Longitudinal Changes in Epigenetic Age Acceleration Across Childhood and Adolescence.

Importance: Individuals exposed to discrimination may exhibit greater epigenetic age acceleration (ie, cellular indicators of premature aging) over time, but few studies have examined longitudinal changes in epigenetic age acceleration, the heterogeneity in these changes for diverse groups of youths, and contextual explanations (ie, discrimination) for differences by ethnicity or race. Objective: To provide a descriptive illustration of changes in epigenetic age acceleration across childhood and adolescence among an ethnically and racially diverse sample of youths. Design, Setting, and Participants: This cohort study leveraged longitudinal data on a large sample of youths from low-income households in 20 large urban US cities who provided repeated assessments of saliva tissue samples at ages 9 and 15 years for DNA methylation analysis. Of 4898 youths from the Future of Families and Child Well-Being study, an ongoing study that oversampled children born to unmarried parents from 1998 to 2000, 2039 were included in the present analysis, as these youths had salivary DNA methylation data assayed and publicly available. Analyses were conducted from March 2023 to June 2024. Exposures: Racialized intrusive encounters with police (eg, stop and frisk and racial slurs). Main Outcomes and Measures: Analyses were conducted to examine longitudinal changes in salivary epigenetic age acceleration over time, whether such changes varied across ethnically and racially diverse groups of youths, and whether police intrusion was associated with variation across ethnic and racial groups. Results: Among 2039 youths (mean [SD] age at baseline, 9.27 [0.38] years; 1023 [50%] male and 1016 [50%] female; 917 [45%] Black, 430 [21%] Hispanic or Latino, 351 [17%] White, and 341 [17%] other, including multiple races and self-identified other) with salivary epigenetic clocks at 9 and 15 years of age, longitudinal results showed that White youths exhibited less accelerated epigenetic aging over time than did Black and Hispanic or Latino youths and those reporting other or multiple races or ethnicities from ages 9 to 15 years, particularly in the Hannum (B, 1.54; 95% CI, 0.36-2.18), GrimAge (B, 1.31; 95% CI, 0.68-1.97), and DunedinPACE epigenetic clocks (B, 0.27; 95% CI, 0.11-0.44). Across these clocks and the PhenoAge clock, police intrusion was associated with Black youths' more accelerated epigenetic aging (Hannum: B, 0.11; 95% CI, 0.03-0.23; GrimAge: B, 0.09; 95% CI, 0.03-0.18; PhenoAge: B, 0.08; 95% CI, 0.02-0.18; DunedinPACE: B, 0.01; 95% CI, 0.01-0.03). Conclusions and Relevance: The transition from childhood to adolescence may represent a sensitive developmental period when racism can have long-term deleterious impacts on healthy human development across the life span. Future research should build on the present study and interrogate which social regularities and policies may be perpetuating discrimination against ethnically and racially minoritized adolescents.

Where do neurodevelopmental conditions fit in transdiagnostic psychiatric frameworks? Incorporating a new neurodevelopmental spectrum.

Features of autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disorders, intellectual disabilities, and communication and motor disorders usually emerge early in life and are associated with atypical neurodevelopment. These "neurodevelopmental conditions" are grouped together in the DSM-5 and ICD-11 to reflect their shared characteristics. Yet, reliance on categorical diagnoses poses significant challenges in both research and clinical settings (e.g., high co-occurrence, arbitrary diagnostic boundaries, high within-disorder heterogeneity). Taking a transdiagnostic dimensional approach provides a useful alternative for addressing these limitations, accounting for shared underpinnings across neurodevelopmental conditions, and characterizing their common co-occurrence and developmental continuity with other psychiatric conditions. Neurodevelopmental features have not been adequately considered in transdiagnostic psychiatric frameworks, although this would have fundamental implications for research and clinical practices. Growing evidence from studies on the structure of neurodevelopmental and other psychiatric conditions indicates that features of neurodevelopmental conditions cluster together, delineating a "neurodevelopmental spectrum" ranging from normative to impairing profiles. Studies on shared genetic underpinnings, overlapping cognitive and neural profiles, and similar developmental course and efficacy of support/treatment strategies indicate the validity of this neurodevelopmental spectrum. Further, characterizing this spectrum alongside other psychiatric dimensions has clinical utility, as it provides a fuller view of an individual's needs and strengths, and greater prognostic utility than diagnostic categories. Based on this compelling body of evidence, we argue that incorporating a new neurodevelopmental spectrum into transdiagnostic frameworks has considerable potential for transforming our understanding, classification, assessment, and clinical practices around neurodevelopmental and other psychiatric conditions.

Conceptualizing adult ADHD with the DSM alternative model of personality disorder.

Personality traits and personality disorders are related to ADHD and indicate dysfunction in clinical populations. The goals of this study were to examine how the DSM-5 Alternative Model of Personality Disorder (AMPD) a) indicates the presence of ADHD and b) communicates information about dysfunction over and above ADHD diagnosis. A sample of 330 adult psychiatric patients with and without ADHD (60% female; mean age 33 years) were assessed for ADHD symptoms, personality impairment, maladaptive personality traits, and functional life impairment domains. The maladaptive personality domain Disinhibition and particularly the lower order facet of Distractibility distinguished between individuals with psychiatric difficulties with and without ADHD. Distractibility is strongly related to the ADHD symptom dimension Inattentiveness, and Antagonism to Hyperactivity/impulsivity. General personality impairment augmented ADHD diagnosis in predicting life impairments. The AMPD has utility in ADHD assessments for diagnosis and prognosis.

Why does perceived parenting in adolescence predict maladaptive personality in adulthood? Evidence for substantial genetic mediation.

Why is parenting in adolescence predictive of maladaptive personality in adulthood? This study sets out to investigate environmental and genetic factors underlying the association between parenting and maladaptive personality longitudinally in a large sample of twins. The present study addressed this question via a longitudinal study focused on two cohorts of twins assessed on aspects of perceived parenting (parent- and adolescent-reported) at age 14 years (n =1,094 pairs). Participants were followed to adulthood, and maladaptive personality traits were self-reported using the Personality Inventory for DSM-5 (PID-5) at age 24 or 34 years. We then modeled these data using a bivariate biometric model, decomposing parenting-maladaptive personality associations into additive genetic, shared environmental, and nonshared environmental factors. Numerous domains of adolescent-reported parenting predicted adult maladaptive personality. Further, we found evidence for substantial additive genetic (r a ranging from 0.22 to 0.55) and (to a lesser extent) nonshared environmental factors (r e ranging from 0.10 to 0.15) that accounted for the association between perceived parenting reported in adolescence and adult personality. Perceived parenting in adolescence and maladaptive personality in adulthood may be related due to some of the same genetic factors contributing to both phenotypes at different developmental periods.

Mapping Emotion Regulation Patterns Within the Alternative Model of Personality Disorders Personality Traits.

Personality pathology is associated with emotional problems that are potentially attributable to problematic emotion regulation strategy patterns. We evaluated the emotion regulation strategies associated with the pathological personality traits in the Alternative Model of Personality Disorders (AMPD). A total of 504 participants completed measures of AMPD traits and strategy usage, which were analyzed using hierarchical regressions and latent profile analysis (LPA). Regression results demonstrated that each trait was associated with a unique strategy pattern: negative affect with emotional overengagement, detachment with socialemotional avoidance, antagonism with emotional externalization/avoidance, disinhibition with emotional avoidance and overengagement, and psychoticism with strategies linked to psychotic/dissociative experiences. The LPA identified three profiles with heightened AMPD traits: an internalizing/distressed profile, an externalizing/distressed profile, and a schizoid-schizotypal profile; each had a unique strategy pattern that varied depending on trait composition. This research highlights the relevance of emotion regulation strategy patterns in the assessment, conceptualization, and treatment of personality pathology.

Reconceptualizing mental health in cancer survivorship.

Mental health for cancer survivors in both research and clinical applications has strongly adopted a traditional nosological approach, involving the classification of psychopathology into discrete disorders. However, this approach has recently faced considerable criticism due to issues such as high comorbidity and within-disorder symptom heterogeneity across populations. Moreover, there are additional specific issues impacting the validity of traditional approaches in cancer survivorship populations, including the physiological effects of cancer and its treatments. In response, we provide the case for the hierarchical dimensional approach within psycho-oncology, in particular the Hierarchical Taxonomy of Psychopathology (HiTOP). We discuss not only the potential utility of HiTOP to research and clinical applications within psycho-oncology, but also its limitations, and what is required to apply this approach within cancer survivorship.

Associations between epigenetic age acceleration and longitudinal measures of psychosocioeconomic stress and status.

Relationships between epigenetic aging markers and psychosocial variables such as socioeconomic status and stress have been well-documented, but are often examined cross-sectionally or retrospectively, and have tended to focus on objective markers of SES or major life events. Here, we examined associations between psychosocial variables, including measures of socioeconomic status and social stress, and epigenetic aging markers in adulthood, using longitudinal data spanning three decades from the Midlife in the United States (MIDUS) study. The largest effects were observed for epigenetic markers of change in health, such as DunedinPACE and GrimAge, and for associations involving education, income, net assets, general social stress, inequality-related stress, and financial stress. Analyses of polygenic indices suggests that at least in the case of education, the link to epigenetic aging cannot be accounted for by common genetic variants.

Maladaptive personality traits and older adult relationship satisfaction: A co-twin control approach to understanding associations.

OBJECTIVE: Maladaptive personality traits have been implicated in romantic relationship dissatisfaction, but the etiology of those links and the degree to which they extend to other types of relationships are unclear. The purpose of this study was to examine associations between maladaptive personality traits and satisfaction in various relationships using a co-twin control design to identify potential environmental contributions. METHOD: The sample consisted of 1340 older adult twin participants from the Minnesota Twin Registry (Mage = 70.3) that completed the Personality Inventory for DSM-5 Faceted Brief Form and Network of Relationships Inventory (Revised for Older Adults). RESULTS: Several maladaptive personality traits were phenotypically associated with relationship dissatisfaction, with detachment and negative affect having the largest effects. Further, within twin pair differences in detachment and negative affect were associated with greater relationship dissatisfaction, suggesting that observed associations were mediated partly by the unique environment, not solely the result of genetic and familial confounding. Both phenotypic and co-twin associations were strongest overall in the romantic partner relationship. CONCLUSION: These findings support the notion that maladaptive personality traits are implicated in interpersonal dysfunction across multiple domains.

Predicting nonsuicidal self-injury and suicidal risk: A comparison between the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Section II personality disorder and alternative model of personality disorders dimensions.

The clinical relevance of nonsuicidal self-injury (NSSI) has received growing recognition, and NSSI represents a relevant risk factor for suicide. The present study aimed at running a head-to-head comparison between interview scores of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Section II personality disorders (PDs) criteria, and DSM-5 Alternative Model of Personality Disorder (AMPD) Criterion A and Criterion B measures in providing significant and relevant information for understanding NSSI and suicidal ideation and behavior among psychotherapy participants. To this aim, a clinical sample of 103 adult participants was administered the Clinician-Administered Nonsuicidal Self-Injury Disorder Index (CANDI), the Columbia Suicide Severity Rating Scale (C-SSRS), as well as the Structured Clinical Interview for DSM-5 Personality Disorders, the Structured Clinical Interview for the DSM-5 Alternative Model for Personality Disorders Module I, and a self-report measure of dysfunctional personality traits (i.e., the Personality Inventory for DSM-5 [PID-5]). Logistic ordinal regression dominance analysis results showed that, when compared to the 10 DSM-5 Section II PD symptom counts, the DSM-5 Section III PD measure scores provided the same amount of information in the CANDI Global Severity Index scores (Nagelkerke pseudo-R² value = .41), and a markedly larger information quantity in the case of the C-SSRS Suicidal Ideation (+35.1%), and Suicidal Behavior Index (+35.9%) levels. As a whole, our data suggested the clinical usefulness of the DSM-5 AMPD in understanding NSSI and suicidal ideation and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Loneliness, epigenetic age acceleration, and chronic health conditions.

Having associations with a range of adverse physical health outcomes including mortality, loneliness is increasingly recognized as a pressing public health concern, but the mechanisms studied to date do not yet explain all loneliness-related health risk. We sought to evaluate whether epigenetic influences on DNA methylation could help explain the relationship between loneliness and health. To do so, we first estimated associations between loneliness and epigenetic age acceleration (EAA) in a subsample of participants in the study of midlife in the United States (n = 1,310), before testing whether EAA mediated and/or moderated the association between loneliness and the onset of chronic health conditions in older adulthood (n = 445 completing longitudinal follow-ups). Greater loneliness was weakly associated with greater EAA in the Horvath, DunedinPACE, and GrimAge measures after accounting for demographic (0.08 ≤ ß ≤ 0.11) and behavioral (0.06 ≤ ß ≤ 0.08) covariates. Loneliness also predicted increases in chronic condition counts and these effects were more pronounced for individuals with higher DunedinPACE EAA values (interaction term ß = 0.09, p = .009), suggesting possible synergistic impacts. EAA measures appear to be promising in helping to understand individual variations in the health impacts of loneliness, but the specific mechanisms involved require further research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A novel approach to model cumulative stress: Area under the s-factor curve.

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.

Is it time to discard the Diagnostic and Statistical Manual of Mental Disorders (DSM) in psycho-oncology?

The conceptual basis of psychopathology within cancer survivorship is critical, as the chosen conceptualisation informs assessment and explanatory models, as well as interventions and supportive care approaches. The validity of a chosen conceptualisation of psychopathology is therefore paramount for ensuring cancer survivors receive high-quality and efficacious care and support that can be iteratively improved via coordinated research efforts. In this paper, we discuss the traditional diagnostic approach to conceptualising psychopathology within cancer care, including the diagnostic system the 'Diagnostic and Statistical Manual of Mental Disorders' (DSM) [1], and the significant issues it presents within cancer survivorship. We detail and discuss how an alternate conceptualisation of psychopathology may enhance both research and practice within psycho-oncology. We ultimately pose, and provide our perspective, on the question "Is it Time to Discard the DSM in Psycho-Oncology?"

Connecting loneliness with pathological personality traits: Evidence for genetic and environmental mediation from a study of older twins.

Loneliness has broad public health importance, especially in older adulthood, and there is some evidence suggesting it is associated with several personality disorders (PDs). The etiology of these PD-loneliness associations, however, has rarely been studied, especially in the context of the maladaptive traits of the DSM-5 alternative model of personality disorder (AMPD). To address these limitations, we estimated phenotypic, genetic, and unique environmental associations between loneliness and maladaptive personality traits in a sample of older adults from the Minnesota Twin Registry (n = 1,356, Mage = 70.4). Loneliness was moderately to strongly associated with each of the AMPD domains of negative affect, detachment, antagonism, disinhibition, and psychoticism (r = .22-.58), with evidence of both genetic (rg = .45-.75) and unique environmental (re = .10-.48) influences explaining the associations to varying degrees. We argue that loneliness may be an underappreciated concomitant of personality pathology, with PD traits perhaps underlying its development. Indeed, these findings suggest that loneliness may be a manifestation of the genetic and environmental forces that also lead to pathological personality variation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Linking genetic foundations of sleep disturbances to personality traits: a study of mid-life twins.

Risk of sleep disturbances depends on individuals' personality, and a large body of evidence indicates that individuals prone to neuroticism, impulsivity, and (low) extraversion are more likely to experience them. Origins of these associations are unclear, but common genetic background may play an important role. Participants included 405 twin pairs (mean age of 54 years; 59% female) from the National Survey of Midlife Development in the United States (MIDUS) who reported on their personality traits (broad and specific), as well as sleep disturbances (problems with falling asleep, staying asleep, waking early, and feeling unrested). Uni- and bivariate biometric decompositions evaluated contributions of genetic and environmental factors to associations between personality and poor sleep, as well as unique contributions from individual traits. Neuroticism, extraversion, conscientiousness, and aggressiveness were the strongest phenotypic predictors of poor sleep. Genetic sources of covariance were about twice as large as non-shared environmental sources, and only shared genetic background accounted for links between aggressiveness and poor sleep. Neuroticism and extraversion accounted for most of the genetic overlap between personality and sleep disturbances. The findings shed light on developmental antecedents of ties between personality and poor sleep, suggesting a larger role of common genetic background than idiosyncratic life experiences. The results also suggest that emotion-related traits play the most important role for poor sleep, compared to other personality traits, and may partially account for genetic associations with other traits.

Principles and procedures for revising the hierarchical taxonomy of psychopathology.

Quantitative, empirical approaches to establishing the structure of psychopathology hold promise to improve on traditional psychiatric classification systems. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a framework that summarizes the substantial and growing body of quantitative evidence on the structure of psychopathology. To achieve its aims, HiTOP must incorporate emerging research in a systematic, ongoing fashion. In this article, we describe the historical context and grounding of the principles and procedures for revising the HiTOP framework. Informed by strengths and shortcomings of previous classification systems, the proposed revisions protocol is a formalized system focused around three pillars: (a) prioritizing systematic evaluation of quantitative evidence by a set of transparent criteria and processes, (b) balancing stability with flexibility, and (c) promoting inclusion over gatekeeping in all aspects of the process. We detail how the revisions protocol will be applied in practice, including the scientific and administrative aspects of the process. Additionally, we describe areas of the HiTOP structure that will be a focus of early revisions and outline challenges for the revisions protocol moving forward. The proposed revisions protocol is designed to ensure that the HiTOP framework reflects the current state of scientific knowledge on the structure of psychopathology and fulfils its potential to advance clinical research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.

Assessing the measurement invariance of the Personality Inventory for DSM-5 across Black and White americans.

The Personality Inventory for DSM-5 (PID-5) is the primary tool for assessing maladaptive personality traits within the DSM-5 alternative model for personality disorders. Evidence has begun to accumulate on the replicability and measurement invariance of its five-domain factor structure across countries, clinical and community populations, and sex, but its equivalency across racial groups within a given country is largely unstudied. Attempting to replicate the evidence of noninvariance demonstrated by Bagby et al. (2022), we examined the factor structure of the PID-5 across White Americans (n = 612) and Black Americans (n = 613) within the United States. The five-domain structure emerged across both samples with reasonably congruent factor loadings. Therefore, we tested for measurement invariance using the 13-step framework advocated by Marsh et al. (2009) for personality data. We found support for the PID-5's comparability across racial groups, offering some preliminary backing for its use with Black Americans, though additional evidence is needed to clarify the conflicting results and further validate the instrument. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A cybernetic perspective on the nature of psychopathology: Transcending conceptions of mental illness as statistical deviance and brain disease.

Explicitly or implicitly, psychopathology is often defined in terms of statistical deviance, requiring that an affected individual be sufficiently distant from the norm in some dimension of psychological or neural function. In recent decades, the dominant paradigm in psychiatric research has focused primarily on deviance in neural function, treating psychopathology as disease of the brain. We argue that these conceptualizations are misguided. We recently proposed a novel theory of psychopathology, based in cybernetics and drawing additionally from neuroscience, psychometrics, and personality theory (DeYoung & Krueger, 2018a). In this theory, deviations from the norm in psychological and neural functioning serve as important risk factors for psychopathology but are not in themselves necessary or sufficient to identify psychopathology, which requires the presence of cybernetic dysfunction. Psychopathology is defined as persistent failure to move toward one's goals, due to failure to generate effective new goals, interpretations, or strategies when existing ones prove unsuccessful. We argue that adopting a cybernetic theory to replace conceptualizations of psychopathology as statistical deviance or brain disease would facilitate improvements in measurement, diagnosis, prevention, and treatment of psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pathological personality in relation to multiple domains of quality of life and impairment: Evidence for the specific relevance of the maladaptive poles of major trait domains.

The current study examined whether personality domains have nonmonotonic relationships with functional outcomes, specifically in relation to quality of life and impairment. Four samples were utilized, which were drawn from the United States and Germany. Personality trait domains were measured via the IPIP-NEO and PID-5; quality of life (QoL) was measured with the WHOQOL-BREF, and impairment was measured using the WHODAS-2.0. The PID-5 was analyzed in all four samples. Two-line testing, which fits two spline regression lines separated at a break point, was conducted to evaluate potential nonmonotonicity of the relationship between personality traits and quality of life. Overall, results demonstrated little support for nonmonotonic relationships in the PID-5 and IPIP-NEO dimensions. Rather, our results indicate that there is one clear pathological pole of major domains of personality that is associated with lower quality of life and increased impairment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Discrimination Exposure and Polygenic Risk for Obesity in Adulthood: Testing Gene-Environment Correlations and Interactions.

INTRODUCTION: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene × environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation). METHODS: This was an observational study of 4,102 white/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination Scale items. Polygenic risk scores (PRSs) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. RESULTS: We found that greater PRS-BMI was significantly associated with more reports of discrimination (ß = 0.04 ± 0.02; p = 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively. CONCLUSION: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population level.