Exposure to community violence as a mechanism linking neighborhood disadvantage to amygdala reactivity and the protective role of parental nurturance.

Emerging literature links neighborhood disadvantage to altered neural function in regions supporting socioemotional and threat processing. Few studies, however, have examined the proximal mechanisms through which neighborhood disadvantage is associated with neural functioning. In a sample of 7- to 19-year-old twins recruited from disadvantaged neighborhoods (354 families, 708 twins; 54.5% boys; 78.5% White, 13.0% Black, 8.5% other racial/ethnic group membership), we found that exposure to community violence was related to increased amygdala reactivity during socioemotional processing and may be one mechanism linking neighborhood disadvantage to amygdala functioning. Importantly, parenting behavior appeared to modulate these effects, such that high parental nurturance buffered the effect of exposure to community violence on amygdala reactivity. These findings elucidate the potential impact of exposure to community violence on brain function and highlight the role parents can play in protecting youth from the neural effects of exposure to adversity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Why weight? Analytic approaches for large-scale population neuroscience data.

Population-based neuroimaging studies that feature complex sampling designs enable researchers to generalize their results more widely. However, several theoretical and analytical questions pose challenges to researchers interested in these data. The following is a resource for researchers interested in using population-based neuroimaging data. We provide an overview of sampling designs and describe the differences between traditional model-based analyses and survey-oriented design-based analyses. To elucidate key concepts, we leverage data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), a population-based sample of 11,878 9-10-year-olds in the United States. Analyses revealed modest sociodemographic discrepancies between the target population of 9-10-year-olds in the U.S. and both the recruited ABCD sample and the analytic sample with usable structural and functional imaging data. In evaluating the associations between socioeconomic resources (i.e., constructs that are tightly linked to recruitment biases) and several metrics of brain development, we show that model-based approaches over-estimated the associations of household income and under-estimated the associations of caregiver education with total cortical volume and surface area. Comparable results were found in models predicting neural function during two fMRI task paradigms. We conclude with recommendations for ABCD Study® users and users of population-based neuroimaging cohorts more broadly.

Socioeconomic resources are associated with distributed alterations of the brain's intrinsic functional architecture in youth.

Little is known about how exposure to limited socioeconomic resources (SER) in childhood gets "under the skin" to shape brain development, especially using rigorous whole-brain multivariate methods in large, adequately powered samples. The present study examined resting state functional connectivity patterns from 5821 youth in the Adolescent Brain Cognitive Development (ABCD) study, employing multivariate methods across three levels: whole-brain, network-wise, and connection-wise. Across all three levels, SER was associated with widespread alterations across the connectome. However, critically, we found that parental education was the primary driver of neural associations with SER. These parental education associations with the developing connectome exhibited notable concentrations in somatosensory and subcortical regions, and they were partially accounted for by home enrichment activities, child's cognitive abilities, and child's grades, indicating interwoven links between parental education, child stimulation, and child cognitive performance. These results add a new data-driven, multivariate perspective on links between household SER and the child's developing functional connectome.

Amygdala reactivity during socioemotional processing and cortisol reactivity to a psychosocial stressor.

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.

Deadly gun violence, neighborhood collective efficacy, and adolescent neurobehavioral outcomes.

Gun violence is a major public health problem and costs the United States $280 billion annually (1). Although adolescents are disproportionately impacted (e.g. premature death), we know little about how close adolescents live to deadly gun violence incidents and whether such proximity impacts their socioemotional development (2, 3). Moreover, gun violence is likely to shape youth developmental outcomes through biological processes-including functional connectivity within regions of the brain that support emotion processing, salience detection, and physiological stress responses-though little work has examined this hypothesis. Lastly, it is unclear if strong neighborhood social ties can buffer youth from the neurobehavioral effects of gun violence. Within a nationwide birth cohort of 3,444 youth (56% Black, 24% Hispanic) born in large US cities, every additional deadly gun violence incident that occurred within 500 meters of home in the prior year was associated with an increase in behavioral problems by 9.6%, even after accounting for area-level crime and socioeconomic resources. Incidents that occurred closer to a child's home exerted larger effects, and stronger neighborhood social ties offset these associations. In a neuroimaging subsample (N = 164) of the larger cohort, living near more incidents of gun violence and reporting weaker neighborhood social ties were associated with weaker amygdala-prefrontal functional connectivity during socioemotional processing, a pattern previously linked to less effective emotion regulation. Results provide spatially sensitive evidence for gun violence effects on adolescent behavior, a potential mechanism through which risk is biologically embedded, and ways in which positive community factors offset ecological risk.

The impact of neighborhood disadvantage on amygdala reactivity: Pathways through neighborhood social processes.

Youth growing up in disadvantaged neighborhoods are more likely than their advantaged peers to face negative behavioral and mental health outcomes. Although studies have shown that adversity can undermine positive development via its impact on the developing brain, few studies have examined the association between neighborhood disadvantage and neural function, and no study has investigated potential social mechanisms within the neighborhood that might link neighborhood disadvantage to altered neural function. The current study evaluated the association between neighborhood disadvantage and amygdala reactivity during socioemotional face processing. We also assessed whether and which neighborhood-level social processes were related to amygdala reactivity, and whether these social processes mediated or moderated the association between neighborhood disadvantage and altered amygdala reactivity. We examined these aims in a registered report, using a sample of twins aged 7-19 years (N = 354 families, 708 twins) recruited from birth records with enrichment for neighborhood disadvantage. Twins completed a socioemotional face processing fMRI task and a sample of unrelated participants from the twins' neighborhoods were also recruited to serve as informants on neighborhood social processes. We found that neighborhood disadvantage was associated with greater right amygdala reactivity to threat, but only when neighborhood informants perceived norms in the neighborhood to be more permissive regarding general safety and management. The findings from this research add to the growing literature highlighting the influence of neighborhood disadvantage on amygdala function and the ways that supportive social processes may buffer the impact of adversity on brain function.

Prospective longitudinal associations between harsh parenting and corticolimbic function during adolescence.

Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively collected longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS) (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala-PFC connectivity during angry face processing.

Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth.

General cognitive ability (GCA) is an individual difference dimension linked to important academic, occupational, and health-related outcomes and its development is strongly linked to differences in socioeconomic status (SES). Complex abilities of the human brain are realized through interconnections among distributed brain regions, but brain-wide connectivity patterns associated with GCA in youth, and the influence of SES on these connectivity patterns, are poorly understood. The present study examined functional connectomes from 5937 9- and 10-year-olds in the Adolescent Brain Cognitive Development (ABCD) multi-site study. Using multivariate predictive modeling methods, we identified whole-brain functional connectivity patterns linked to GCA. In leave-one-site-out cross-validation, we found these connectivity patterns exhibited strong and statistically reliable generalization at 19 out of 19 held-out sites accounting for 18.0% of the variance in GCA scores (cross-validated partial η2). GCA-related connections were remarkably dispersed across brain networks: across 120 sets of connections linking pairs of large-scale networks, significantly elevated GCA-related connectivity was found in 110 of them, and differences in levels of GCA-related connectivity across brain networks were notably modest. Consistent with prior work, socioeconomic status was a strong predictor of GCA in this sample, and we found that distributed GCA-related brain connectivity patterns significantly statistically mediated this relationship (mean proportion mediated: 15.6%, p < 2 × 10-16). These results demonstrate that socioeconomic status and GCA are related to broad and diffuse differences in functional connectivity architecture during early adolescence, potentially suggesting a mechanism through which socioeconomic status influences cognitive development.

Phenotypic and genetic markers of psychopathology in a population-based sample of older adults.

Although psychiatric phenotypes are hypothesized to organize into a two-factor internalizing-externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6003 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS). Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, attention deficit hyperactivity disorder) were not associated with any phenotypes, PGSs for major depressive disorder, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the variance explained in the general factor of psychopathology increased by twofold (from 1% to 2%) using the latent internalizing or latent one-factor PGSs, derived using weights from Genomic Structural Equation Modeling (SEM), compared with any of the individual PGSs. Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry. Alternative explanations are discussed, including methodological limitations of GWAS and phenotypic measurement of psychiatric outcome in large-scale population-based studies.

Beyond family-level adversities: Exploring the developmental timing of neighborhood disadvantage effects on the brain.

A growing literature suggests that adversity is associated with later altered brain function, particularly within the corticolimbic system that supports emotion processing and salience detection (e.g., amygdala, prefrontal cortex [PFC]). Although neighborhood socioeconomic disadvantage has been shown to predict maladaptive behavioral outcomes, particularly for boys, most of the research linking adversity to corticolimbic function has focused on family-level adversities. Moreover, although animal models and studies of normative brain development suggest that there may be sensitive periods during which adversity exerts stronger effects on corticolimbic development, little prospective evidence exists in humans. Using two low-income samples of boys (n = 167; n = 77), Census-derived neighborhood disadvantage during early childhood, but not adolescence, was uniquely associated with greater amygdala, but not PFC, reactivity to ambiguous neutral faces in adolescence and young adulthood. These associations remained after accounting for several family-level adversities (e.g., low family income, harsh parenting), highlighting the independent and developmentally specific neural effects of the neighborhood context. Furthermore, in both samples, indicators measuring income and poverty status of neighbors were predictive of amygdala function, suggesting that neighborhood economic resources may be critical to brain development.

An ecological approach to understanding the developing brain: Examples linking poverty, parenting, neighborhoods, and the brain.

We describe an ecological approach to understanding the developing brain, with a focus on the effects of poverty-related adversity on brain function. We articulate how combining multilevel ecological models from developmental science and developmental psychopathology with human neuroscience can inform our approach to understanding the developmental neuroscience of risk and resilience. To illustrate this approach, we focus on associations between poverty and brain function, the roles parents and neighborhoods play in this context, and the potential impact of developmental timing. We also describe the major challenges and needed advances in these areas of research to better understand how and why poverty-related adversity may impact the developing brain, including the need for: a population neuroscience approach with greater attention to sampling and representation, genetically informed and causal designs, advances in assessing context and brain function, caution in interpretation of effects, and a focus on resilience. Work in this area has major implications for policy and prevention, which are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Evaluation of a Longitudinal Family Stress Model in a Population-Based Cohort.

The Family Stress Model (FSM) is an influential family process model that posits that socioeconomic disadvantage impacts child outcomes via its effects on parents. Existing evaluations of the FSM are constrained by limited measures of socioeconomic disadvantage, cross-sectional research designs, and reliance on non-population-based samples. The current study tested the FSM in a subsample of the Fragile Families and Child Wellbeing Study (N = 2,918), a large population-based study of children followed from birth through age 9. We employed a longitudinal framework and used measures of socioeconomic disadvantage beyond economic resources. Although the hypothesized FSM pathways were identified in the longitudinal model (e.g., economic pressure at age 1 was associated with maternal distress at age 3, maternal distress at age 3 was associated with parenting behaviors at age 5), the effects of socioeconomic disadvantage at childbirth on youth socioemotional outcomes at age 9 did not operate through all of the hypothesized mediators. In longitudinal change models that accounted for the stability in constructs, multiple indicators of socioeconomic disadvantage at childbirth were indirectly associated with youth externalizing behaviors at age 9 via either economic pressure at age 1 or changes in maternal warmth from ages 3 to 5. Greater economic pressure at age 1, increases in maternal distress from ages 1 to 3, and decreases/increases in maternal warmth/harshness from ages 3 to 5 were also directly associated with increases in externalizing behaviors from ages 5 to 9. Results provide partial support for the FSM across the first decade of life.

Weakened Functional Connectivity Between the Amygdala and the Ventromedial Prefrontal Cortex Is Longitudinally Related to Psychopathic Traits in Low-Income Males During Early Adulthood.

Psychopathy is a complex disorder comprised of harmful personality traits and impulsive-lifestyle and antisocial behaviors. Weakened functional connectivity between limbic and prefrontal brain regions is thought to underlie impaired sensitivity to others' emotions that contribute to the interpersonal and affective personality traits associated with psychopathy. We tested whether weakened functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) during the processing of fearful, angry, and neutral facial expressions, was prospectively related to psychopathic traits in early adulthood. The sample included 167 low-income, racially diverse, urban males who completed an fMRI scan at age 20 and questionnaire measures at ages 20 and 22. Weakened amygdala-vmPFC functional connectivity to fearful, but not neutral or angry, faces at age 20 was related to higher psychopathic traits at age 22.

Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene-region aggregation techniques.

Sex differences in rates of depression are thought to contribute to sex differences in smoking initiation (SI) and number of cigarettes smoked per day (CPD). One hypothesis is that women smoke as a strategy to cope with anxiety and depression, and have difficulty quitting because of concomitant changes in hypothalamic-pituitary-adrenocortical (HPA) axis function during nicotine withdrawal states. Despite evidence of biological ties, research has not examined whether genetic factors that contribute to depression-smoking comorbidity differ by sex. We utilized two statistical aggregation techniques-polygenic scores (PGSs) and sequence kernel association testing-to assess the degree of pleiotropy between these behaviors and moderation by sex in the Health and Retirement Study (N = 8,086). At the genome-wide level, we observed associations between PGSs for depressive symptoms and SI, and measured SI and depressive symptoms (all p < .01). At the gene level, we found evidence of pleiotropy in FKBP5 for SI (p = .028), and sex-specific pleiotropy in females in NR3C2 (p = .030) and CHRNA5 (p = .025) for SI and CPD, respectively. Results suggest bidirectional associations between depression and smoking may be partially accounted for by shared genetic factors, and genetic variation in genes related to HPA-axis functioning and nicotine dependence may contribute to sex differences in SI and CPD.

The System for Coding Interactions and Family Functioning (SCIFF) in low-income and urban adolescents.

Reliable, brief, and cost-effective methods to assess parenting are critical for advancing etiological research and translational efforts within parenting science. In the current study, we adapted the System for Coding Interactions and Family Functioning (SCIFF) for use among a sample of mostly racial minority adolescents aged 15 years old, growing up in a low-income urban setting. A multiethnic team coded videotapes of a family interaction task designed to elicit conflict. First, we assessed the reliability of SCIFF codes (N = 187; 54% female; 77% African American). Second, we tested whether SCIFF codes assessing harsh parenting, positive parenting, dyadic conflict, and dyadic closeness converged with parent-child reports of the same constructs. Third we explored links between observed harsh and positive parenting in early childhood (ages 3 and 5) and SCIFF codes at age 15. Our training and SCIFF coding protocols produced high interrater reliability. In support of convergent validity, we found specificity in the associations between negative aspects of parenting across methods: the SCIFF harsh parenting and dyadic conflict codes uniquely converged with concurrent parent-child reports of the same constructs. There was a longitudinal cross-construct association between more observed harshness in early childhood and lower dyadic closeness at age 15. Finally, the convergence of the SCIFF codes with other parenting measures was similar by gender and for families living below or above 200% of the poverty line. A modified version of the SCIFF can be used with reliability in low-income urban samples with variation in gender and race. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Genetic influences on antisocial behavior: recent advances and future directions.

Understanding the etiology of antisocial behavior (i.e. violence, criminality, rule-breaking), is essential to the development of more effective prevention and intervention strategies. We provide a summary of the genetic correlates of antisocial behavior, drawing upon findings from behavioral, molecular, and statistical genetics. Across methodologies, our review highlights the centrality of environmental moderators of genetic effects, and how behavioral heterogeneity in antisocial behavior is an important consideration for genetic studies. We also review novel analytic techniques and neurogenetic approaches that can be used to examine how genetic variation predicts antisocial behavior. Finally, to illustrate how findings may converge across approaches, we describe pathways from genetic variability in oxytocin signaling to subtypes of antisocial behavior.

Amygdala reactivity as a marker of differential susceptibility to socioeconomic resources during early adulthood.

Models of differential susceptibility hypothesize that neural function may be a marker of differential susceptibility to context, but no studies have tested this hypothesis. Using a sample of 310 young men from low-income urban neighborhoods, this study investigated amygdala reactivity to facial expressions as a moderator of the relations between socioeconomic resources and later antisocial behavior (AB) and income. For individuals with high amygdala reactivity, greater socioeconomic resources at age 20 predicted less AB and greater income at age 22. For young men with low amygdala reactivity, however, socioeconomic resources at age 20 did not predict later outcomes. Amygdala reactivity to fearful facial expressions, key to the etiology of AB, moderated links between resources and AB. In contrast, amygdala reactivity more generally to multiple facial expressions moderated the effects of resources on later income attainment. Both interactions met rigorous quantitative criteria for patterns of differential susceptibility rather than diathesis stress or vantage sensitivity. Moreover, these associations remained significant after inclusion of socioeconomic resources during earlier developmental periods. These results suggest that greater amygdala reactivity to facial expressions is a marker of greater susceptibility to context, for better or for worse, during the transition to adulthood. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Amygdala functional connectivity during socioemotional processing prospectively predicts increases in internalizing symptoms in a sample of low-income, urban, young men.

Functional connectivity between the amygdala and the prefrontal cortex is critical for socioemotional processing, particularly during face processing. Though processing others' emotions is important for a myriad of complex social behaviors, more research is needed to understand how different types of emotional facial expressions differentially elicit connectivity of the amygdala with widespread neural regions. Moreover, though prior studies have reported cross-sectional associations between altered amygdala-prefrontal cortex functional connectivity and internalizing symptoms (e.g., depression, anxiety), few studies have examined whether amygdala functional connectivity is prospectively related to changes in these symptoms, with little work focusing on low-income men living in stressful contexts. The current study used psycho-physiological interaction analyses at the within-subjects level to examine how amygdala connectivity differed while participants viewed fearful, angry, and neutral faces. We used structural equation modeling at the between-subjects level, using extracted parameter estimates, to test whether amygdala connectivity during face processing predicted increases in internalizing psychopathology over time, controlling for earlier symptoms. An urban sample of 167 young men from low-income families was employed. Results indicated that negative connectivity between the amygdala and prefrontal regions was modulated by emotional face type. Neuronal activity in the cingulate and frontal cortices was connected to amygdala reactivity during fearful and neutral, but not angry, face processing. Moreover, weaker left amygdala-left middle frontal gyrus negative connectivity when viewing fearful faces and stronger right amygdala-left inferior frontal gyrus negative connectivity when viewing neutral faces at age 20 both predicted increases in internalizing behaviors from age 20 to age 22. Our findings show that amygdala-prefrontal cortex connectivity can predict the persistence of internalizing symptoms among high-risk participants over time but suggest that these patterns may differ depending on the emotional stimuli examined.

The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

BACKGROUND: Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. METHODS: Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling (CRHR1) was examined as a moderator of pathways to amygdala reactivity. RESULTS: Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1. CONCLUSIONS: These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.