Atypical empathic responses in adolescents with aggressive conduct disorder: A functional MRI investigation

Abstract Because youth with aggressive conduct disorder (CD) often inflict pain on others, it is important to determine if they exhibit atypical empathic responses to viewing others in pain. In this initial functional magnetic resonance imaging (fMRI) study, 8 adolescents with aggressive CD and 8 matched controls were scanned while watching animated visual stimuli depicting other people experiencing pain or not experiencing pain. Furthermore, these situations involved either an individual whose pain was caused by accident or an individual whose pain was inflicted on purpose by another person. After scanning, participants rated how painful the situations were. In both groups the perception of others in pain was associated with activation of the pain matrix, including the ACC, insula, somatosensory cortex, supplementary motor area and periaqueductal gray. The pain matrix was activated to a significantly greater extent in participants with CD, who also showed strong amygdala, ventral striatum, and temporal pole activation. When watching situations in which pain was intentionally inflicted, control youth also exhibited signal increase in the medial prefrontal frontal cortex, lateral obitofrontal cortex, and temporoparietal junction, whereas youth with CD only exhibited activation in the insula. Furthermore, connectivity analyses demonstrated that youth with CD exhibited less amygdala/prefrontal coupling when watching pain inflicted by another than did control youth. These preliminary findings suggest that youth with aggressive CD exhibit an atypical pattern of neural response to viewing others in pain that should be explored in further studies

Is Maternal Smoking During Pregnancy a Causal Environmental Risk Factor for Adolescent Antisocial Behavior? Testing Etiological Theories and Assumptions

Background—Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design

The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology

Common genetic risk variants have been implicated in the etiology of clinical ADHD diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric problems, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing and internalizing symptoms, using structural equation modelling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing and depressive symptoms (R2=0.26%-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading=0.50, range=0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~1% (p-value<0.0001) of the variance in the general psychopathology factor and ~0.50% (p-value<0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms

Evidence and theory for lower rates of depression in larger US urban areas

It is commonly assumed that cities are detrimental to mental health. However, the evidence remains inconsistent and at most, makes the case for differences between rural and urban environments as a whole. Here, we propose a model of depression driven by an individual’s accumulated experience mediated by social networks. The connection between observed systematic variations in socioeconomic networks and built environments with city size provides a link between urbanization and mental health. Surprisingly, this model predicts lower depression rates in larger cities. We confirm this prediction for US cities using four independent datasets. These results are consistent with other behaviors associated with denser socioeconomic networks and suggest that larger cities provide a buffer against depression. This approach introduces a systematic framework for conceptualizing and modeling mental health in complex physical and social networks, producing testable predictions for environmental and social determinants of mental health also applicable to other psychopathologies

White Matter Microstructure and the General Psychopathology Factor in Children

Objective: Co-occurrence of behavioral and emotional problems in childhood is widespread, and previous studies have suggested that this reflects vulnerability to experience a range of psychiatric problems, often termed a general psychopathology factor. However, the neurobiological substrate of this general factor is not well understood. We tested the hypothesis that lower overall white matter microstructure is associated with higher levels of the general psychopathology factor in children and less with specific factors. Method: Global white matter microstructure at age 10 years was related to general and specific psychopathology factors. These factors were estimated using a latent bifactor model with multiple informants and instruments between ages 6 and 10 years in 3,030 children from the population-based birth cohort Generation R. The association of global white matter microstructure and the psychopathology factors was examined with a structural equation model adjusted for sex, age at scan, age at psychopathology assessment, parental education/income, and genetic ancestry. Results: A 1-SD increase of the global white matter factor was associated with a β = −0.07SD (standard error [SE] = 0.02, p < .01) decrease in general psychopathology. In contrast, a 1-SD increase of white matter microstructure predicted an increase of β = +0.07 SD (SE = 0.03, p < .01) specific externalizing factor levels. No association was found with the specific internalizing and specific attention factor. Conclusion: The results suggest that general psychopathology in childhood is related to white matter structure across the brain and not only to specific tracts. Taking into account general psychopathology may also help reveal neurobiological mechanisms behind specific symptoms that are otherwise obscured by comorbidity

Multivariate analytical approaches for investigating brain-behavior relationships

BackgroundMany studies of brain-behavior relationships rely on univariate approaches where each variable of interest is tested independently, which does not allow for the simultaneous investigation of multiple correlated variables. Alternatively, multivariate approaches allow for examining relationships between psychopathology and neural substrates simultaneously. There are multiple multivariate methods to choose from that each have assumptions which can affect the results; however, many studies employ one method without a clear justification for its selection. Additionally, there are few studies illustrating how differences between methods manifest in examining brain-behavior relationships. The purpose of this study was to exemplify how the choice of multivariate approach can change brain-behavior interpretations.MethodWe used data from 9,027 9- to 10-year-old children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) to examine brain-behavior relationships with three commonly used multivariate approaches: canonical correlation analysis (CCA), partial least squares correlation (PLSC), and partial least squares regression (PLSR). We examined the associations between psychopathology dimensions including general psychopathology, attention-deficit/hyperactivity symptoms, conduct problems, and internalizing symptoms with regional brain volumes.ResultsThe results of CCA, PLSC, and PLSR showed both consistencies and differences in the relationship between psychopathology symptoms and brain structure. The leading significant component yielded by each method demonstrated similar patterns of associations between regional brain volumes and psychopathology symptoms. However, the additional significant components yielded by each method demonstrated differential brain-behavior patterns that were not consistent across methods.ConclusionHere we show that CCA, PLSC, and PLSR yield slightly different interpretations regarding the relationship between child psychopathology and brain volume. In demonstrating the divergence between these approaches, we exemplify the importance of carefully considering the method’s underlying assumptions when choosing a multivariate approach to delineate brain-behavior relationships

A genetically informed study of the associations between maternal age at childbearing and adverse perinatal outcomes

We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.NonePublishe

Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. © 2014 Michalska, Decety, Liu, Chen, Martz, Jacob, Hipwell, Lee, Chronis-Tuscano, Waldman and Lahey

Using confirmatory factor analysis to measure contemporaneous activation of defined neuronal networks in functional magnetic resonance imaging

a b s t r a c t a r t i c l e i n f o Functional neuroimaging often generates large amounts of data on regions of interest. Such data can be addressed effectively with a widely-used statistical technique based on measurement theory that has not yet been applied to neuroimaging. Confirmatory factor analysis is a convenient hypothesis-driven modeling environment that can be used to conduct formal statistical tests comparing alternative hypotheses regarding the elements of putative neuronal networks. In such models, measures of each activated region of interest are treated as indicators of an underlying latent construct that represents the contemporaneous activation of the elements in the network. As such, confirmatory factor analysis focuses analyses on the activation of hypothesized networks as a whole, improves statistical power by modeling measurement error, and provides a theory-based approach to data reduction with a robust statistical basis. This approach is illustrated using data on seven regions of interest in a hypothesized mesocorticostriatal reward system in a sample of 262 adult volunteers assessed during a card-guessing reward task. A latent construct reflecting contemporaneous activation of the reward system was found to be significantly associated with a latent construct measuring impulsivity, particularly in males