Adolescent functional network connectivity prospectively predicts adult anxiety symptoms related to perceived COVID-19 economic adversity.

BACKGROUND: Stressful events, such as the COVID-19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population-based sample (N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences. METHODS: Data-driven network-based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self-reported at ages 15, 17, and 21 (during COVID-19). During COVID-19, participants reported on pandemic-related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup-adversity interaction were tested to predict change in symptoms over time. RESULTS: Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (ß = .138, p = .042), and this result remained after adjusting for additional covariates (ß = .194, p = .023). Furthermore, there was a subgroup-adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (ß = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (ß = .237, p = .021). CONCLUSIONS: A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.

School connectedness as a protective factor against childhood exposure to violence and social deprivation: A longitudinal study of adaptive and maladaptive outcomes.

School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.

Differential Developmental Associations of Material Hardship Exposure and Adolescent Amygdala-Prefrontal Cortex White Matter Connectivity.

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala-prefrontal, but not hippocampus-prefrontal or hippocampus-amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala-orbitofrontal (OFC) and greater amygdala-subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala-subgenual ACC) and reduced (amygdala-OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala-OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.

Amygdala-prefrontal cortex white matter tracts are widespread, variable and implicated in amygdala modulation in adolescents.

The amygdala is critically involved in processing emotion. Through bidirectional connections, the prefrontal cortex (PFC) is hypothesized to influence amygdala reactivity. However, research that elucidates the nature of amygdala-PFC interactions - through mapping amygdala-prefrontal tracts, quantifying variability among tracts, and linking this variability to amygdala activation - is lacking. Using probabilistic tractography to map amygdala-prefrontal white matter connectivity in 142 adolescents, the present study found that white matter connectivity was greater between the amygdala and the subgenual cingulate, orbitofrontal (OFC), and dorsomedial (dmPFC) prefrontal regions than with the dorsal cingulate and dorsolateral regions. Then, using a machine-learning regression, we found that greater amygdala-PFC white matter connectivity was related to attenuated amygdala reactivity. This effect was driven by amygdala white matter connectivity with the dmPFC and OFC, supporting implicit emotion processing theories which highlight the critical role of these regions in amygdala regulation. This study is among the first to map and compare specific amygdala-prefrontal white matter tracts and to relate variability in connectivity to amygdala activation, particularly among a large sample of adolescents from a well-sampled study. By examining the association between specific amygdala-PFC tracts and amygdala activation, the present study provides novel insight into the nature of this emotion-based circuit.

Assessing performance of ZCTA-level and Census Tract-level social and environmental risk factors in a model predicting hospital events.

Predictive analytics are used in primary care to efficiently direct health care resources to high-risk patients to prevent unnecessary health care utilization and improve health. Social determinants of health (SDOH) are important features in these models, but they are poorly measured in administrative claims data. Area-level SDOH can be proxies for unavailable individual-level indicators, but the extent to which the granularity of risk factors impacts predictive models is unclear. We examined whether increasing the granularity of area-based SDOH features from ZIP code tabulation area (ZCTA) to Census Tract strengthened an existing clinical prediction model for avoidable hospitalizations (AH events) in Maryland Medicare fee-for-service beneficiaries. We created a person-month dataset for 465,749 beneficiaries (59.4% female; 69.8% White; 22.7% Black) with 144 features indexing medical history and demographics using Medicare claims (September 2018 through July 2021). Claims data were linked with 37 SDOH features associated with AH events from 11 publicly-available sources (e.g., American Community Survey) based on the beneficiaries' ZCTA and Census Tract of residence. Individual AH risk was estimated using six discrete time survival models with different combinations of demographic, condition/utilization, and SDOH features. Each model used stepwise variable selection to retain only meaningful predictors. We compared model fit, predictive performance, and interpretation across models. Results showed that increasing the granularity of area-based risk factors did not dramatically improve model fit or predictive performance. However, it did affect model interpretation by altering which SDOH features were retained during variable selection. Further, the inclusion of SDOH at either granularity level meaningfully reduced the risk that was attributed to demographic predictors (e.g., race, dual-eligibility for Medicaid). Differences in interpretation are critical given that this model is used by primary care staff to inform the allocation of care management resources, including those available to address drivers of health beyond the bounds of traditional health care.

Antisocial behavior is associated with reduced frontoparietal network efficiency in youth.

Youth antisocial behavior (AB) is associated with deficits in socioemotional processing, reward and threat processing and executive functioning. These deficits are thought to emerge from differences in neural structure, functioning and connectivity, particularly within the default, salience and frontoparietal networks. However, the relationship between AB and the organization of these networks remains unclear. To address this gap, the current study applied unweighted, undirected graph analyses to resting-state functional magnetic resonance imaging data in a cohort of 161 adolescents (95 female) enriched for exposure to poverty, a risk factor for AB. As prior work indicates that callous-unemotional (CU) traits may moderate the neurocognitive profile of youth AB, we examined CU traits as a moderator. Using multi-informant latent factors, AB was found to be associated with less efficient frontoparietal network topology, a network associated with executive functioning. However, this effect was limited to youth at low or mean levels of CU traits, indicating that these neural differences were specific to those high on AB but not CU traits. Neither AB, CU traits nor their interaction was significantly related to default or salience network topologies. Results suggest that AB, specifically, may be linked with shifts in the architecture of the frontoparietal network.

Early childhood household instability, adolescent structural neural network architecture, and young adulthood depression: A 21-year longitudinal study.

Unstable and unpredictable environments are linked to risk for psychopathology, but the underlying neural mechanisms that explain how instability relate to subsequent mental health concerns remain unclear. In particular, few studies have focused on the association between instability and white matter structures despite white matter playing a crucial role for neural development. In a longitudinal sample recruited from a population-based study (N = 237), household instability (residential moves, changes in household composition, caregiver transitions in the first 5 years) was examined in association with adolescent structural network organization (network integration, segregation, and robustness of white matter connectomes; Mage = 15.87) and young adulthood anxiety and depression (six years later). Results indicate that greater instability related to greater global network efficiency, and this association remained after accounting for other types of adversity (e.g., harsh parenting, neglect, food insecurity). Moreover, instability predicted increased depressive symptoms via increased network efficiency even after controlling for previous levels of symptoms. Exploratory analyses showed that structural connectivity involving the left fronto-lateral and temporal regions were most strongly related to instability. Findings suggest that structural network efficiency relating to household instability may be a neural mechanism of risk for later depression and highlight the ways in which instability modulates neural development.

Mapping frontostriatal white matter tracts and their association with reward-related ventral striatum activation in adolescence.

The ventral striatum (VS) is implicated in reward processing and motivation. Human and non-human primate studies demonstrate that the VS and prefrontal cortex (PFC), which comprise the frontostriatal circuit, interact to influence motivated behavior. However, there is a lack of research that precisely maps and quantifies VS-PFC white matter tracts. Moreover, no studies have linked frontostriatal white matter to VS activation. Using a multimodal neuroimaging approach with diffusion MRI (dMRI) and functional MRI (fMRI), the present study had two objectives: 1) to chart white matter tracts between the VS and specific PFC structures and 2) assess the association between the degree of VS-PFC white matter tract connectivity and VS activation in 187 adolescents. White matter connectivity was assessed with probabilistic tractography and functional activation was examined with two fMRI tasks (one task with social reward and another task using monetary reward). We found widespread but variable white matter connectivity between the VS and areas of the PFC, with the anterior insula and subgenual cingulate cortex demonstrating the greatest degree of connectivity with the VS. VS-PFC structural connectivity was related to functional activation in the VS though activation depended on the specific PFC region and reward task.

Ecological stress, amygdala reactivity, and internalizing symptoms in preadolescence: Is parenting a buffer?

Ecological stress during adolescent development may increase the sensitivity to negative emotional processes that can contribute to the onset and progression of internalizing behaviors during preadolescence. Although a small number of studies have considered the link among the relations between ecological stress, amygdala reactivity, and internalizing symptoms in childhood and adolescence, these studies have largely been small, cross-sectional, and often do not consider unique roles of parenting or sex. In the current study, we evaluated the interrelations between ecological stress, amygdala reactivity, subsequent internalizing symptoms, and the moderating roles of parenting and sex among 9- and 10-year-old preadolescents from the Adolescent Brain Cognitive Development (ABCD) Study ®. A subset of participants who met a priori quality control criteria for bilateral amygdala activation during the EN-back faces versus places contrast (N = 7,385; Mean Age = 120 months, SD = 7.52; 49.5% Female) were included in the study. A confirmatory factor analysis was performed to create a latent variable of ecological stress, and multiple structural equation models were tested to evaluate the association among baseline ecological stress and internalizing symptoms one year later, the mediating role of amygdala reactivity, and moderating effects of parental acceptance and sex. The results revealed a significant association between ecological stress and subsequent internalizing symptoms, which was greater in males than females. There was no association between amygdala reactivity during the Faces versus Places contrast and ecological stress or subsequent internalizing symptoms, and no mediating role of amygdala or moderating effect of parental acceptance on the association between ecological stress and internalizing symptoms. An alternative mediation model was tested which revealed that there was a small mediating effect of parental acceptance on the association between ecological stress and internalizing symptoms, demonstrating lower internalizing symptoms among preadolescents one year later. Given the lack of association in brain function, ecological stress and internalizing symptoms in preadolescents in this registered report, effects from comparable small studies should be reconsidered in larger samples.

WITHDRAWN:Childhood violence exposure and social deprivation predict adolescent amygdala-orbitofrontal cortex white matter connectivity.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Childhood violence exposure and social deprivation predict adolescent amygdala-orbitofrontal cortex white matter connectivity.

Childhood adversity is heterogeneous with potentially distinct dimensions of violence exposure and social deprivation. These dimensions may differentially shape emotion-based neural circuitry, such as amygdala-PFC white matter connectivity. Amygdala-orbitofrontal cortex (OFC) white matter connectivity has been linked to regulation of the amygdala's response to emotional stimuli. Using a preregistered analysis plan, we prospectively examined the effects of childhood exposure to two dimensions of adversity, violence exposure and social deprivation, on the adolescent amygdala-PFC white matter connectivity. We also reproduced the negative correlation between amygdala-PFC white matter connectivity and amygdala activation to threat faces. 183 15-17-year-olds were recruited from the Fragile Families and Child Wellbeing Study - a longitudinal, birth cohort, sample of predominantly low-income youth. Probabilistic tractography revealed that childhood violence exposure and social deprivation interacted to predict the probability of adolescent right hemisphere amygdala-OFC white matter connectivity. High violence exposure with high social deprivation related to less amygdala-OFC white matter connectivity. Violence exposure was not associated with white matter connectivity when social deprivation was at mean or low levels (i.e., relatively socially supportive contexts). Therefore, social deprivation may exacerbate the effects of childhood violence exposure on the development of white matter connections involved in emotion processing and regulation. Conversely, social support may buffer against them.

Childhood violence exposure and social deprivation are linked to adolescent threat and reward neural function.

BACKGROUND: Childhood adversity is, unfortunately, highly prevalent and strongly associated with later psychopathology. Recent theories posit that two dimensions of early adversity, threat and deprivation, have distinct effects on brain development. The current study evaluated whether violence exposure (threat) and social deprivation (deprivation) were associated with adolescent amygdala and ventral striatum activation, respectively, in a prospective, well-sampled, longitudinal cohort using a pre-registered, open science approach. METHODS: One hundred and sixty-seven adolescents from the Fragile Families and Child Wellbeing Study completed functional magnetic resonance imaging (fMRI) scanning. Prospective longitudinal data from ages 3, 5 and 9 years were used to create indices of childhood violence exposure and social deprivation. We evaluated whether these dimensions were associated with adolescent brain function in response to threatening and rewarding faces. RESULTS: Childhood violence exposure was associated with decreased amygdala habituation (i.e. more sustained activation) and activation to angry faces in adolescence, whereas childhood social deprivation was associated with decreased ventral striatum activation to happy faces in adolescence. These associations held when adjusting for the other dimension of adversity (e.g., adjusting for social deprivation when examining associations with violence exposure), the interaction of the two dimensions of adversity, gender, internalizing psychopathology, and current life stress. CONCLUSIONS: Consistent with recent theories, different forms of early adversity were associated with region-specific differences in brain activation.

Association of Childhood Violence Exposure With Adolescent Neural Network Density.

Importance: Adverse childhood experiences are a public health issue with negative sequelae that persist throughout life. Current theories suggest that adverse childhood experiences reflect underlying dimensions (eg, violence exposure and social deprivation) with distinct neural mechanisms; however, research findings have been inconsistent, likely owing to variability in how the environment interacts with the brain. Objective: To examine whether dimensional exposure to childhood adversity is associated with person-specific patterns in adolescent resting-state functional connectivity (rsFC), defined as synchronized activity across brain regions when not engaged in a task. Design, Setting, and Participants: A sparse network approach in a large sample with substantial representation of understudied, underserved African American youth was used to conduct an observational, population-based longitudinal cohort study. A total of 183 adolescents aged 15 to 17 years from Detroit, Michigan; Toledo, Ohio; and Chicago, Illinois, who participated in the Fragile Families and Child Wellbeing Study were eligible for inclusion. Environmental data from birth to adolescence were collected via telephone and in-person interviews, and neuroimaging data collected at a university lab. The study was conducted from February 1, 1998, to April 26, 2017, and data analysis was performed from January 3, 2019, to May 22, 2020. Exposures: Composite variables representing violence exposure and social deprivation created from primary caregiver reports on children at ages 3, 5, and 9 years. Main Outcomes and Measures: Resting-state functional connectivity person-specific network metrics (data-driven subgroup membership, density, and node degree) focused on connectivity among a priori regions of interest in 2 resting-state networks (salience network and default mode) assessed with functional magnetic resonance imaging. Results: Of the 183 eligible adolescents, 175 individuals (98 girls [56%]) were included in the analysis; mean (SD) age was 15.88 (0.53) years and 127 participants (73%) were African American. Adolescents with high violence exposure were 3.06 times more likely (95% CI, 1.17-8.92) to be in a subgroup characterized by high heterogeneity (few shared connections) and low network density (sparsity). Childhood violence exposure, but not social deprivation, was associated with reduced rsFC density (ß = -0.25; 95% CI, -0.41 to -0.05; P = .005), with fewer salience network connections (ß = -0.26; 95% CI, -0.43 to -0.08; P = .005) and salience network-default mode connections (ß = -0.20; 95% CI, -0.38 to -0.03; P = .02). Violence exposure was associated with node degree of right anterior insula (ß = -0.29; 95% CI, -0.47 to -0.12; P = .001) and left inferior parietal lobule (ß = -0.26; 95% CI, -0.44 to -0.09; P = .003). Conclusions and Relevance: The findings of this study suggest that childhood violence exposure is associated with adolescent neural network sparsity. A community-detection algorithm, blinded to child adversity, grouped youth exposed to heightened violence based only on patterns of rsFC. The findings may have implications for understanding how dimensions of adverse childhood experiences impact individualized neural development.