Implications of the Hierarchical Structure of Psychopathology for Psychiatric Neuroimaging

Abstract

Research into the neurobiological substrates of psychopathology has been impeded by heterogeneity within diagnostic categories, comorbidity among mental disorders, and the presence of symptoms that transcend diagnostic categories. Solutions to these issues increasingly focus neurobiological research on isolated or narrow groupings of symptoms or functional constructs rather than categorical diagnoses. Here we argue for a more integrative approach that also incorporates the broad hierarchical structure of psychopathological symptoms and their etiological mechanisms. This approach places clinical neuroscience research in the context of a hierarchy of empirically defined factors of symptoms such as internalizing disorders, externalizing disorders, and the general factor of psychopathology. Application of this hierarchical approach has the potential to reveal neural substrates that nonspecifically contribute to multiple forms of psychopathology and their comorbidity, and in doing so, facilitate the study of mechanisms that are specific to single dimensions and subsets of symptoms. Neurobiological research on the hierarchy of dimensions of psychopathology is only just beginning to emerge, but has the potential to radically alter our understanding of the neurobiology of abnormal behavior.

Keywords: Comorbidity; Externalizing; Internalizing; Research Domain Criteria; Transdiagnostic; fMRI.

Fig 1

A) Histograms of polychoric correlations among psychopathology symptoms based on caretaker interview with the Child and Adolescent Psychopathology Scale (74) for adolescents in Wave 1 of the Tennessee Twin Study (TTS) (16). Although there is variability in the magnitudes of correlations, most symptoms show at least modest positive correlations with a broad array of other symptoms. Note: a small number of items with correlations +/- than 4 s.d. below the mean were excluded. In each case these involved items with extremely low endorsement rates. B) Correlations among first-order latent dimensions of psychopathology in wave 1 of the TTS based on the same symptoms. The figure is redrawn from Figure 5 page 196 (16). Note: only correlations greater than r = .40 are shown, but all additional correlations are statistically significant. Abbreviations: ODD = oppositional defiant disorder; CD = conduct disorder; HI = hyperactivity-impulsivity; INATT = inattention; MDD = major depressive disorder; GAD = generalized anxiety disorder; social = social phobia; SAD = separation anxiety disorder; spec = specific phobia; agora = agoraphobia.

Fig 2

Best fitting models of the correlational structure of 11 categorical mental disorders in confirmatory factor analyses of diagnosis data from wave 1 of the NESARC sample. (A) The 3-factor model in which the second-order internalizing factor splits into distinct distress and fears factors fits the data well, but it includes significant positive correlations among the distress, fears and externalizing second-order factors. (B) The bifactor model with a general psychopathology factor that is associated directly with each disorder further improves the fit. Adapted from Figure 1, page 973 (5).