Associations Between Resting State Functional Connectivity and a Hierarchical Dimensional Structure of Psychopathology in Middle Childhood

Abstract

Background: Previous research from the Adolescent Brain Cognitive Development (ABCD) study delineated and validated a hierarchical 5-factor structure with a general psychopathology ('p') factor at the apex and five specific factors (internalizing, somatoform, detachment, neurodevelopmental, externalizing) using parent-reported child symptoms. The current study is the first examining associations between dimensions from a hierarchical structure and resting state functional connectivity (RSFC) networks.Methods: Using 9-11-year-old children from the ABCD baseline sample, we compared the variance explained by each hierarchy level (p-factor, 2-factor, 3-factor, 4-factor, and 5-factor models) in RSFC. Analyses were first conducted in a discovery dataset (n=3790) with significant associations examined in a replication dataset (n=3791). Results:The current study found associations between p-factor and lower connectivity within default mode network (DMN), although stronger effects emerged for the neurodevelopmental factor. Neurodevelopmental impairments were related to variation in RSFC networks associated with attention to internal states and external stimuli.These networks included within DMN, DMN with cingulo-opercular (CON) and 'Other' (Unassigned) networks, CON with ventral attention and 'Other' network, and dorsal attention with 'Other' network. Results held when accounting for parental psychopathology. Conclusion:The hierarchical structure of psychopathology showed replicable links to RSFC alterations in middle childhood. The p-factor had minimal association with altered connectivity, while the specific neurodevelopmental dimension showed robust Functional Connectivity and Dimensions of Psychopathology in Childhood 3 associations with multiple RSFC impairments. Results show the utility of examining associations between intrinsic brain architecture and specific dimensions of psychopathology, revealing associations specifically with neurodevelopmental impairments. Functional Connectivity and Dimensions of Psychopathology in Childhood 4The Research Domains Criteria (RDoC) 1,2 and Hierarchical Taxonomy of Psychopathology (HiTOP) 3,4 are transdiagnostic initiatives that have pushed psychiatric research to move beyond traditional diagnostic categories and to examine psychiatric problems as a multidimensional structure. One advantage of this approach is that dimensional constructs may align more closely to underlying neural mechanisms than diagnoses. 2,5 The HiTOP model proposes that dimensions of psychopathology are organized hierarchically, from narrowest to broadest, with each dimension potentially providing important information in terms of functional and biological correlates. 6 , 7Several dimensions of psychopathology have been identified in children and adolescents. [8][9][10][11] In particular, a study of the Child Behavioral Checklist (CBCL) 8 in Adolescent Brain Cognitive Development (ABCD) data found a hierarchical structure of psychopathology with a broad general "p-factor" at the apex, which progressively dif...

Is executive dysfunction a risk marker or consequence of psychopathology? A test of executive function as a prospective predictor and outcome of general psychopathology in the adolescent brain cognitive development study®

“…The current findings also are consistent with recent neuroimaging research, which has found structural and functional alterations in frontoparietal, default mode, visual association cortex, and cerebello-thalamo-cerebro-cortical neural circuits involved in executive control in those high in p ( Elliott et al, 2018 ; Karcher et al, 2020 ; Moberget et al, 2019 ; Romer et al, 2019 , 2018 ; Romer and Pizzagalli, 2021 ; Sato et al, 2016 ). An important next step will be to determine whether structural and functional alterations in these neural circuits prospectively predict future general psychopathology and whether those relations are mediated by executive dysfunction.…”

“…The hypothesis that poor EF may contribute to the p factor is supported by neuroimaging and genetics research as well. Specifically, structural and functional neural abnormalities in frontoparietal, default mode, visual association, and cerebello-thalamo-cerebro-cortical circuits involved in cognitive control have been identified in transdiagnostic meta-analyses ( Goodkind et al, 2015 ; McTeague et al, 2017 ; Sha et al, 2019 ; Shanmugan et al, 2016 ) and in studies of the neural correlates of the p factor ( Elliott et al, 2018 ; Karcher et al, 2020 ; Moberget et al, 2019 ; Romer et al, 2019 , 2018 ; Sato et al, 2016 ; Snyder et al, 2017 ). Shared genetic influences on EF, cognitive function, and transdiagnostic psychopathology in youth twins also has been identified ( Alnæs et al, 2018 ; Grotzinger et al, 2019 ; Harden et al, 2020 ).…”

Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth

“…Consistent with our findings, previous transdiagnostic studies have reported common disrupted patterns of functional connectivity across mental disorders (Baker et al, 2019; Barron et al, 2020; Ma et al, 2020; Qi et al, 2020; Xia et al, 2018). Moreover, recent studies have demonstrated that the overall psychopathology factor is associated with abnormalities of both within- and between-network functional connectivity (Elliott et al, 2018; Karcher et al, 2020; Kebets et al, 2019). However, these studies calculated functional connectivity by applying a group-level functional atlas to each individual.…”

“…Similarly, using functional MRI, trans-diagnostic studies have reported dysfunction of association networks across diagnoses (Sha et al, 2019), which may reflect neurobiological correlates of pervasive comorbid psychopathology. Supporting this notion, the burden of overall psychopathology has been linked to abnormal patterns of functional connectivity between large-scale cortical networks (Elliott et al, 2018;Karcher et al, 2020;Kaufmann et al, 2017;Kebets et al, 2019). Nonetheless, it remains unknown whether individual differences in functional topography are related to major dimensions of psychopathology in youth, or whether abnormalities of association cortex topography are linked to overall psychopathology across disorders.…”

Attenuated Resting-State Functional Anticorrelation between Attention and Executive Control Networks in Schizotypal Personality Disorder

“…Consequently, the altered communication between these components may have cascading, detrimental effects on the optimal dynamics of RSNs involved with various cognitive processes ranging from perceptual–attentional to higher-order mental processes. In particular, impaired anticorrelations between the DAN and other networks reflect disrupted functional integration, which may lead to neurodevelopmental problems [ 52 ].…”