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The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures than traditional categorical diagnoses given its enhanced reliability. However, one complication is that observed biological correlates of clinical symptoms can reflect various factors, ranging from dispositional risk to consequences of psychopathology. In this paper, we argue that the HiTOP model provides an optimized framework for conducting research on the biological correlates of psychopathology from an ontogenetic perspective that distinguishes among indicators of liability, current symptoms, and consequences of illness. Through this approach, neurobiological research can contribute more effectively to identifying individuals at high dispositional risk, indexing treatment-related gains, and monitoring the consequences of mental illness, consistent with the aims of the HiTOP framework.
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Theoretical and methodological research on threat conditioning provides important neuroscience-informed approaches to studying fear and anxiety. The threat conditioning framework is at the vanguard of physiological and neurobiological research into core mechanistic symptoms of anxiety-related psychopathology, providing detailed models of neural circuitry underlying variability in clinically relevant behaviors (e.g., decreased extinction, heightened generalization) and heterogeneity in clinical anxiety presentations. Despite the strengths of this approach in explaining symptom and syndromal heterogeneity, the vast majority of psychopathology-oriented threat conditioning work has been conducted using Diagnostic and Statistical Manualof Mental Disorders (DSM) diagnostic categories, which fail to capture the symptom-level resolution that is afforded by threat conditioning indices. Furthermore, relations between fine-grained neurobehavioral measures of threat conditioning and anxiety traits and symptoms are substantially attenuated by within-category heterogeneity, arbitrary boundaries, and inherent comorbidity in the DSM approach. Conversely, the Hierarchical Taxonomy of Psychopathology (HiTOP) is a promising approach for modeling anxiety symptoms relevant to threat conditioning work and for relating threat conditioning to broader anxiety-related constructs. To date, HiTOP has had a minimal impact on the threat conditioning field. Here, we propose that combining the HiTOP and neurobehavioral threat conditioning approaches is an important next step in studying anxiety-related pathology. We provide a brief review of prominent DSM critiques and how they affect threat conditioning studies and review relevant research and suggest solutions and recommendations that flow from the HiTOP perspective. Our hope is that this effort serves as both an inflection point and practical primer for HiTOP-aligned threat conditioning research that benefits both fields. General Scientific Summary: Threat conditioning is a commonly used model for understanding and developing treatments for anxiety-related disorders and mental health problems. Threat conditioning studies commonly use the Diagnostic and Statistical Manual of Mental Disorders to define anxiety-related disorders, yet this system has notable limitations. Here, we discuss how an alternative system, the Hierarchical Taxonomy of Psychopathology, addresses these limitations and can further neuroscience-informed research on threat conditioning and anxiety. [ABSTRACT FROM AUTHOR]

Given the increasing use of threat conditioning and generalization for clinical‐translational research efforts, establishing test–retest reliability of these paradigms is necessary. Specifically, it is an empirical question whether the same participant evinces a similar generalization gradient of conditioned responses across two sessions with the identical contingencies and stimuli. Here, 46 human volunteers participated in an identical auditory threat acquisition and generalization protocol at two sessions separated by 1‐to‐2 weeks. Skin conductance responses (SCR) and trial‐by‐trial shock risk ratings served as primary measures. We used linear mixed effects modeling to test differential threat responses and generalization gradients, and Generalizability (G) theory coefficients as our primary formal assessment of test–retest reliability of intraindividual stability and change across time. Results showed largely invariant differential conditioning and generalization gradients across time. G coefficients indicated fair reliability for acquisition and generalization SCR. In contrast, risk rating reliabilities were mixed, and reliability was particularly low for acquisition risk ratings. Our findings generally support reliability of the threat conditioning and generalization paradigm for shorter test–retest intervals and highlight their utility for assessments of behavioral interventions in mental health research, but challenges remain and further work is needed. Threat conditioning and generalization tasks are increasingly used for translational efforts to improve behavioral interventions, and thus test–retest reliability for these tasks needs to be established. Our results support the test–retest reliability of threat conditioning and generalization over a relatively short (1‐to‐2 week) interval, but this depends on the measure used (physiological vs. self‐report). Overall, these tasks could be appropriate for repeated testing over the course of a short‐duration intervention study, but more research is needed, particularly in regard to longer‐duration studies. Threat (fear) conditioning and generalization tasks are increasingly used for translational efforts to improve behavioral interventions, and thus test‐retest reliability for these tasks needs to be established. Our results support the test‐retest reliability of threat conditioning and generalization over a relatively short (1‐to‐2 week) interval, but this depends on the measure used (physiological vs. self‐report). Overall, these tasks could be appropriate for repeated testing over the course of a short‐duration intervention study, but more research is needed, particularly in regard to longer‐duration studies. [ABSTRACT FROM AUTHOR]

Dimensional models of obsessive-compulsive (OC) symptoms, as seen in obsessive-compulsive disorder (OCD), are instrumental in explaining the heterogeneity observed in this condition and for informing cutting-edge assessments. Prior structural work in this area finds that OC symptoms cross-load under both Negative Affectivity and Psychoticism traits within the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) Alternative Model of Personality Disorder (AMPD). However, tests of OC symptoms in conjunction with assessments of the full AMPD structure and its 25 lower-level facets representing narrower symptom content are lacking. We applied joint exploratory factor analysis to an AMPD measure (Personality Inventory for DSM-5 ; PID-5) and OC symptom data from two separate samples (total N = 1,506) to locate OC symptoms within AMPD space. OC symptoms cross-loaded on Negative Affectivity, Psychoticism, and on the low end of Disinhibition. We also report exploratory analyses of OC symptom subscales with PID-5 variables. Results are discussed in the context OC symptoms' location in PID-5 space, implications for assessment, and placement of OCD within the Hierarchical Taxonomy of Psychopathology. [ABSTRACT FROM AUTHOR]

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators—P3 and error-related negativity (ERN)—were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex—suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy. General Scientific Summary: The Hierarchical Taxonomy Model of Psychopathology argues that some etiological factors might operate at broader levels of the psychopathological spectrum, conferring general risk for clinical problems. Our results show that error-related negativity (ERN) and P3 responses are indicators of distinct neural processes and that both account for externalizing proneness. [ABSTRACT FROM AUTHOR]