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.
Project description:Neurobiological abnormalities associated with psychiatric disorders do not map well to existing diagnostic categories. High co-morbidity suggests dimensional circuit-level abnormalities that cross diagnoses. Here we seek to identify brain-based dimensions of psychopathology using sparse canonical correlation analysis in a sample of 663 youths. This analysis reveals correlated patterns of functional connectivity and psychiatric symptoms. We find that four dimensions of psychopathology - mood, psychosis, fear, and externalizing behavior - are associated (r?=?0.68-0.71) with distinct patterns of connectivity. Loss of network segregation between the default mode network and executive networks emerges as a common feature across all dimensions. Connectivity linked to mood and psychosis becomes more prominent with development, and sex differences are present for connectivity related to mood and fear. Critically, findings largely replicate in an independent dataset (n?=?336). These results delineate connectivity-guided dimensions of psychopathology that cross clinical diagnostic categories, which could serve as a foundation for developing network-based biomarkers in psychiatry.
Project description:BACKGROUND:A large body of research has focused on identifying the optimal number of dimensions - or spectra - to model individual differences in psychopathology. Recently, it has become increasingly clear that ostensibly competing models with varying numbers of spectra can be synthesized in empirically derived hierarchical structures. METHODS AND MATERIALS:We examined the convergence between top-down (bass-ackwards or sequential principal components analysis) and bottom-up (hierarchical agglomerative cluster analysis) statistical methods for elucidating hierarchies to explicate the joint hierarchical structure of clinical and personality disorders. Analyses examined 24 clinical and personality disorders based on semi-structured clinical interviews in an outpatient psychiatric sample (n=2900). RESULTS:The two methods of hierarchical analysis converged on a three-tier joint hierarchy of psychopathology. At the lowest tier, there were seven spectra - disinhibition, antagonism, core thought disorder, detachment, core internalizing, somatoform, and compulsivity - that emerged in both methods. These spectra were nested under the same three higher-order superspectra in both methods: externalizing, broad thought dysfunction, and broad internalizing. In turn, these three superspectra were nested under a single general psychopathology spectrum, which represented the top tier of the hierarchical structure. CONCLUSIONS:The hierarchical structure mirrors and extends upon past research, with the inclusion of a novel compulsivity spectrum, and the finding that psychopathology is organized in three superordinate domains. This hierarchy can thus be used as a flexible and integrative framework to facilitate psychopathology research with varying levels of specificity (i.e., focusing on the optimal level of detailed information, rather than the optimal number of factors).
Project description:Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Project description:The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1042 youths (ages 11-23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. CBF at rest was quantified on a voxelwise basis using arterial spin labeled perfusion MRI at 3T. A dimensional measure of psychopathology was constructed using a bifactor model of item-level data from a psychiatric screening interview, which delineated four factors (fear, anxious-misery, psychosis and behavioral symptoms) plus a general factor: overall psychopathology. Overall psychopathology was associated with elevated perfusion in several regions including the right dorsal anterior cingulate cortex (ACC) and left rostral ACC. Furthermore, several clusters were associated with specific dimensions of psychopathology. Psychosis symptoms were related to reduced perfusion in the left frontal operculum and insula, whereas fear symptoms were associated with less perfusion in the right occipital/fusiform gyrus and left subgenual ACC. Follow-up functional connectivity analyses using resting-state functional MRI collected in the same participants revealed that overall psychopathology was associated with decreased connectivity between the dorsal ACC and bilateral caudate. Together, the results of this study demonstrate common and dissociable CBF abnormalities across neuropsychiatric disorders in youth.
Project description:Hierarchical dimensional systems of psychopathology promise more informative descriptions for understanding risk and predicting outcome than traditional diagnostic systems, but it is unclear how many major dimensions they should include. We delineated the hierarchy of childhood and adult psychopathology and validated it against clinically relevant measures. Participants were 9987 9- and 10-year-old children and their parents from the Adolescent Brain Cognitive Development (ABCD) study. Factor analyses of items from the Child Behavior Checklist and Adult Self-Report were run to delineate hierarchies of dimensions. We examined the familial aggregation of the psychopathology dimensions, and the ability of different factor solutions to account for risk factors, real-world functioning, cognitive functioning, and physical and mental health service utilization. A hierarchical structure with a general psychopathology ('p') factor at the apex and five specific factors (internalizing, somatoform, detachment, neurodevelopmental, and externalizing) emerged in children. Five similar dimensions emerged also in the parents. Child and parent p-factors correlated highly (r = 0.61, p < 0.001), and smaller but significant correlations emerged for convergent dimensions between parents and children after controlling for p-factors (r = 0.09-0.21, p < 0.001). A model with child p-factor alone explained mental health service utilization (R2 = 0.23, p < 0.001), but up to five dimensions provided incremental validity to account for developmental risk and current functioning in children (R2 = 0.03-0.19, p < 0.001). In this first investigation comprehensively mapping the psychopathology hierarchy in children and adults, we delineated a hierarchy of higher-order dimensions associated with a range of clinically relevant validators. These findings hold important implications for psychiatric nosology and future research in this sample.
Project description:A multidimensional trait system has been proposed for representing personality disorder (PD) features in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to address problematic classification issues such as comorbidity. In this model, which may also assist in providing scaffolding for the underlying structure of major forms of psychopathology more generally, 25 primary traits are organized by 5 higher order dimensions: Negative Affect, Detachment, Antagonism, Disinhibition, and Psychoticism. We examined (a) the generalizability of the structure proposed for DSM-5 PD traits, and (b) the potential for an integrative hierarchy based upon DSM-5 PD traits to represent the dimensions scaffolding psychopathology more generally. A large sample of student participants (N = 2,461) completed the Personality Inventory for DSM-5, which operationalizes the DSM-5 traits. Exploratory factor analysis replicated the initially reported 5-factor structure, as indicated by high factor congruencies. The 2-, 3-, and 4-factor solutions estimated in the hierarchy of the DSM-5 traits bear close resemblance to existing models of common mental disorders, temperament, and personality pathology. Thus, beyond the description of individual differences in personality disorder, the trait dimensions might provide a framework for the metastructure of psychopathology in the DSM-5 and the integration of a number of ostensibly competing models of personality trait covariation.
Project description:OBJECTIVE:Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present. METHOD:The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). The effect of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) was examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses. RESULTS:Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo-opercular control network, including the frontal pole, cingulate cortex, and anterior insula. In addition, psychosis-spectrum symptoms were associated with hypoactivation of the left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypoactivation of the frontoparietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyperactivation of the executive network. CONCLUSIONS:These findings provide novel evidence that common and dissociable deficits within the brain's executive system are present in association with dimensions of psychopathology in youth.
Project description:The primary aim of this commentary is to describe trauma-related dissociation and altered states of consciousness in the context of a four-dimensional model that has recently been proposed (Frewen & Lanius, 2015). This model categorizes symptoms of trauma-related psychopathology into (1) those that occur within normal waking consciousness and (2) those that are dissociative and are associated with trauma-related altered states of consciousness (TRASC) along four dimensions: (1) time; (2) thought; (3) body; and (4) emotion. Clinical applications and future research directions relevant to each dimension are discussed. Conceptualizing TRASC across the dimensions of time, thought, body, and emotion has transdiagnostic implications for trauma-related disorders described in both the Diagnostic Statistical Manual and the International Classifications of Diseases. The four-dimensional model provides a framework, guided by existing models of dissociation, for future research examining the phenomenological, neurobiological, and physiological underpinnings of trauma-related dissociation.
Project description:We propose a taxonomy of psychopathology based on patterns of shared causal influences identified in a review of multivariate behavior genetic studies that distinguish genetic and environmental influences that are either common to multiple dimensions of psychopathology or unique to each dimension. At the phenotypic level, first-order dimensions are defined by correlations among symptoms; correlations among first-order dimensions similarly define higher-order domains (e.g., internalizing or externalizing psychopathology). We hypothesize that the robust phenotypic correlations among first-order dimensions reflect a hierarchy of increasingly specific etiologic influences. Some nonspecific etiologic factors increase risk for all first-order dimensions of psychopathology to varying degrees through a general factor of psychopathology. Other nonspecific etiologic factors increase risk only for all first-order dimensions within a more specific higher-order domain. Furthermore, each first-order dimension has its own unique causal influences. Genetic and environmental influences common to family members tend to be nonspecific, whereas environmental influences unique to each individual are more dimension-specific. We posit that these causal influences on psychopathology are moderated by sex and developmental processes. This causal taxonomy also provides a novel framework for understanding the heterogeneity of each first-order dimension: Different persons exhibiting similar symptoms may be influenced by different combinations of etiologic influences from each of the 3 levels of the etiologic hierarchy. Furthermore, we relate the proposed causal taxonomy to transdimensional psychobiological processes, which also impact the heterogeneity of each psychopathology dimension. This causal taxonomy implies the need for changes in strategies for studying the etiology, psychobiology, prevention, and treatment of psychopathology. (PsycINFO Database Record
Project description:IntroductionSubstance use often co-occurs with both internalizing and externalizing disorders, highlighting the importance of understanding reciprocal relations among problematic drug use and psychopathology. We examined affective (approach and avoidance) motivations for drug use as potential transdiagnostic constructs that relate to symptoms of common clinical disorders.Methods175 community adults with a lifetime history of drug use reported on their motivations for use, frequency of use, and DSM-5 lifetime psychopathology symptoms. Linear regression was used to examine associations between drug use motivations and psychopathology.ResultsAvoidance motivations for drug use (e.g., using to cope with distress) correlated positively with symptoms of both internalizing and externalizing disorders, borderline personality disorder, and psychiatric comorbidity. In contrast, approach motivations for drug use (e.g., using to get a thrill) correlated only with substance use disorder symptoms. Notably, motivations for drug use continued to show these transdiagnostic associations after accounting for general approach-avoidance motivational tendencies.ConclusionThese findings suggest that affective motivations for drug use provide a useful framework for conceptualizing substance problems that cuts across traditional dimensions of psychopathology.