Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10−15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Are psychotic psychopathology and neurocognition orthogonal? a systematic review of their associations

Author(s): Ruggero, Camilo J; Kotov, Roman; Hopwood, Christopher J; First, Michael; Clark, Lee Anna; Skodol, Andrew E; Mullins-Sweatt, Stephanie N; Patrick, Christopher J; Bach, Bo; Cicero, David C; Docherty, Anna; Simms, Leonard J; Bagby, R Michael; Krueger, Robert F; Callahan, Jennifer L; Chmielewski, Michael; Conway, Christopher C; De Clercq, Barbara; Dornbach-Bender, Allison; Eaton, Nicholas R; Forbes, Miriam K; Forbush, Kelsie T; Haltigan, John D; Miller, Joshua D; Morey, Leslie C; Patalay, Praveetha; Regier, Darrel A; Reininghaus, Ulrich; Shackman, Alexander J; Waszczuk, Monika A; Watson, David; Wright, Aidan GC; Zimmermann, Johannes | Abstract: ObjectiveDiagnosis is a cornerstone of clinical practice for mental health care providers, yet traditional diagnostic systems have well-known shortcomings, including inadequate reliability, high comorbidity, and marked within-diagnosis heterogeneity. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a data-driven, hierarchically based alternative to traditional classifications that conceptualizes psychopathology as a set of dimensions organized into increasingly broad, transdiagnostic spectra. Prior work has shown that using a dimensional approach improves reliability and validity, but translating a model like HiTOP into a workable system that is useful for health care providers remains a major challenge.MethodThe present work outlines the HiTOP model and describes the core principles to guide its integration into clinical practice.ResultsPotential advantages and limitations of the HiTOP model for clinical utility are reviewed, including with respect to case conceptualization and treatment planning. A HiTOP approach to practice is illustrated and contrasted with an approach based on traditional nosology. Common barriers to using HiTOP in real-world health care settings and solutions to these barriers are discussed.ConclusionsHiTOP represents a viable alternative to classifying mental illness that can be integrated into practice today, although research is needed to further establish its utility. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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Integrating the Hierarchical Taxonomy of Psychopathology (HiTOP) into clinical practice

Poster #70 PREDICTING DEFICIT/NONDEFICIT CATEGORIZATION FROM THE SCALE FOR THE ASSESSMENT OF NEGATIVE SYMPTOMS (SANS)

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): III. Emotional dysfunction superspectrum

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20730

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum.

Authoritative classification systems for psychopathology such as the DSM and ICD are shifting toward more dimensional approaches in the field of personality disorders (PDs). In this paper, we provide a brief overview of the dimensionally oriented DSM-5 alternative model of PDs (AMPD). Since its publication in 2013, the AMPD has inspired a substantial number of studies, underlining its generative influence on the field. Generally speaking, this literature illustrates both the reliability and validity of the constructs delineated in the AMPD. The literature also illustrates empirical challenges to the conceptual clarity of the AMPD, such as evidence of substantial correlations between indices of personality functioning (criterion A in the AMPD) and maladaptive personality traits (criterion B in the AMPD). Key future directions pertain to linking the AMPD literature with applied efforts to improve the lives of persons who suffer from PDs, and surmounting challenges germane to the evolution of the DSM itself.

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Kelsey A Hobbs

Papers

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum.

An Overview of the DSM-5 Alternative Model of Personality Disorders

Big Five Personality and CTRA gene expression: Lack of association in a midlife sample of US adults (MIDUS-Refresher).