Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects ≥60 years old; these subjects included 78 MZ twin pairs and 108 single-born individuals. No such findings were observed in 81 MZ pairs or 180 single-born subjects who were ≤55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence.

Terror management theory (TMT) posits that cultural worldviews and self-esteem function to buffer humans from mortality-related anxiety. TMT research has shown that important behaviors are influenced by mortality salience (MS) even when they have no obvious connection to death. However, there has been no attempt to investigate TMT processes in anxious responding. The present research examines that question. In Study 1, compared to a control condition, MS increased anxious responding to spider-related stimuli, but only for participants who met criteria for specific phobia. In Study 2, compared to an aversive control condition, MS increased time spent washing hands, but only for those scoring high on a measure of compulsive hand washing (CHW). In Study 3, compared to a different aversive control condition, MS increased avoidance of a social interaction, but only for those scoring high on a measure of social interaction anxiety. The relevance of TMT in anxious responding is discussed.

DNA methylation at multiple CpG sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. Our results highlight the importance of testing the combined effects of multiple CpG loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.

Background Systemic inflammation and pain sensitivity may contribute to the development and maintenance of chronic pain conditions. Purpose We examined the relationship between systemic inflammation as measured by C-reactive protein (CRP), and cold pain sensitivity in 198 female twins from the University of Washington Twin Registry. We also explored the potential role of familial factors in this relationship. Methods Linear regression modeling with generalized estimating equations examined the overall and within-pair associations. Results Higher levels of CRP were associated with higher pain sensitivity ratings at pain threshold (p = 0.02) and tolerance (p = 0.03) after adjusting for age, body mass index, time to reach pain threshold or tolerance, and clinical pain status. The magnitude of the associations remained the same in within-pair analyses controlling for familial factors. Conclusions The link between CRP and pain sensitivity may be due to non-shared environmental factors. CRP and pain sensitivity can be examined as potential biomarkers for chronic pain and other inflammatory conditions.

Background Informal caregiving can be deleterious to mental health, but research results are inconsistent and may reflect an interaction between caregiving and vulnerability to stress. Methods We examined psychological distress among 1,228 female caregiving and non-caregiving twins. By examining monozygotic and dizygotic twin pairs discordant for caregiving, we assessed the extent to which distress is directly related to caregiving or confounded by common genes and environmental exposures. Results Caregiving was associated with distress as measured by mental health functioning, anxiety, perceived stress, and depression. The overall association between caregiving and distress was confounded by common genes and environment for mental health functioning, anxiety, and depression. Common environment also confounded the association of caregiving and perceived stress. Conclusions Vulnerability to distress is a factor in predicting caregivers' psychosocial functioning. Additional research is needed to explicate the mechanisms by which common genes and environment increase the risk of distress among informal caregivers.