DunedinPACE, a DNA methylation biomarker of the pace of aging

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods: We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

Psychosocial factors that distinguish between men and women who have suicidal thoughts and attempt suicide: findings from a national probability sample of adults

Background Previous research has highlighted the importance of understanding which psychosocial factors distinguish between those with suicide thoughts compared to those who attempt suicide. This study aims to investigate these distinguishing factors further within an ideation-to-action framework and to explore sex differences in suicide risk. Methods Participants (n = 7546, aged 16+) were from the cross-sectional Adult Psychiatric Morbidity Survey (APMS; 2014) of England. Face-to-face and self-completion questionnaires assessed lifetime suicidal ideation, lifetime suicide attempts, demographic characteristics, life experiences, social support, health and mental illness. Multinomial logistic regression examined factors differentiating between those with suicidal ideation only and suicide attempt histories (with or without suicidal ideation) in men and women. Results Overall men were less likely to report suicidal thoughts and attempts, compared to females. More factors differentiated between suicidal thoughts and attempts in women compared to in men; these included hospital admission for mental illness, below degree level qualifications, being single and childhood adversity. In men, factors which significantly differentiated between suicidal thoughts and attempts included self-report of professional diagnosis of mental illness and childhood adversity. Higher levels of social support were associated with being in the suicidal thoughts group v. in the attempts group in men. Conclusion This study identified some key differences between men and women in factors associated with suicide attempts compared to suicidal thoughts. The findings support the use of the ideation-to-action framework to investigate sex differences in suicidal behaviour. Future research should examine the extent to which these factors are associated with suicide risk over time.

Does childhood trauma predict schizotypal traits? A path modelling approach in a cohort of help-seeking subjects

Schizotypy constitutes a susceptibility to beneficial and deleterious schizotypal traits, ranging from coping mechanisms to schizotypal personality disorder on a psychosis continuum. Growing evidence indicates a relationship between childhood adversity and trauma and schizotypy. However, the exact influence of childhood adversity and trauma on schizotypy and its relation to sex is not sufficiently understood. Therefore, we investigated sex-adjusted connections between childhood adversity and trauma subdomains (emotional/physical/sexual abuse, emotional/physical neglect) and positive (magical ideation, perceptual aberration) as well as negative schizotypy (physical/social anhedonia). In total, 240 outpatients of the Early Detection and Intervention Centre of the University Hospital Cologne were assessed with the Trauma and Distress Scale for childhood adversity and trauma and the Wisconsin Schizotypy Scales for schizotypy. Path analyses were performed to investigate sex-adjusted correlations. The well-fitting path model of the total sample linked emotional abuse to magical ideation (p = 0.03; SE = 0.20) and emotional neglect to social anhedonia (p = 0.01; SE = 0.26). In females, physical abuse predicted magical ideation (p = 0.01; SE = 0.33), while emotional neglect forecasted physical anhedonia (p = 0.03; SE = 0.34) and social anhedonia (p = 0.03; SE = 0.32). In males, sexual abuse predicted perceptive aberration (p = 0.04; SE = 0.19) and emotional abuse forecasted magical ideation (p = 0.03; SE = 0.27). Overall, the significance of sex-specific interrelations between trauma and schizotypy were highlighted. Magical ideation and perceptive aberration occurred prominently in the absence of negative and disorganized schizotypy, thus positive schizotypy could be discussed as a beneficial expression of coping with emotional, physical and sexual abuse. Furthermore, emotional neglect should be addressed particularly to prevent deleterious negative schizotypy in females.Trial registration number (20-1243), date of registration (May 19th 2020), retrospectively registered.