Search

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.

BackgroundStructural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded.MethodsThe sample consisted of 10 645 youth aged 9–10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance.Resultsp exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity.ConclusionsIn this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

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.

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 −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.

Exposure in utero to particulate matter (PM2.5 and PM10) is associated with maladaptive health outcomes. Although exposure to prenatal PM2.5 and PM10 has cord blood DNA methylation signatures at birth, signature persistence into childhood and saliva cross-tissue applicability has not been tested. In the Fragile Families and Child Wellbeing Study, a United States 20-city birth cohort, average residential PM2.5 and PM10 during the three months prior to birth was estimated using air quality monitors with inverse distance weighting. Saliva DNA methylation at ages 9 (n = 749) and 15 (n = 793) was measured using the Illumina HumanMethylation 450 k BeadArray. Cumulative DNA methylation scores for particulate matter were estimated by weighting participant DNA methylation at each site by independent meta-analysis effect estimates and standardizing the sums. Using a mixed-effects regression analysis, we tested the associations between cumulative DNA methylation scores at ages 9 and 15 and PM exposure during pregnancy, adjusted for child sex, age, race/ethnicity, maternal income-to-needs ratio, nonmartial birth status, and saliva cell-type proportions. Our study sample was 50.5% male, 56.3% non-Hispanic Black, and 19.8% Hispanic, with a median income-to-needs ratio of 1.4. Mean exposure levels for PM2.5 were 27.9 μg/m3/day (standard deviation: 7.0; 23.7% of observations exceeded safety standards) and for PM10 were 15.0 μg/m3/day (standard deviation: 3.1). An interquartile range increase in PM2.5 exposure (10.73 μg/m3/day) was associated with a −0.0287 standard deviation lower cumulative DNA methylation score for PM2.5 (95% CI: −0.0732, 0.0158, p = 0.20) across all participants. An interquartile range increase in PM10 exposure (3.20 μg/m3/day) was associated with a −0.1472 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: −0.3038, 0.0095, p = 0.06) across all participants. The PM10 findings were driven by the age 15 subset where an interquartile range increase in PM10 exposure was associated with a −0.024 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: −0.043, −0.005, p = 0.012). Findings were robust to adjustment for PM exposure at ages 1 and 3. In utero PM10-associated DNA methylation differences were identified at age 15 in saliva. Benchmarking the timing and cell-type generalizability is critical for epigenetic exposure biomarker assessment.

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.

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).

Depression results from the interaction between genetic risk and exposure to environmental stressors. Efforts to study the joint effects of genes and environments on depression have largely focused on candidate gene approaches that rely on single genetic variants to characterize global gene function. Gene-region analyses, by contrast, evaluate the aggregate association between a set of genetic variants and a phenotype, and can be applied to gene x environment interaction models of depression. This chapter describes the utility and implementation of gene-region analyses, provides empirical examples of how these approaches have been used to study how genes increase risk for depression, and highlights several future directions for gene-region research that will enrich our understanding of the etiology of depression.

Manuscript in press at Development & Psychopathology (Submitted 8/17/2020, Accepted 11/08/2020). 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 (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

Introduction: Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the P factor. Questions remain, however, about meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. Methods: The sample consisted of 11,875 youth aged 9 to 10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. P, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including: demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report and behavioral task performance.Results: P exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. Conclusions: In this largest study of hierarchical models of psychopathology to date, we found that P, INT, and EXT exhibit well differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori internalizing and externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of P, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

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). 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, though 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 prefrontal cortex, 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.

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.

Psychopathy is a complex disorder consisting 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 a functional MRI 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.

Alzheimer’s disease and its related dementias (ADRD) are debilitating neurodegenerative diseases. As nearly two-thirds of persons diagnosed with Alzheimer’s disease are women, more research is needed to understand sex differences in the biological mechanisms that underlie ADRD. Depression is a risk factor for Alzheimer’s disease and higher rates of depression among women, compared to men, suggest that depression-related phenotypes and underlying biological factors may contribute to sex differences in ADRD. Using the Health and Retirement Study (N = 9908, European ancestry), a US panel-cohort study, the current analysis leverages Mendelian randomization techniques to assess sex-specific inferred causality of depressive symptoms on odds of dementia. All analyses assess most recent cognition and account for sex, education, study cohort, age and year of most recent cognition visit, and genetic ancestry principal components. A one standard deviation increase in depressive polygenic score was associated with 1.11 times higher odds of dementia (95% confidence interval: 1.02-1.21) relative to normal cognition. Each additional endorsed depressive symptom was associated with 1.13 times higher odds of dementia (95% confidence interval: 1.09-1.18) relative to normal cognition. Using the depression genetic instrument, a significant inferred causal relationship was observed between depressive symptoms and dementia (P=0.01, 1.73 odds ratio, 95% confidence interval: 1.12-2.67). When stratified by sex, this relationship was only significant in females (P=0.02, 1.76 odds ratio, 95% confidence interval: 1.08-2.87). These findings demonstrate that depressive symptoms are likely causally related to dementia, and this relationship is most pronounced in females.

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 (SKAT)—to assess the degree of pleiotropy between these behaviors and moderation by sex in the Health and Retirement Study (HRS) (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 < 0.01). At the gene level, we found evidence of pleiotropy in FKBP5 for SI (p=0.028), and sex-specific pleiotropy in females in NR3C2 (p=0.030) and CHRNA5 (p=0.025) 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 state of science has increasingly valued interdisciplinary training and research. As an early-stage investigator, interdisciplinary research, such as that supported by the Research Centers Collaborative Network through the National Institute on Aging, provides valuable opportunities to connect researchers across disciplinary boundaries. This program encourages researchers use their diverse training experiences to tackle difficult questions in aging research and forge scholarly relationship that advance the state of science through creative problem-solving and a spectrum of interdisciplinary perspectives. This presentation describes a recently funded project to examine sex differences in aging outcomes using genetics, depression, and impaired cognition with polygenic and gene-region aggregation techniques. We will highlight the benefits and opportunities of the Research Centers Collaborative Network pilot grant to this highly interdisciplinary work, co-lead by early-stage investigators.

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).

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.

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.

We examined the longitudinal associations between prenatal tobacco smoke exposure (PSE) and attention-deficit hyperactivity disorder (ADHD) symptom domains in adolescence and young adulthood. A sample of girls with ADHD combined presentation (N=93), ADHD predominantly inattentive presentation (N=47), and matched comparisons (N= 88) was assessed prospectively. Symptoms of hyperactivity/impulsivity (HI), inattention (IA), and oppositionality (oppositional defiant disorder) were measured via multiple informants 5 (M age =14 years; retention rate =92%) and 10 years (M age =20 years; retention rate =95%) following childhood ascertainment. PSE was captured via maternal self-report. We used linear regressions to examine the prediction from PSE to both HI and IA in adolescence and early adulthood after stringent control of relevant confounding variables. PSE significantly predicted HI during adolescence and young adulthood across multiple informants but did not predict IA at either wave. Symptoms of HI may have partial etiological independence from IA symptoms.

This pilot study examined the potential impact of a perinatal adaptation to Child-Parent Psychotherapy (CPP), an evidence-based treatment for traumatized mother–child dyads, on maternal functioning 6 months post-partum among women with history of complex trauma and current intimate partner abuse. Pregnant women (n = 64) enrolled during the third trimester of their pregnancy (Mean gestational age = 27.48 weeks, range of 12 to 42) and participated in weekly perinatal CPP sessions until their infant was 6 months old. Women completed measures of trauma history, depression, posttraumatic stress symptoms (PTSS), and child-rearing attitudes at pre- and post-treatment. Results showed decreases in depression and PTSS from pre- to post-treatment assessments, as well as an increase in positive child-rearing attitudes. As hypothesized, women with low maternal-fetal attachment demonstrated the greatest improvement in depression, PTSS, and child-rearing attitudes compared to women with high maternal-fetal attachment. T...

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. 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 1.5 to 20 years of age, multimethod assessments of adversities were examined at 2 and 12 years of age. At 20 years of age, amygdala reactivity to emotional facial expressions was assessed using functional magnetic resonance imaging, and symptoms of antisocial personality disorder were assessed via the Structured Clinical Interview for DSM. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Results Observed parenting and neighborhood deprivation at 2 years of age each uniquely predicted amygdala reactivity to emotional faces at 20 years of age over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically significant symptoms of antisocial behavior 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 antisocial behavior. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

This study investigates the creation of polygenic scores (PGS)s for human population research. PGSs are a linear, usually weighted, combination of risk alleles that estimate the cumulative genetic risk of an individual for a particular trait. While conceptually simple, there are numerous ways to estimate PGSs, not all achieving the same end goals. In this paper, we systematically investigate the impact of four key decisions in the building of PGSs from published genome-wide association meta-analysis results: 1) whether to use single nucleotide polymorphisms (SNPs) assessed by imputation, 2) criteria for selecting which SNPs to include in the score, 3) whether to account for linkage disequilibrium (LD), and 4) if accounting for LD, which type of method best captures the correlation structure among SNPs (i.e. clumping vs. pruning). Using the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal panel study of Americans over the age of 50, we examine the predictive ability as well as the variability and co-variability in PGSs arising from these different estimation approaches. We examine four traits with large published and replicated genome-wide association studies (height, body mass index, educational attainment, and depression). Our central finding demonstrates PGSs that include all available SNPs either explain the most amount of variation in an outcome or are not significantly different than the PGSs that does. Thus, for reproducibility through rigor and transparency, we recommend that researchers include a PGS with all available SNPs as a reference, and provide substantial justification for using alternative methods.

We examined the longitudinal associations between prenatal tobacco smoke exposure (PSE) and attention-deficit hyperactivity disorder (ADHD) symptom domains in adolescence and young adulthood. A sample of girls with ADHD combined presentation (N=93), ADHD predominantly inattentive presentation (N=47), and matched comparisons (N= 88) was assessed prospectively. Symptoms of hyperactivity/impulsivity (HI), inattention (IA), and oppositionality (oppositional defiant disorder) were measured via multiple informants 5 (M age =14 years; retention rate =92%) and 10 years (M age =20 years; retention rate =95%) following childhood ascertainment. PSE was captured via maternal self-report. We used linear regressions to examine the prediction from PSE to both HI and IA in adolescence and early adulthood after stringent control of relevant confounding variables. PSE significantly predicted HI during adolescence and young adulthood across multiple informants but did not predict IA at either wave. Symptoms of HI may have partial etiological independence from IA symptoms.

Neuroimaging has suggested that amygdala reactivity to emotional facial expressions is associated with antisocial behavior (AB), particularly among those high on callous–unemotional (CU) traits. To investigate this association and potential moderators of this relationship, including task/stimuli effects, subregional anatomy of the amygdala, and participant race, we used fMRI in a sample of 167 racially diverse 20-year-old men from low-income families. We found that AB, but not CU traits, was negatively related to amygdala reactivity to fearful faces. This result was specific to fearful faces and strongest in the centromedial subregion of the amygdala. Arrest record was positively related to basolateral amygdala reactivity to fearful and angry faces. Results were strongest among those identified as African American and not present in those identified as European American. Our findings suggest substantial complexity in the relationship between amygdala function and AB reflecting moderating effects of task stimulus, subregional anatomy, and race.

We examined whether maltreatment experienced in childhood and/or adolescence prospectively predicts young adult functioning in a diverse and well-characterized sample of females with childhood-diagnosed attention-deficit/hyperactivity disorder (N = 140). Participants were part of a longitudinal study and carefully evaluated in childhood, adolescence, and young adulthood (Mage = 9.6, 14.3, and 19.7 years, respectively), with high retention rates across time. A thorough review of multisource data reliably established maltreatment status for each participant (Mκ = 0.78). Thirty-two (22.9%) participants experienced at least one maltreatment type (physical abuse, sexual abuse, or neglect). Criterion variables included a broad array of young adult measures of functioning gleaned from multiple-source, multiple-informant instruments. With stringent statistical control of demographic, prenatal, and family status characteristics as well as baseline levels of the criterion variable in question, maltreated participants were significantly more impaired than nonmaltreated participants with respect to self-harm (suicide attempts), internalizing symptomatology (anxiety and depression), eating disorder symptomatology, and well-being (lower overall self-worth). Effect sizes were medium. Comprising the first longitudinal evidence linking maltreatment with key young adult life impairments among a carefully diagnosed and followed sample of females with attention-deficit/hyperactivity disorder, these findings underscore the clinical importance of trauma experiences within this population.