Gray matter volume associations in youth with ADHD features of inattention and hyperactivity/impulsivity.

BACKGROUND: Prior research has shown smaller cortical and subcortical gray matter volumes among individuals with attention-deficit/hyperactivity disorder (ADHD). However, neuroimaging studies often do not differentiate between inattention and hyperactivity/impulsivity, which are distinct core features of ADHD. The present study uses an approach to disentangle overlapping variance to examine the neurostructural heterogeneity of inattention and hyperactivity/impulsivity dimensions. METHODS: We analyzed data from 10,692 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study. Confirmatory factor analysis was used to derive factors representing inattentive and hyperactive/impulsive traits. We employed structural equation modeling to examine these factors' associations with gray matter volume while controlling for the shared variance between factors. RESULTS: Greater endorsement of inattentive traits was associated with smaller bilateral caudal anterior cingulate and left parahippocampal volumes. Greater endorsement of hyperactivity/impulsivity traits was associated with smaller bilateral caudate and left parahippocampal volumes. The results were similar when accounting for socioeconomic status, medication, and in-scanner motion. The magnitude of these findings increased when accounting for overall volume and intracranial volume, supporting a focal effect in our results. CONCLUSIONS: Inattentive and hyperactivity/impulsivity traits show common volume deficits in regions associated with visuospatial processing and memory while at the same time showing dissociable differences, with inattention showing differences in areas associated with attention and emotion regulation and hyperactivity/impulsivity associated with volume differences in motor activity regions. Uncovering such biological underpinnings within the broader disorder of ADHD allows us to refine our understanding of ADHD presentations.

Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.

The effects of induced and trait anxiety on the sequential modulation of emotional conflict.

The current study aimed to investigate whether induced anxiety, as well as trait anxiety, would lead to the failure of the regulation of emotional conflict. To measure the regulation of emotional conflict, the congruency sequence effect (CSE), which is a reduced effect of task-irrelevant distractor after incongruent trials compared to congruent trials, was observed while participants performed an emotional conflict task. In Experiment 1, participants performed the task in a safe context and a threatening context where a couple of electric shocks were given randomly on two consecutive days. In Experiment 2, participants performed the same task in either a safe or threatening context to avoid a potential carryover effect of the threat. The CSE observed in the safe context disappeared in the threatening context as well as in participants with high-trait anxiety level even without the threat. The findings imply that induced anxiety causes a failure of cognitive control that engenders the CSE in emotional congruency tasks. Moreover, such failure driven by participants' trait anxiety level might be a potential predisposing factor leading to anxiety disorders. Overall, these results suggest that induced anxiety, as well as trait anxiety, has an adverse impact on the sequential modulation of emotional conflict.

Early life stress and functional network topology in children.

Brain networks are continuously modified throughout development, yet this plasticity can also make functional networks vulnerable to early life stress. Little is currently known about the effect of early life stress on the functional organization of the brain. The current study investigated the association between environmental stressors and network topology using data from the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study. Hierarchical modeling identified a general factor of environmental stress, representing the common variance across multiple stressors, as well as four subfactors including familial dynamics, interpersonal support, neighborhood SES deprivation, and urbanicity. Functional network topology metrics were obtained using graph theory at rest and during tasks of reward processing, inhibition, and affective working memory. The general factor of environmental stress was associated with less specialization of networks, represented by lower modularity at rest. Local metrics indicated that general environmental stress was also associated with less efficiency in the subcortical-cerebellar and visual networks while showing greater efficiency in the default mode network at rest. Subfactors of environmental stress were associated with differences in specialization and efficiency in select networks. The current study illustrates that a wide range of stressors in a child's environment are associated with differences in brain network topology.

Atypical Functional Network Properties and Associated Dimensions of Child Psychopathology During Rest and Task Performance.

Background: When brain networks deviate from typical development, this is thought to contribute to varying forms of psychopathology. However, research has been limited by the reliance on discrete diagnostic categories that overlook the potential for psychological comorbidity and the dimensional nature of symptoms. Methods: This study examined the topology of functional networks in association with 4 bifactor-defined psychopathology dimensions-general psychopathology, internalizing symptoms, conduct problems, and attention-deficit/hyperactivity disorder symptoms-via the Child Behavior Checklist in a sample of 3568 children from the ABCD (Adolescent Brain Cognitive Development) Study. Local and global graph theory metrics were calculated at rest and during tasks of reward processing, inhibition, and working memory. Results: Greater attention-deficit/hyperactivity disorder symptoms were associated with reduced modularity across rest and tasks as well as reduced local efficiency in motor networks at rest. Results survived sensitivity analyses for medication and socioeconomic status. Greater conduct problem symptoms were associated with reduced modularity on working memory and reward processing tasks; however, these results did not persist after sensitivity analyses. General psychopathology and internalizing symptoms showed no significant network associations. Conclusions: Our findings suggest reduced efficiency in topology in those with greater attention-deficit/hyperactivity disorder symptoms across 4 critical cognitive states, with conduct problems also showing network deficits, although less consistently. This may suggest that modularity deficits are a neurobiological marker of externalizing behavior in children. Such specificity has not been demonstrated before using graph theory metrics and has the potential to redefine our understanding of network deficits in children with psychopathology symptoms.

General and Specific Factors of Environmental Stress and Their Associations With Brain Structure and Dimensions of Psychopathology.

Background: Early-life stressors can adversely affect the developing brain. While hierarchical modeling has established the existence of a general factor of psychopathology, no studies have modeled a general factor of environmental stress and related this factor to brain development. Using a large sample of children from the ABCD (Adolescent Brain Cognitive Development) Study, the current study aimed to identify general and specific factors of environmental stress and test their associations with brain structure and psychopathology. Methods: In a sample of 11,878 children, bifactor modeling and higher-order (second-order) modeling identified general and specific factors of environmental stress: family dynamics, interpersonal support, neighborhood socioeconomic status deprivation, and urbanicity. Structural equation modeling was performed to examine associations between these factors and regional gray matter volume (GMV) and cortical thickness as well as general and specific factors of psychopathology. Results: The general environmental stress factor was associated with globally smaller cortical and subcortical GMV as well as thinner cortices across widespread regions. Family dynamics and neighborhood socioeconomic status deprivation were associated with smaller GMV in focal regions. Urbanicity was associated with larger cortical and subcortical GMV and thicker cortices in frontotemporal regions. The environmental factors were associated with psychopathology in the expected directions. The general factors of environmental stress and psychopathology were both predictors of smaller GMV in children, while remaining distinct from each other. Conclusions: This study reveals a unifying model of environmental influences that illustrates the inherent organization of environmental stressors and their relationship to brain structure and psychopathology.

Multivariate analytical approaches for investigating brain-behavior relationships.

Background: Many 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. Method: We 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. Results: The 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. Conclusion: Here 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.

Differentiating stages of reward responsiveness: Neurophysiological measures and associations with facets of the behavioral activation system.

The Research Domain Criteria (RDoC) positive valence systems domain include multiple aspects of reward responsiveness with potential to elucidate the understanding of motivational and hedonic deficits in psychological disorders. There is a need for reliable and valid methods to delineate behavioral and biological processes underlying stages of reward responsiveness. Event-related potentials (ERPs) offer a promising method for examining the temporal dynamics of reward processing, but the literature has mainly focused on the feedback stage and often single components. We investigated the electrophysiological aspects of reward anticipation and initial response to reward using an ERP monetary incentive delay task in 114 emerging adults. Principal component analysis was used to derive temporally and spatially distinct ERP components sensitive to reward processing. Components that reflect initial engagement toward a cue indicating potential reward (cue-P3) and anticipation of possible reward feedback (stimulus-preceding negativity; SPN) emerged in the anticipatory stage. In the initial response to reward stage, a reward positivity (RewP) was found. We further tested the association between ERPs and self-reported facets of the behavioral activation system. Greater self-reported reward responsiveness was associated with heightened response in the anticipatory stage (i.e., cue-P3, SPN). Self-reported drive was positively associated with RewP, but fun-seeking was negatively associated with RewP. Additional components were observed beyond those identified in prior work, warranting future research on temporal dynamics of reward processing across stages. Furthermore, examination of a broader range of reward-related ERPs in clinical populations has the potential to more precisely characterize alterations in positive valence systems in psychopathology.

Association of gray matter volumes with general and specific dimensions of psychopathology in children.

Childhood is an important time for the manifestation of psychopathology. Psychopathology is characterized by considerable comorbidity which is mirrored in the underlying neural correlates of psychopathology. Both common and dissociable variations in brain volume have been found across multiple mental disorders in adult and youth samples. However, the majority of these studies used samples with broad age ranges which may obscure developmental differences. The current study examines associations between regional gray matter volumes (GMV) and psychopathology in a large sample of children with a narrowly defined age range. We used data from 9607 children 9-10 years of age collected as part of the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A bifactor model identified a general psychopathology factor that reflects common variance across disorders and specific factors representing internalizing symptoms, ADHD symptoms, and conduct problems. Brain volume was acquired using 3T MRI. After correction for multiple testing, structural equation modeling revealed nearly global inverse associations between regional GMVs and general psychopathology and conduct problems, with associations also found for ADHD symptoms (pfdr-values ≤ 0.048). Age, sex, and race were included as covariates. Sensitivity analyses including total GMV or intracranial volume (ICV) as covariates support this global association, as a large majority of region-specific results became nonsignificant. Sensitivity analyses including income, parental education, and medication use as additional covariates demonstrate largely convergent results. These findings suggest that globally smaller GMVs are a nonspecific risk factor for general psychopathology, and possibly for conduct problems and ADHD as well.

The association between latent trauma and brain structure in children.

The developing brain is marked by high plasticity, which can lead to vulnerability to early life stressors. Previous studies indicate that childhood maltreatment is associated with structural aberrations across a number of brain regions. However, prior work is limited by small sample sizes, heterogeneous age groups, the examination of one structure in isolation, the confounding of different types of early life stressors, and not accounting for socioeconomic status. These limitations may contribute to high variability across studies. The present study aimed to investigate how trauma is specifically associated with cortical thickness and gray matter volume (GMV) differences by leveraging a large sample of children (N = 9270) from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A latent measure of trauma exposure was derived from DSM-5 traumatic events, and we related this measure of trauma to the brain using structural equation modeling. Trauma exposure was associated with thinner cortices in the bilateral superior frontal gyri and right caudal middle frontal gyrus (pfdr-values < .001) as well as thicker cortices in the left isthmus cingulate and posterior cingulate (pfdr-values ≤ .027), after controlling age, sex, and race/ethnicity. Furthermore, trauma exposure was associated with smaller GMV in the right amygdala and right putamen (pfdr-values ≤ .048). Sensitivity analyses that controlled for income and parental education were largely consistent with the main findings for cortical thickness. These results suggest that trauma may be an important risk factor for structural aberrations, specifically for cortical thickness differences in frontal and cingulate regions in children.

Criterion validity and relationships between alternative hierarchical dimensional models of general and specific psychopathology.

[Correction Notice: An Erratum for this article was reported in Vol 129(7) of Journal of Abnormal Psychology (see record 2020-72912-001). In the article (http://dx.doi.org/10.1037/abn0000601), an acknowledgment is missing from the author note. The missing acknowledgement is included in the erratum.] Psychopathology can be viewed as a hierarchy of correlated dimensions. Many studies have supported this conceptualization, but they have used alternative statistical models with differing interpretations. In bifactor models, every symptom loads on both the general factor and 1 specific factor (e.g., internalizing), which partitions the total explained variance in each symptom between these orthogonal factors. In second-order models, symptoms load on one of several correlated lower-order factors. These lower-order factors load on a second-order general factor, which is defined by the variance shared by the lower-order factors. Thus, the factors in second-order models are not orthogonal. Choosing between these valid statistical models depends on the hypothesis being tested. Because bifactor models define orthogonal phenotypes with distinct sources of variance, they are optimal for studies of shared and unique associations of the dimensions of psychopathology with external variables putatively relevant to etiology and mechanisms. Concerns have been raised, however, about the reliability of the orthogonal specific factors in bifactor models. We evaluated this concern using parent symptom ratings of 9-10 year olds in the ABCD Study. Psychometric indices indicated that all factors in both bifactor and second-order models exhibited at least adequate construct reliability and estimated replicability. The factors defined in bifactor and second-order models were highly to moderately correlated across models, but have different interpretations. All factors in both models demonstrated significant associations with external criterion variables of theoretical and clinical importance, but the interpretation of such associations in second-order models was ambiguous due to shared variance among factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Correction to Moore et al. (2020).

Reports an error in "Criterion validity and relationships between alternative hierarchical dimensional models of general and specific psychopathology" by Tyler M. Moore, Antonia N. Kaczkurkin, E. Leighton Durham, Hee Jung Jeong, Malerie G. McDowell, Randolph M. Dupont, Brooks Applegate, Jennifer L. Tackett, Carlos Cardenas-Iniguez, Omid Kardan, Gaby N. Akcelik, Andrew J. Stier, Monica D. Rosenberg, Donald Hedeker, Marc G. Berman and Benjamin B. Lahey (Journal of Abnormal Psychology, Advanced Online Publication, Jul 16, 2020, np). In the article (http://dx.doi.org/10.1037/abn0000601), an acknowledgment is missing from the author note. The missing acknowledgement is included in the erratum. (The following abstract of the original article appeared in record 2020-50590-001.) Psychopathology can be viewed as a hierarchy of correlated dimensions. Many studies have supported this conceptualization, but they have used alternative statistical models with differing interpretations. In bifactor models, every symptom loads on both the general factor and 1 specific factor (e.g., internalizing), which partitions the total explained variance in each symptom between these orthogonal factors. In second-order models, symptoms load on one of several correlated lower-order factors. These lower-order factors load on a second-order general factor, which is defined by the variance shared by the lower-order factors. Thus, the factors in second-order models are not orthogonal. Choosing between these valid statistical models depends on the hypothesis being tested. Because bifactor models define orthogonal phenotypes with distinct sources of variance, they are optimal for studies of shared and unique associations of the dimensions of psychopathology with external variables putatively relevant to etiology and mechanisms. Concerns have been raised, however, about the reliability of the orthogonal specific factors in bifactor models. We evaluated this concern using parent symptom ratings of 9-10 year olds in the ABCD Study. Psychometric indices indicated that all factors in both bifactor and second-order models exhibited at least adequate construct reliability and estimated replicability. The factors defined in bifactor and second-order models were highly to moderately correlated across models, but have different interpretations. All factors in both models demonstrated significant associations with external criterion variables of theoretical and clinical importance, but the interpretation of such associations in second-order models was ambiguous due to shared variance among factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).