Distinct Patterns of Reduced Prefrontal and Limbic Gray Matter Volume in Childhood General and Internalizing Psychopathology

Abstract

Reduced grey matter volume (GMV) is widely implicated in psychopathology, but studies have found mostly overlapping areas of GMV reduction across disorders rather than unique neural signatures, potentially due to pervasive comorbidity. GMV reductions may be associated with broader psychopathology dimensions rather than specific disorders. We used an empirically supported bifactor model consisting of common psychopathology and internalizing- and externalizing-specific factors to evaluate whether latent psychopathology dimensions yield a clearer, more parsimonious pattern of GMV reduction in prefrontal and limbic/paralimbic areas implicated in individual disorders. A community sample of children (n=254, ages 6–10) was used to to evaluate whether GMV reductions could constitute early neural risk factors. The common psychopathology factor was associated with reduced GMV in prefrontal areas (dorsal, orbitofrontal, ventrolateral). The internalizing-specific factor was related to reduced GMV in limbic/paralimbic areas (hippocampus, amygdala, insula). No significant associations were found between GMV and the externalizing-specific factor after accounting for common psychopathology.

Developmental Patterning of Irritability Enhances Prediction of Psychopathology in Pre-adolescence: Improving RDoC with Developmental Science

“…In contrast, the current study examined the normal:abnormal spectrum of irritability longitudinally. The current findings are also consistent with extant studies that link adolescent internalizing and externalizing symptoms to variation in brain structure (Andre et al, 2019;Goodkind et al, 2015;Kaczkurkin, Park, et al, 2019;Pagliaccio et al, 2018;Snyder et al, 2017). This literature suggests that general psychopathology is related to variation in amygdala (Andre et al, 2019;Goodkind et al, 2015;Snyder et al, 2017), hippocampal (Andre et al, 2019;Goodkind et al, 2015;Snyder et al, 2017), temporal regions (Pagliaccio et al, 2018;Snyder et al, 2017), and ventral frontal regions (Pagliaccio et al, 2018;Snyder et al, 2017) which, in the current study, had the largest association with school age irritability.…”

Appropriate Use of Bifactor Analysis in Psychopathology Research: Appreciating Benefits and Limitations

“…with important antecedents, biological substrates, or outcomes, this supports its interpretation as a meaningful construct; the p-factor shows genetic correlations with Neuroticism (12) and reduced gray matter volume in prefrontal areas (19).…”

“…A growing area of research examines biological substrates of psychological constructs, such as neurobiological and genetic correlates of individual differences in personality, cognition, or psychopathology (102)(103)(104)(105). For example, several studies have examined or proposed correlations of psychopathology general and group factors with genetic singlenucleotide-polymorphisms or neurobiological variables (e.g., gray matter volume; volume or activation of amygdala/PFC circuits, HPA axis, hippocampus, ventral striatum) (19,(106)(107)(108)(109). These questions may benefit from bifactor models' utility for examining external variable relations.…”

“…The bifactor model has become popular in psychology and psychiatry research as a method to (a) model commonality and uniqueness across mental disorders and (b) relate said common and unique factors to putative antecedents (e.g., treatments, genetic/environmental factors, neurobiological substrates, personality traits) and outcomes (e.g., cognitive development, academic performance, distress, self-harm, suicidality) (11)(12)(13)(14)(15)(16)(17). Many studies have applied bifactor models to document a 'general psychopathology' or p-factor reflecting commonality among all forms of psychopathology, along with several narrower psychopathology group factors, most commonly internalizing (depression, anxiety) 3 , externalizing (antisocial and substance use disorders), and psychosis (7,11,14,(19)(20)(21)(22). Bifactor and related hierarchical models of psychopathology (23) are being incorporated in emerging frameworks for conceptualizing, studying, and diagnosing psychopathology (21,24).…”

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

“…In healthy individuals, the neural substrate of the p ‐factor appears to encompass a distributed network of brain structures. Volumetric studies implicate grey matter reductions in prefrontal (Snyder, Hankin, Sandman, Head, & Davis, ), striatal (Gong et al, ), occipital and cerebellar regions (Moberget et al, ; Romer et al, ) in association with greater expression of p . In terms of white matter integrity, commonly indexed using diffusion imaging metrics, reduced integrity in callosal (Riem et al, ) and pontine‐cerebellar (Romer et al, ) pathways are also linked to the expression of a p ‐factor.…”