disciplines Giampetruzzi, E., Khosravi, P., Kircanski, K., Antonacci, C., Pine, D. S., Gotlib, I. H. 2026

    Abstract

    Multi-domain dysregulation in adolescence, indexed by co-occurring affective, cognitive, and behavioural difficulties, is a robust transdiagnostic risk factor. However, its developmental course and neural antecedents are poorly understood. Given heightened emotional reactivity and impulsivity in adolescence, alterations in reward-network connectivity may represent an early neural marker of risk.Adolescents completed four assessments approximately two years apart between ages 9-13 and 15-18 years. Multi-domain dysregulation was assessed at each wave using the Youth Self-Report Dysregulation Profile (YSR-DP), computed as the sum of the anxious/depressed, aggressive behaviour, and attention problems subscales. Resting-state fMRI was acquired at baseline (Mage = 11.34 years). Piecewise linear mixed-effects models (N = 211) characterized trajectories of YSR-DP scores across adolescence. Principal component scores indexing a Latent Dysregulation Factor were used to derive residualised change in dysregulation, and regression analyses (N = 94) tested whether baseline reward-network connectivity predicted this change.YSR-DP scores declined from late childhood to early adolescence, increased from early to mid-adolescence, and then stabilized in late adolescence. Weaker connectivity within the reward network in late childhood predicted greater increases in the latent dysregulation factor from early to mid-adolescence, above and beyond baseline dysregulation. Connectivity in seven large-scale control networks did not predict changes in dysregulation.Multi-domain dysregulation follows a nonlinear trajectory across adolescence, and weaker reward-network connectivity in childhood prospectively predicts subsequent escalation of this phenotype. Prevention and intervention efforts may benefit from targeting reward processing and regulatory skills in late childhood and early adolescence.

    View details for DOI 10.1111/jcpp.70143

    View details for PubMedID 41774020

  • The effects of daily air pollution on affect in adolescents: An ecological momentary assessment study. Journal of affective disorders Rocha, S., Antonacci, C., Uy, J. P., Gotlib, I. H. 2026; 403: 121502

    Abstract

    Air pollution is a global threat to health and is particularly harmful to adolescents. To date, however, our understanding of the immediate effects of air pollution on adolescents' emotional functioning is limited. In this ecological momentary assessment study, we assessed daily levels of air quality across a two-week period in 158 adolescents (MAge = 16.1 years) in the San Francisco Bay Area. Adolescents reported on their levels of positive and negative affect and their experiences of stress three times per day, resulting in 4113 observations. We examined associations of daily levels of four major air pollutants (carbon monoxide [CO], nitrogen dioxide [NO2], ozone [O3], and particulate matter <2.5 μm [PM2.5]) with adolescents' same- and next-day ratings of the levels of their affect, the lability of their affect, and their affective reactivity to reported stressors. We found that on days with higher levels of NO2 and O3, adolescents reported lower levels of positive affect. On both the same and the following day, higher levels of O3 were associated with greater lability of positive affect, and higher levels of CO and PM2.5 were associated with greater lability of both positive and negative affect. Finally, on days with higher CO and PM2.5, as well as on the following day, adolescents reported having more negative affect after experiencing stressful situations. These findings elucidate the effects of different forms of air pollution on daily emotional functioning in adolescents and underscore the need to identify mechanistic pathways that might mediate these associations.

    View details for DOI 10.1016/j.jad.2026.121502

    View details for PubMedID 41740753

  • 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

  • Nucleus accumbens volume mediates the association between prenatal adversity and attention problems in youth. Development and psychopathology Antonacci, C., Buthmann, J. L., Borchers, L. R., Fortier, M. V., Chong, Y. S., Gluckman, P., Eriksson, J., Chen, H. Y., Law, E., Meaney, M. J., Tan, A. P., Gotlib, I. H. 2025: 1-13

    Abstract

    Exposure to adversity during the perinatal period has been associated with cognitive difficulties in children. Given the role of the nucleus accumbens (NAcc) in attention and impulsivity, we examined whether NAcc volume at age six mediates the relations between pre- and postnatal adversity and subsequent attention problems in offspring. 306 pregnant women were recruited as part of the Growing Up in Singapore Towards Healthy Outcomes Study. Psychosocial stress was assessed during pregnancy and across the first 5 years postpartum. At six years of age, children underwent structural MRI and, at age seven years, mothers reported on their children's attention problems. Separate factor analyses conducted on measures of pre- and postnatal adversity each yielded two latent factors: maternal mental health and socioeconomic status. Both pre- and postnatal maternal mental health predicted children's attention difficulties. Further, NAcc volume mediated the relation between prenatal, but not postnatal, maternal mental health and children's attention problems. These findings suggest that the NAcc is particularly vulnerable to prenatal maternal mental health challenges and contributes to offspring attention problems. Characterizing the temporal sensitivity of neurobiological structures to adversity will help to elucidate mechanisms linking environmental exposures and behavior, facilitating the development of neuroscience-informed interventions for childhood difficulties.

    View details for DOI 10.1017/S0954579425000240

    View details for PubMedID 40232121

  • Neighborhood opportunity and response to psychotherapy in anxious youth. Psychiatry research Antonacci, C., Zugman, A., Morales, I., Cardinale, E. M., Frank, S. E., Lewis, K. M., Berman, E., Gotlib, I. H., Pine, D. S. 2025; 348: 116484

    Abstract

    Early adversity is a well-documented risk factor for anxiety disorders in youth; few studies, however, have examined how exposure to adversity influences treatment outcomes. Emerging research suggests that systemic inequities can affect the efficacy of frontline psychotherapies. The effects of structural disadvantage and, in particular, neighborhood-level features on treatment outcomes for pediatric anxiety are largely under-studied. The current study aimed to examine the impact of neighborhood opportunity on children's response to cognitive behavioral therapy (CBT). A total of 202 youth aged 8-17 years (Mage = 12.030, 56 % F) with a diagnosed anxiety disorder completed 8-12 weeks of exposure-based CBT. Neighborhood disadvantage was quantified using the Child Opportunity Index (COI), and treatment response was measured via the Pediatric Anxiety Rating Scale (PARS) at baseline, post-treatment, and a 6-month follow-up assessment. Following treatment, anxious youth exhibited a significant 31.523 % reduction in symptoms. Across all scoring dimensions of the COI (socioeconomic, education, and health & environment), neighborhood disadvantage did not reliably predict treatment response. These findings suggest that when provided access to high-quality, evidence-based psychotherapy, youth from lower opportunity neighborhoods achieve comparable outcomes to their more advantaged peers. Taken together with prior research, this study suggests that structural disadvantage at the neighborhood level is not a robust predictor of treatment outcomes in the context of pediatric anxiety. These findings raise the possibility that equitable access to treatment could, in certain circumstances, mitigate the negative effects of systemic neighborhood-level inequities on mental health outcomes, underscoring the importance of expanding the availability of treatment services.

    View details for DOI 10.1016/j.psychres.2025.116484

    View details for PubMedID 40194352

  • Nucleus Accumbens Volume Mediates the Association Between Prenatal Adversity and Attention Problems in Youth Antonacci, C., Buthmann, J. L., Borchers, L., Tan, A., Meaney, M., Gotlib, I. H. ELSEVIER SCIENCE INC. 2024: S132-S133
  • Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning NATURE MENTAL HEALTH Bruin, W. B., Zhutovsky, P., van Wingen, G. A., Bas-Hoogendam, J., Groenewold, N. A., Hilbert, K., Winkler, A. M., Zugman, A., Agosta, F., Ahs, F., Andreescu, C., Antonacci, C., Asami, T., Assaf, M., Barber, J. P., Bauer, J., Bavdekar, S. Y., Beesdo-Baum, K., Benedetti, F., Bernstein, R., Bjorkstrand, J., Blair, R. J., Blair, K. S., Blanco-Hinojo, L., Bohnlein, J., Brambilla, P., Bressan, R. A., Breuer, F., Cano, M., Canu, E., Cardinale, E. M., Cardoner, N., Cividini, C., Cremers, H., Dannlowski, U., Diefenbach, G. J., Domschke, K., Doruyter, A. G. G., Dresler, T., Erhardt, A., Filippi, M., Fonzo, G. A., Freitag, G. F., Furmark, T., Ge, T., Gerber, A. J., Gosnell, S. N., Grabe, H. J., Grotegerd, D., Gur, R. C., Gur, R. E., Hamm, A. O., Han, L. K. M., Harper, J. C., Harrewijn, A., Heeren, A., Hofmann, D., Jackowski, A. P., Jahanshad, N., Jett, L., Kaczkurkin, A. N., Khosravi, P., Kingsley, E. N., Kircher, T., Kostic, M., Larsen, B., Lee, S., Leehr, E. J., Leibenluft, E., Lochner, C., Lui, S., Maggioni, E., Manfro, G. G., Mansson, K. N. T., Marino, C. E., Meeten, F., Milrod, B., Jovanovic, A., Mwangi, B., Myers, M. J., Neufang, S., Nielsen, J. A., Ohrmann, P. A., Ottaviani, C., Paulus, M. P., Perino, M. T., Phan, K., Poletti, S., Porta-Casteras, D., Pujol, J., Reinecke, A., Ringlein, G., Rjabtsenkov, P., Roelofs, K., Salas, R., Salum, G. A., Satterthwaite, T. D., Schrammen, E., Sindermann, L., Smoller, J. W., Soares, J. C., Stark, R., Stein, F., Straube, T., Straube, B., Strawn, J. R., Suarez-Jimenez, B., Sylvester, C. M., Talati, A., Thomopoulos, S. I., Tukel, R., van Nieuwenhuizen, H., Werwath, K., Wittfeld, K., Wright, B., Wu, M., Yang, Y., Zilverstand, A., Zwanzger, P., Blackford, J. U., Avery, S. N., Clauss, J. A., Lueken, U., Thompson, P. M., Pine, D. S., Stein, D. J., van der Wee, N. J. A., Veltman, D. J., Aghajani, M. 2024; 2 (1)
  • A systematic review and meta-analysis of resting-state fMRI in anxiety disorders: Need for data sharing to move the field forward. Journal of anxiety disorders Zugman, A., Jett, L., Antonacci, C., Winkler, A. M., Pine, D. S. 2023; 99: 102773

    Abstract

    Anxiety disorders are among the most prevalent psychiatric disorders. Neuroimaging findings remain uncertain, and resting state functional magnetic resonance (rs-fMRI) connectivity is of particular interest since it is a scalable functional imaging modality. Given heterogeneous past findings for rs-fMRI in anxious individuals, we characterize patterns across anxiety disorders by conducting a systematic review and meta-analysis. Studies were included if they contained at the time of scanning both a healthy group and a patient group. Due to insufficient study numbers, the quantitative meta-analysis only included seed-based studies. We performed an activation likelihood estimation (ALE) analysis that compared patients and healthy volunteers. All analyses were corrected for family-wise error with a cluster-level threshold of p < .05. Patients exhibited hypo-connectivity between the amygdala and the medial frontal gyrus, anterior cingulate cortex, and cingulate gyrus. This finding, however, was not robust to potential file-drawer effects. Though limited by strict inclusion criteria, our results highlight the heterogeneous nature of reported findings. This underscores the need for data sharing when attempting to detect reliable patterns of disruption in brain activity across anxiety disorders.

    View details for DOI 10.1016/j.janxdis.2023.102773

    View details for PubMedID 37741177