The Bifactor Model of Psychopathology: Methodological Issues and Clinical Applications

For decades, clinicians have debated whether psychiatric problems should be ‘lumped’ into broad dimensions or ‘split’ into discrete entities. The bifactor model provides a potential solution to this debate by including both a general dimension of psychopathological severity known as the p factor, and specific dimensions reflecting specific problem areas such as internalizing and externalizing. This thesis evaluates the methodological properties and clinical utility of the bifactor model. Chapter 3 is a reliability review of bifactor studies and demonstrates that while self-report measures capture both general and specific domains of psychopathology, the total and subscale scores derived mainly reflect a general p factor. Chapter 4 investigates whether the general and specific psychopathology factors are products of response biases (i.e. tendencies in the way people fill out questionnaires), rather than variation in people’s experiences of psychiatric problems. Less than 4% of the variance in the general and specific psychopathology factors was explained by response biases, demonstrating their substantive validity. Chapter 5 analyzes clinical outcomes assessed over a psychosocial intervention for antisocial youth with a bifactor model and demonstrates more nuanced changes in disorder-specific factors after accounting for changes in the p factor (e.g., antisociality declines but anxiety increases over time). Similarly, Chapter 6 demonstrates the prognostic value of specific personality disorders for predicting depression outcomes assessed over an inpatient intervention only after accounting for the prognostic effect of a general personality disorder factor (e.g., borderline personality disorder predicts slower recovery). These findings demonstrate the substantive nature of the general and specific psychopathology factors, but also the difficulties in reliably measuring specific domains beyond general psychopathology. They also support the bifactor model’s utility in untangling clinically relevant effects that are otherwise masked by the shared variance among psychiatric problems

Methodological and Developmental Studies into the Bifactor Model of Psychopathology

This thesis examines the methodological, developmental, and clinical relevance of the bifactor model of psychopathology. The bifactor model organizes mental health problems into a single dimension of psychopathology, e.g., the p factor, which captures aspects shared across disorders, and specific dimensions, e.g., internalizing and externalizing, which capture aspects shared among subgroups of disorders. Part 1 is a reliability meta-analysis of bifactor studies of psychopathology. It uses model-based reliability indices to evaluate how the variance in factor models is distributed and whether this resembles a bifactor structure. Part 2 is a developmental analysis of the relationship between socioeconomic status and the general and specific psychopathology factors. It examines the mediating role of stressful life events, and moderating role of family obligation, in this relationship. Part 3 is a clinically informed evaluation of quantitative models of psychopathology, covering issues related to methodology, epistemology, and clinical application. Part 1 shows that whilst psychopathology measures tend to be multidimensional (e.g., include both general and specific sources of variance), most of what may be measured in practice reflects the p factor. Part 2 shows negative links between socioeconomic status and the p factor and specific externalizing factor, and that these links are partially explained by stressful life events, particularly for children who prioritize their families’ needs and views. Finally, Part 3 argues for more process-based mental health assessments, idiographic and transactional analyses of symptoms, and a focus on the socio-evolutionary role of communication in assessment and treatment

Episodic Antarctic Shelf Intrusions of Circumpolar Deep Water via Canyons

The structure of the Antarctic Slope Current at the continental shelf is crucial in governing the poleward transport of warm water. Canyons on the continental slope may provide a pathway for warm water to cross the slope current and intrude onto the continental shelf underneath ice shelves, which can increase rates of ice shelf melting, leading to reduced buttressing of ice shelves, accelerating glacial flow and hence increased sea level rise. Observations and modelling studies of the Antarctic Slope Current and cross-shelf warm water intrusions are limited, particularly in the East Antarctica region. To explore this topic, an idealised configuration of the Antarctic Slope Current is developed, using an eddy-resolving isopycnal model that emulates the dynamics and topography of the East Antarctic sector. Warm water intrusions via canyons are found to occur in discrete episodes, with large onshore flow induced by eddies. The episodic nature of cross-shelf warm water transport is demonstrated, with canyon width playing a key role in modulating cross-shelf exchanges; warm water transport through narrower canyons is more irregular than transport through wider canyons. The episodic cross-shelf transport is driven by a cycle of rising and falling rates of eddy generation in the Antarctic Slope Current, a variability intrinsic to the slope current that can be explained without any temporal variability in external forcings. Improved understanding of the intrinsic variability of warm water intrusions can help guide future observational and modelling studies in the analysis of eddy impacts on Antarctic shelf circulation

Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis.

Chronological age is a powerful epidemiologic risk factor for osteoarthritis (OA), a multifactorial disease that is characterized by articular cartilage (AC) degradation. It is unclear from a molecular perspective how aging interacts with OA to produce this risk to AC integrity. To address this key question, we used in vivo time-course analysis of OA development and murine interstrain variability in natural susceptibility to OA to examine changes in non-OA-prone CBA mice versus OA-prone STR/Ort mice, which develop disease that bears significant histologic resemblance to human OA. Through global transcriptome profiling, we attempted to discover the molecular signature linked with both OA vulnerability and progression. Affymetrix Mouse Gene 1.0 ST Array profiles were generated from AC samples derived from CBA and STR/Ort mice at 3 different ages, corresponding to the stages prior to, at, and late after the natural onset of OA in the STR/Ort mice. We found that the OA in STR/Ort mice exhibited a molecular phenotype resembling human OA, and we pinpointed a central role of NF-κB signaling and the emergence of an immune-related signature in OA cartilage over time. We discovered that, strikingly, young healthy AC has a highly expressed skeletal muscle gene expression program, which is switched off during maturation, but is intriguingly retained in AC during OA development in STR/Ort mice. This study is the first to show that AC chondrocytes share a high-abundance gene-expression program with skeletal muscle. We show that failure to switch this program off, as well as the restoration of this program, is associated with inappropriate expression of NF-κB signaling pathways, skeletal muscle-related genes, and induction and/or progression of OA. Copyright © 2012 by the American College of Rheumatology

The mediating role of reflective functioning and general psychopathology in the relationship between childhood conduct disorder and adult aggression among offenders

BACKGROUND: The nature of the pathway from conduct disorder (CD) in adolescence to antisocial behavior in adulthood has been debated and the role of certain mediators remains unclear. One perspective is that CD forms part of a general psychopathology dimension, playing a central role in the developmental trajectory. Impairment in reflective functioning (RF), i.e., the capacity to understand one's own and others' mental states, may relate to CD, psychopathology, and aggression. Here, we characterized the structure of psychopathology in adult male-offenders and its role, along with RF, in mediating the relationship between CD in their adolescence and current aggression. METHODS: A secondary analysis of pre-treatment data from 313 probation-supervised offenders was conducted, and measures of CD symptoms, general and specific psychopathology factors, RF, and aggression were evaluated through clinical interviews and questionnaires. RESULTS: Confirmatory factor analyses indicated that a bifactor model best fitted the sample's psychopathology structure, including a general psychopathology factor (p factor) and five specific factors: internalizing, disinhibition, detachment, antagonism, and psychoticism. The structure of RF was fitted to the data using a one-factor model. According to our mediation model, CD significantly predicted the p factor, which was positively linked to RF impairments, resulting in increased aggression. CONCLUSIONS: These findings highlight the critical role of a transdiagnostic approach provided by RF and general psychopathology in explaining the link between CD and aggression. Furthermore, they underscore the potential utility of treatments focusing on RF, such as mentalization-based treatment, in mitigating aggression in offenders with diverse psychopathologies

Evaluating variants classified as pathogenic in ClinVar in the DDD Study.

PURPOSE: Automated variant filtering is an essential part of diagnostic genome-wide sequencing but may generate false negative results. We sought to investigate whether some previously identified pathogenic variants may be being routinely excluded by standard variant filtering pipelines. METHODS: We evaluated variants that were previously classified as pathogenic or likely pathogenic in ClinVar in known developmental disorder genes using exome sequence data from the Deciphering Developmental Disorders (DDD) study. RESULTS: Of these ClinVar pathogenic variants, 3.6% were identified among 13,462 DDD probands, and 1134/1352 (83.9%) had already been independently communicated to clinicians using DDD variant filtering pipelines as plausibly pathogenic. The remaining 218 variants failed consequence, inheritance, or other automated variant filters. Following clinical review of these additional variants, we were able to identify 112 variants in 107 (0.8%) DDD probands as potential diagnoses. CONCLUSION: Lower minor allele frequency (1 star) are good predictors of a previously identified variant being plausibly diagnostic for developmental disorders. However, around half of previously identified pathogenic variants excluded by automated variant filtering did not appear to be disease-causing, underlining the continued need for clinical evaluation of candidate variants as part of the diagnostic process

Global Alliance for the Promotion of Physical Activity : the Hamburg Declaration

Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the â € Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the â € Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The â € Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.Peer reviewe