37 research outputs found
Cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion
Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety
Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1Â year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology
Development and Psychometric Validation of the Pandemic-Related Traumatic Stress Scale for Children and Adults
To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13â21 years) and adult self-report and caregiver-report on 3â12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3â12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively
Early life stress, prenatal secondhand smoke exposure, and the development of internalizing symptoms across childhood
Abstract Background Prior findings relating secondhand tobacco smoke (SHS) exposure and internalizing problems, characterized by heightened anxiety and depression symptoms, have been equivocal; effects of SHS on neurodevelopment may depend on the presence of other neurotoxicants. Early life stress (ELS) is a known risk factor for internalizing symptoms and is also often concurrent with SHS exposure. To date the interactive effects of ELS and SHS on childrenâs internalizing symptoms are unknown. We hypothesize that children with higher exposure to both prenatal SHS and ELS will have the most internalizing symptoms during the preschool period and the slowest reductions in symptoms over time. Methods The present study leveraged a prospective, longitudinal birth cohort of 564 Black and Latinx mothers and their children, recruited between 1998 and 2006. Cotinine extracted from cord and maternal blood at birth served as a biomarker of prenatal SHS exposure. Parent-reported Child Behavior Checklist (CBCL) scores were examined at four timepoints between preschool and eleven years-old. ELS exposure was measured as a composite of six domains of maternal stress reported at child age five. Latent growth models examined associations between SHS, ELS, and their interaction term with trajectories of childrenâs internalizing symptoms. In follow-up analyses, weighted quintile sum regression examined contributions of components of the ELS mixture to childrenâs internalizing symptoms at each time point. Results ELS interacted with SHS exposure such that higher levels of ELS and SHS exposure were associated with more internalizing symptoms during the preschool period (ÎČâ=â0.14, pâ=â0.03). The interaction between ELS and SHS was also associated with a less negative rate of change in internalizing symptoms over time (ÎČ=-0.02, pâ=â0.01). Weighted quintile sum regression revealed significant contributions of maternal demoralization and other components of the stress mixture to childrenâs internalizing problems at each age point (e.g., age 11 WQS ÎČâ=â0.26, pâ<â0.01). Conclusions Our results suggest that prior inconsistencies in studies of SHS on behavior may derive from unmeasured factors that also influence behavior and co-occur with exposure, specifically maternal stress during childrenâs early life. Findings point to modifiable targets for personalized prevention
Errorârelated brain activity associated with obsessiveâcompulsive symptoms in youth
Abstract Background Subclinical obsessiveâcompulsive symptoms (OCS) are common in children, and increase risk for later onset of obsessiveâcompulsive disorder (OCD). In pediatric patients with OCD, neuroimaging research implicates altered neural mechanisms for errorâprocessing, but whether abnormal brain response occurs with subclinical OCS remains poorly understood. Methods Using functional magnetic resonance imaging (fMRI), 113 youth (8â18 years; 45 female) from a community sample were scanned during an errorâeliciting Go/NoâGo task. OCS were assessed dimensionally using the obsessiveâcompulsive subscale of the Child Behavior Checklist. The association between OCS scores and errorârelated brain activity was examined at the wholeâbrain level. Results Lower OCS scores associated with stronger response to errors in dorsal anterior cingulate cortex (dACC), caudate, putamen, thalamus, and occipital cortex. Additionally, lower OCS related to higher capacity for inhibitory control, as indexed by greater accuracy on NoâGo trials during fMRI scanning. The relationship between lower OCS and better accuracy on NoâGo trials was mediated by greater errorârelated dACC activity. Conclusions The inverse relationship between OCS and errorârelated activity in the dACC and extended corticalâstriatalâthalamic circuitry may index an adaptive process by which subclinical OCS are minimized in youth. Further, these results identify an observable pattern of brain activity that tracks with subclinical OCS severity. Understanding the link between neural networks for error processing and the normal to abnormal range of OCS may pave the way for brainâbased strategies to identify children who are more likely to develop OCD and enable the targeting of preventive strategies to reduce risk
Cognitive Behavioral Therapy Normalizes FrontoParietal Activation in Unmedicated Patients With Pediatric Anxiety Disorders
Mindfulness-based Real-time fMRI Neurofeedback: A Randomized Controlled Trial to Optimize Dosing for Depressed Adolescents (Study Protocol)
Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. Adolescents (N=90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 minutes of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-minute mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495)
Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk
This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development