Minor physical anomalies: Modifiers of environmental risk for psychopathology

Tested the hypothesis that minor physical anomalies (MPAs) modify an adolescent\u27s vulnerability to environmental risk factors for psychopathology. 118 male 17-yr-olds who had been evaluated as 7-year-olds received a comprehensive neuropsychiatric evaluation. The evaluation included standardized assessments of environmental risk factors for psychiatric impairment, neurological signs, IQ, MPAs, and psychiatric impairment. The relationship between psychiatric status and environmental risk was examined as a function of the MPA profile. There was a significant interaction between MPAs and environmental risk in predicting psychiatric status. Environmental risk was more predictive of psychiatric impairment at age 17 in Ss with high scores on the MPA scale than in Ss with low scores on the scale. This relationship was particularly apparent in Ss with conduct disorder. MPAs also exhibited relationships with 2 childhood factors, neurological soft signs and Verbal IQ, that had been shown to predict adolescent psychopathology in prior reports on this cohort

Attention bias and anxiety in young children exposed to family violence

Background—Attention bias towards threat is associated with anxiety in older youth and adults and has been linked with violence exposure. Attention bias may moderate the relationship between violence exposure and anxiety in young children. Capitalizing on measurement advances, the current study examines these relationships at a younger age than previously possible. Methods—Young children (mean age 4.7, ±0.8) from a cross-sectional sample oversampled for violence exposure (N = 218) completed the dot-probe task to assess their attention biases. Observed fear/anxiety was characterized with a novel observational paradigm, the Anxiety Diagnostic Observation Schedule. Mother-reported symptoms were assessed with the Preschool-Age Psychiatric Assessment and Trauma Symptom Checklist for Young Children. Violence exposure was characterized with dimensional scores reflecting probability of membership in two classes derived via latent class analysis from the Conflict Tactics Scales: Abuse and Harsh Parenting. Results—Family violence predicted greater child anxiety and trauma symptoms. Attention bias moderated the relationship between violence and anxiety

Cortical and subcortical brain structure in generalized anxiety disorder : findings from 28 research sites in the ENIGMA-Anxiety Working Group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This megaanalysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

Age-Related Influence of Contingencies on a Saccade Task

Background: Adolescence is characterized by increased risk-taking and sensation seeking, presumably brought about by developmental changes within reward-mediating brain circuits. A better understanding of the neural mechanisms underlying reward-seeking during adolescence can have critical implications for the development of strategies to enhance adolescent performance in potentially dangerous situations. Yet little research has investigated the influence of age on the modulation of behavior by incentives with neuroscience-based methods Methods: A monetary reward antisaccade task (the RST) was used with 23 healthy adolescents and 30 healthy adults. Performance accuracy, latency and peak velocity of saccade responses (prosaccades and antisaccades) were analyzed. Results: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment) for both, prosaccades and antisaccades. However, modulation of antisaccade errors (direction errors) by incentives differed between groups: adolescents modulated saccade latency and peak velocity depending on contingencies, with incentives aligning their performance to that of adults; adults did not show a modulation by incentives. Conclusions: These findings suggest that incentives modulate a global measure of performance (percent direction errors) in adults and adolescents, and exert a more powerful influence on the control of incorrect motor responses in adolescents than in adults. These findings suggest that this task can be used in neuroimaging studies as a probe of the influence of incentives on cognitive control from a developmental perspective as well as in health and disease

Probing the Neural Correlates of Anticipated Peer Evaluation in Adolescence

Neural correlates of social cognition were assessed in 9-to-17-year-olds using functional magnetic resonance imaging (fMRI). Participants appraised how unfamiliar peers they had previously identified as being of high or low interest would evaluate them for an anticipated online chat session. Differential age- and sex-related activation patterns emerged in several regions previously implicated in affective processing. These included the ventral striatum, hippocampus, hypothalamus, and insula. In general, activation patterns shifted with age in older relative to younger females, but showed no association with age in males. Relating these neural response patterns to changes in adolescent social-cognition enriches theories of adolescent social development through enhanced neurobiological understanding of social behavior

Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing

Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared to non-abused adolescents, although most prior research is based on adults and volume-based measures. The current study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence

Linked networks for learning and expressing location-specific threat

Learning locations of danger within our environment is a vital adaptive ability whose neural bases are only partially understood. We examined fMRI brain activity while participants navigated a virtual environment in which flowers appeared and were “picked.” Picking flowers in the danger zone (one-half of the environment) predicted an electric shock to the wrist (or “bee sting”); flowers in the safe zone never predicted shock; and household objects served as controls for neutral spatial memory. Participants demonstrated learning with shock expectancy ratings and skin conductance increases for flowers in the danger zone. Patterns of brain activity shifted between overlapping networks during different task stages. Learning about environmental threats, during flower approach in either zone, engaged the anterior hippocampus, amygdala, and ventromedial prefrontal cortex (vmPFC), with vmPFC–hippocampal functional connectivity increasing with experience. Threat appraisal, during approach in the danger zone, engaged the insula and dorsal anterior cingulate (dACC), with insula–hippocampal functional connectivity. During imminent threat, after picking a flower, this pattern was supplemented by activity in periaqueductal gray (PAG), insula–dACC coupling, and posterior hippocampal activity that increased with experience. We interpret these patterns in terms of multiple representations of spatial context (anterior hippocampus); specific locations (posterior hippocampus); stimuli (amygdala); value (vmPFC); threat, both visceral (insula) and cognitive (dACC); and defensive behaviors (PAG), interacting in different combinations to perform the functions required at each task stage. Our findings illuminate how we learn about location-specific threats and suggest how they might break down into overgeneralization or hypervigilance in anxiety disorders

Neural Correlates of Treatment in Adolescents with Generalized Anxiety Disorder: A Preliminary Investigation

Objective: Generalized anxiety disorder (GAD) is a prevalent and debilitating psychiatric condition in adolescence. Two effective forms of treatment are cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors. This pilot study examined changes in brain function following each type of treatment in GAD. Method: Subjects were 14 youth with GAD (7 had CBT, 7 received fluoxetine) and 10 age- and gender-matched healthy peers. FMRI scans were acquired before and after treatment for patients, and over two comparable time points for controls. During fMRI acquisition, a probe detection task with emotional (angry, happy) and neutral faces allowed for assessment of neural response to threat. Following previous research, region of interest analyses were performed in the right ventrolateral prefrontal cortex (VLPFC). Results: FMRI results showed increased VLPFC activation, relative to controls, in the medication (t(15) = 3.01, p \u3c 0.01) and CBT (t(15) = 3.22, p \u3c 0.01) groups following treatment. Conclusions: This study shows significant increase in VLPFC activation in response to angry faces following treatment with CBT or fluoxetine for GAD. This is consistent with previous research indicating that the VLPFC may facilitate effective responding to underlying neural correlates of anxiety in other brain regions, such as the amygdala

Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and 12 age-, gender- and IQ-matched, psychiatrically-healthy adolescents received ‘not interested’ and ‘interested’ feedback from unknown peers during a Chatroom task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high desirability ratings. Further highlighting the salience of such feedback, all adolescents, independent of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety

Robust caregiver-youth discrepancies in irritability ratings on the affective reactivity index: An investigation of its origins

OBJECTIVE: The Affective Reactivity Index (ARI) is widely used to assess young people's irritability symptoms, but youth and caregivers often diverge in their assessments. Such informant discrepancy might be rooted in poor psychometric properties, the differential conceptualization of irritability across informants, or reflect sociodemographic and clinical characteristics. We use an out-of-sample replication approach and leverage longitudinal data, available for a subset of the participants, to test these hypotheses. METHOD: Across two independent samples (NCohort-1 = 765, 8-21 years; NCohort-2 = 1910, 6-21 years), we investigate the reliability and measurement invariance of the ARI, examine sociodemographic and clinical predictors of discrepant reporting and probe the utility of a bifactor model for cross-informant integration. RESULTS: Despite good internal consistency and 6-week-retest-reliability of parent (Cohort-1: α = 0.92, ICC = 0.85; Cohort-2: α = 0.93) and youth forms (Cohort-1: α = 0.88, ICC = 0.78; Cohort-2: α = 0.82), we confirm substantial informant discrepancy in ARI ratings (3 points on a scale from 0 to 12), which is stable over six weeks (ICC = 0.53). Measurement invariance across informants was weak, indicating that parents and youth may interpret ARI items differently. Irritability severity and diagnostic status predicted informant-discrepancy, albeit in opposing directions: higher severity was linked to relative, higher irritability-ratings by youth (Cohort-1: β = -0.06, p < .001; Cohort-2: β = -0.06, p < .001), while diagnoses of Disruptive Mood Dysregulation Disorder (Cohort-1: β = 0.44, p < .001; Cohort-2: β = 0.84, p < .001) and Oppositional Defiant Disorder (Cohort-1: β = 0.41, p < .001; Cohort-2: β = 0.42, p < .001) predicted relative higher irritability-ratings by caregivers. In both datasets, a bifactor model parsing informant-specific from shared irritability-related variance fit the data well (CFI = 0.99, RMSEA = 0.05; N2: CFI = 0.99; RMSEA = 0.04). CONCLUSION: Parent and youth ARI reports and their discrepancy are reliable and reflect different interpretations of the scale items; hence they should not be averaged. This finding also suggests that irritability is not a unitary construct. Future work should investigate and model how different aspects of irritability might differ in their impact on the responses of specific informants