The relationship between brain structure and general psychopathology in preadolescents

Abstract

Categorical mental disorders are being recognized as suboptimal targets in clinical neuroscience due to poor reliability as well as high rates of heterogeneity within, and comorbidity between, mental disorders. As an alternative to the case-control approach, recent studies have focused on the relationship between neurobiology and latent dimensions of psychopathology. The current study aimed to investigate the relationship between brain structure and psychopathology in the critical preadolescent period when psychopathology is emerging. This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,721; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, and parental education. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There was evidence of a relationship between externalizing psychopathology and frontal regions of the cortex that was independent of general psychopathology. The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. The widespread and pervasive relationships between general psychopathology and brain structure may reflect cognitive dysfunction that is a feature across a range of mental illnesses.

Specificity of cortical area and thickness as biomarkers for comorbid internalizing and externalizing mental disorders in pre-adolescence

“…Mental disorder diagnoses were determined using parent or guardian responses to the parent-reported computerized Schedule for Affective Disorders and Schizophrenia for School-Age Children for DSM-5 (K-SADS-5) (35). Lifetime (past or present) diagnoses of the 18 disorders were used (22, 36, 37). Based on the definition of broad diagnostic families adopted in recent studies (36, 38, 39), two broad diagnostic families including externalizing disorders (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct disorder), internalizing disorders (Dysthymia, Major Depressive Disorder, Disruptive Mood Dysregulation Disorder, Agoraphobia, Panic Disorder, Specific Phobia, Separation Anxiety Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post-Traumatic Stress Disorder) were used in our analysis (Figure 1A).…”

“…Mental disorder diagnoses were determined using parent or guardian responses to the parent-reported computerized Schedule for Affective Disorders and Schizophrenia for School-Age Children for DSM-5 (K-SADS-5) (35). Lifetime (past or present) diagnoses of the 18 disorders were used (22,36,37). Based on the definition of broad diagnostic families adopted in recent studies (36,38,39) were used in our analysis (Figure 1A).…”

“…A previous examination of the ABCD cohort found no association between general psychopathology (internalizing and externalizing symptoms) with CT. However, comorbidity was not specifically studied in this analysis (22). In contrast, SA was found to be correlated with general psychopathology.…”

General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study

“…Conceptual frameworks have suggested a bidirectional relationship between cognitive function and psychopathology ( Batty et al, 2005 ; Calvete et al, 2013 ; Schweizer and Hankin, 2018 ). With the advent of large-scale magnetic resonance imaging (MRI) studies, group differences in the structural properties of the cerebral cortex (predominantly cortical thickness) have been reported in common psychiatric disorders ( Ching et al, 2020 ; Hoogman et al, 2020 ; Thompson et al, 2020 ; Van den Heuvel et al, 2020 ; Patel et al, 2021 ), as well as in relation to general psychopathology ( Mewton et al, 2020 ; Romer et al, 2021a , b ) and cognitive ability ( Shaw et al, 2006 ; Karama et al, 2014 ).…”

Editorial: Transdiagnostic research: transitory or transformative?

“…Transdiagnostic research has also reached neuroscience, as demonstrated in the final two papers I focus on from this journal issue. Mewton et al (2022) reported on the relationship between general and specific psychopathology in preadolescents (9-10-year-olds) and brain structure measured using MRI in a community cohort study, the Adolescent Brain and Cognitive Development study. Their variables for general psychopathology as well as externalising, internalising and thought disorder 'lower order' dimensions were derived from a higher-order model of psychopathology using confirmatory factor analysis (for a discussion of the pfactor model of psychopathology, see elsewhere (Caspi & Moffitt, 2018;Ronald, 2019).…”