Monika A. Waszczuk

The Hierarchical Taxonomy of Psychopathology (HiTOP) : A Dimensional Alternative to Traditional Nosologies

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures.

The time has come for dimensional personality disorder diagnosis

Author(s): Hopwood, Christopher J; Kotov, Roman; Krueger, Robert F; Watson, David; Widiger, Thomas A; Althoff, Robert R; Ansell, Emily B; Bach, Bo; Michael Bagby, R; Blais, Mark A; Bornovalova, Marina A; Chmielewski, Michael; Cicero, David C; Conway, Christopher; De Clercq, Barbara; De Fruyt, Filip; Docherty, Anna R; Eaton, Nicholas R; Edens, John F; Forbes, Miriam K; Forbush, Kelsie T; Hengartner, Michael P; Ivanova, Masha Y; Leising, Daniel; John Livesley, W; Lukowitsky, Mark R; Lynam, Donald R; Markon, Kristian E; Miller, Joshua D; Morey, Leslie C; Mullins-Sweatt, Stephanie N; Hans Ormel, J; Patrick, Christopher J; Pincus, Aaron L; Ruggero, Camilo; Samuel, Douglas B; Sellbom, Martin; Slade, Tim; Tackett, Jennifer L; Thomas, Katherine M; Trull, Timothy J; Vachon, David D; Waldman, Irwin D; Waszczuk, Monika A; Waugh, Mark H; Wright, Aidan GC; Yalch, Mathew M; Zald, David H; Zimmermann, Johannes

Hierarchical structure of emotional disorders: From individual symptoms to the spectrum.

Classification of emotional disorders faces challenges of within-disorder heterogeneity and between-disorder comorbidity. The current study addressed these issues by analyzing all emotional disorder symptoms to identify homogeneous dimensions that characterize this domain. These dimensions were, in turn, used to define coherent syndromes and higher order factors. All of the emotional disorder symptoms specified in diagnostic manuals were assessed by interview in 2 treatment-seeking samples (N = 426 and 305), alongside clinical diagnoses and functioning measures. Exploratory and confirmatory factor analyses were employed to elucidate replicable lower and higher order structures. We found 31 homogenous symptom dimensions that clustered, at different levels of generality, into 8 syndromes (Vegetative Symptoms, Cognitive Depression, Posttraumatic Stress Disorder, Panic, Social Anxiety, Phobia, Obsessive–Compulsive Disorder [OCD], and Mania), 3 subfactors (Distress, Fear, and OCD/Mania), and a single Internalizing spectrum. This structure replicated in both samples. Identified dimensions showed considerable convergence with categorical diagnoses, but provided more information about global functioning than diagnoses. Overall, current results propose a novel comprehensive description of the lower order structure of emotional disorders. The empirical syndromes generally paralleled disorders listed in diagnostic manuals, although several differences were notable. The higher order results also confirmed previously reported Distress, Fear, and Mania subfactors of the Internalizing spectrum using homogeneous dimensional markers. Taken together, results highlight a bottom-up approach to constructing an empirical nosology that does not rely on analysis of diagnostic categories. The resulting hierarchical system can be used clinically and to facilitate research on the pathophysiology of emotional disorders, which, in turn, can inform intervention and prevention.

Progress in achieving quantitative classification of psychopathology

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad “spectrum level” dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the “problem of comorbidity” by explicitly modeling patterns of co‐occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders

Previous epigenome-wide association studies (EWAS) of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) have been inconsistent. This may be due to small sample sizes, and measurement and tissue differences. The current two EWA analyses of 473 World Trade Center responders are the largest to date for both PTSD and MDD. These analyses investigated DNA methylation patterns and biological pathways influenced by differentially methylated genes associated with each disorder. Methylation was profiled on blood samples using Illumina 450 K Beadchip. Two EWA analyses compared current versus never PTSD, and current versus never MDD, adjusting for cell types and demographic confounders. Pathway and gene set enrichment analyses were performed to understand the complex biological systems of PTSD and MDD. No significant epigenome-wide associations were found for PTSD or MDD at an FDR P<0.05. The majority of genes with differential methylation at a suggestive threshold did not overlap between the two disorders. Pathways significant in PTSD included a regulator of synaptic plasticity, oxytocin signaling, cholinergic synapse and inflammatory disease pathways, while only phosphatidylinositol signaling and cell cycle pathways emerged in MDD. The failure of the current EWA analyses to detect significant epigenome-wide associations is in contrast with disparate findings from previous, smaller EWA and candidate gene studies of PTSD and MDD. Enriched gene sets involved in several biological pathways, including stress response, inflammation and physical health, were identified in PTSD, supporting the view that multiple genes play a role in this complex disorder.

What do clinicians treat: Diagnoses or symptoms? The incremental validity of a symptom-based, dimensional characterization of emotional disorders in predicting medication prescription patterns

BACKGROUND Although practice guidelines are based on disorders specified in diagnostic manuals, such as the DSM, practitioners appear to follow symptoms when making treatment decisions. Psychiatric medication is generally prescribed in a transdiagnostic manner, further highlighting how symptoms, not diagnoses, often guide clinical practice. A quantitative approach to nosology promises to provide better guidance as it describes psychopathology dimensionally and its organization reflects patterns of covariation among symptoms. AIM To investigate whether a quantitative classification of emotional disorders can account for naturalistic medication prescription patterns better than traditional diagnoses. METHODS Symptom dimensions and DSM diagnoses of emotional disorders, as well as prescribed medications, were assessed using interviews in a psychiatric outpatient sample (N=318, mean age 42.5years old, 59% female, 81% Caucasian). RESULTS Each diagnosis was associated with prescription of multiple medication classes, and most medications were associated with multiple disorders. This was largely due to heterogeneity of clinical diagnoses, with narrow, homogenous dimensions underpinning diagnoses showing different medication profiles. Symptom dimensions predicted medication prescription better than DSM diagnoses, irrespective of whether this was examined broadly across all conditions, or focused on a specific disorder and medication indicated for it. CONCLUSIONS Psychiatric medication was prescribed in line with symptoms rather than DSM diagnoses. A quantitative approach to nosology may better reflect treatment planning and be a more effective guide to pharmacotherapy than traditional diagnoses. This adds to a diverse body of evidence about superiority of the quantitative system in practical applications and highlights its potential to improve psychiatric care.

Pathway from PTSD to respiratory health: Longitudinal evidence from a psychosocial intervention.

Objective: Respiratory illness and posttraumatic stress disorder (PTSD) are common debilitating conditions that frequently co-occur. Observational studies indicate that PTSD, independently of smoking, is a major risk and maintenance factor for lower respiratory symptoms (LRS). The current study experimentally tested this etiologic pathway by investigating whether LRS can be reduced by treating PTSD symptoms. Method: Ninety daily smokers exposed to the World Trade Center (WTC) disaster (mean age 50 years, 28% female; 68% White) completed 8-session group-based weekly comprehensive trauma management and smoking cessation treatment that focused on skills to alleviate PTSD symptoms. LRS, PTSD symptoms, and smoking were assessed weekly. Data was analyzed using multilevel models of within-person associations between LRS, PTSD symptoms, smoking, and treatment dose across 8 weekly sessions with concurrent and lagged outcomes. Results: LRS improved significantly with treatment (reduction of .50 standard deviations). Reduction in PTSD symptoms uniquely predicted improvement in LRS at consecutive sessions 1 week apart and fully accounted for the treatment effect on LRS. The effect of PTSD symptoms was stronger than that of smoking, and the only effect to remain significant when both entered the model. Notably, reduction in LRS did not predict future improvement in PTSD symptoms. Conclusions: The results are in line with the etiologic pathway suggesting that PTSD symptoms are a risk and maintenance factor for chronic LRS and that treatment of PTSD can help to alleviate LRS in trauma-exposed populations. PTSD is emerging as a novel and important treatment target for chronic respiratory problems.

Enhancing Psychosis-Spectrum Nosology Through an International Data Sharing Initiative

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

Mapping emotional disorders at the finest level: Convergent validity and joint structure based on alternative measures

BACKGROUND Traditional categorization of emotional disorders suffers from within-disorder heterogeneity and excessive comorbidity. Quantitative nosology instead proposes grouping homogenous components of these disorders within a higher order internalizing dimension. However, the precise number, composition, and hierarchical structure of these components remains unclear and varies based on assessment tools. METHODS The present study jointly examined two assessment systems with the broadest coverage of homogeneous emotional disorder components-the revised Interview for Mood and Anxiety Symptoms (IMAS-R) and the self-report-based expanded version of the Inventory of Depression and Anxiety Symptoms (IDAS-II)-to map their convergent and discriminant validity and joint structure in outpatient (N=426) and treated student (N=306) samples. RESULTS Results identified 33 non-redundant components of emotional disorders. Most demonstrated strong convergent and discriminant validity between these two instruments. However, the IMAS-R provided more detailed and differentiated characterization of the content subsumed within three IDAS-II scales, and seven of the 33 components were unique to one measure or the other. Joint analysis of scales from both measures supported a four factor (i.e., distress, fear, OCD, mania) mid-level structure of emotional disorders. CONCLUSIONS Using multiple measures, methods, and samples, the present study provided evidence for the validity of core lower order components of the internalizing dimension and suggested they cluster into as many as four distinct factors reflecting distress, fear, OCD, and mania.

Proton pump inhibitors and the risk of severe cognitive impairment: The role of posttraumatic stress disorder

Proton pump inhibitors (PPIs), a common treatment for gastroesophageal reflux disease (GERD), were recently associated with increased risk of dementia. However, severe or chronic stress including, for example, posttraumatic stress disorder (PTSD) was not accounted for. This study examined whether PPI use was associated with severe cognitive impairment (SCI) and whether PTSD explained this association in a cohort of World Trade Center (WTC) responders.