On the construct validity of interoceptive accuracy based on heartbeat counting: Cardiovascular determinants of absolute and tilt-induced change scores.

Interoceptive accuracy (IAcc) as assessed with the heartbeat counting task (IAccHBCT) may be affected by a range of factors including (1.) the ability to adequately detect cardiac signals, indicated by IAcc in a heartbeat discrimination task (IAccHBDT), (2.) cardiac signal properties, affected by sympathetic and parasympathetic tone, and (3.) non-interoceptive processes, including time estimation accuracy (TEAcc). In the current study we investigated the contribution of these factors to absolute and Δ IAccHBCT scores, induced by passive head-up and head-down tilt in 49 healthy individuals. A set of hierarchical regression models showed IAccHBDT scores as the strongest and, across different orthostatic (tilt) conditions, most stable (positive) predictor of absolute and Δ IAccHBCT scores. Neither indicators of cardiac signal properties (except for HR in head-down-tilt), nor TEAcc predicted absolute or Δ IAccHBCT scores. These findings support the convergent and discriminant validity of absolute and Δ IAccHBCT scores.

Effects of rejection intensity and rejection sensitivity on social approach behavior in women.

OBJECTIVE: Perceived rejection plays an important role for mental health and social integration. This study investigated the impact of rejection intensity and rejection sensitivity on social approach behavior. METHOD: 121 female participants were randomly assigned to one of three conditions differing in the degree of induced rejection (inclusion, medium rejection, severe rejection). Thereafter they were asked to interact with an unknown person during a touch-based cooperative task. RESULTS: Participants high in rejection sensitivity sought significantly less physical contact than participants low in rejection sensitivity. Individuals in the medium rejection condition touched their partners more often than those in the included condition, while no difference between included and severely rejected participants could be observed. CONCLUSIONS: The results suggest that the intensity of rejection matters with regard to coping. While participants in the medium intensity rejection condition aimed to 'repair' their social self by seeking increased contact with others, severely rejected participants did not adapt their behavior compared to included participants. Implications for therapy are discussed.

Glucocorticoid receptor signaling in leukocytes after early life adversity.

Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.

Childhood Trauma Affects Stress-Related Interoceptive Accuracy.

Early life adversity (ELA) may cause permanent disturbances in brain-body signaling. These disturbances are thought to contribute to physical symptoms and emotional dysregulation in adulthood. The current study investigated the effects of childhood trauma on young adults' interoceptive accuracy as an indicator of brain-body communication that may be dysregulated by ELA. Sixty-six participants completed an online questionnaire followed by a laboratory session including the socially evaluated cold pressor stress test during which ECG, salivary cortisol, and interoceptive accuracy were assessed. Childhood trauma was negatively related to interoceptive accuracy (IAc) after the stressor. This stress effect could not be observed for heart rate and cortisol, which were unrelated to IAc. Participants reporting higher baseline unpleasantness exhibited lower IAc after the stressor, while increases in unpleasantness due to the stressor were associated with higher IAc. Unpleasantness at baseline mediated the effect of childhood trauma on IAc after the stressor.

Parental divorce is associated with an increased risk to develop mental disorders in women.

BACKGROUND: Parental divorce has been associated with reduced well-being in young adults. It is, however, unclear whether this finding is clinically relevant as studies using structured clinical interviews are missing. This study, therefore, investigated if young adults with divorced parents are at risk to develop mental disorders. Furthermore, differences in parental care, social connectedness, chronic stress and traumatic experiences between children of divorced and non-divorced parents were investigated. METHODS: 121 women (mean age: 23 years) were interviewed using the Structured Clinical Interview for DSM-IV Axis I (i.e., major mental disorders) and II (i.e., personality disorders) Disorders and asked to complete questionnaires assessing parental care, social connectedness (loneliness, attachment anxiety and avoidance), chronic stress, childhood trauma and depression. RESULTS: Young adults of divorced parents had a higher risk for Axis I but not Axis II disorders as compared to young adults of non-divorced parents. Participants from divorced families as compared to non-divorced families reported more depression, loneliness, childhood trauma, attachment avoidance, attachment anxiety, chronic stress and less paterntal care. LIMITATIONS: Due to the cross-sectional design of this study, conclusions about causality remain speculative. CONCLUSION: The increased vulnerability of children of divorced parents to develop mental disorders, and to experience more chronic stress, loneliness, attachment avoidance, attachment anxiety, and traumatic experiences during childhood is alarming and highlights the importance of prevention programs and psycho-education during the process of parental divorce. Parental support with regard to adequate caregiving is needed to help parents to better support their children during and after their divorce.

Blunted endocrine response to a combined physical-cognitive stressor in adults with early life adversity.

The negative health effects of early life adversity (ELA) continue long into adulthood. Changes in the physiological response to psychosocial stressors have been proposed to mediate this effect. However, many previous studies have come to contradicting conclusions as to whether ELA induces a long-term increase or decrease in stress reactivity. Therefore, we tested the association of ELA exposure and adult stress reactivity in a sample of early life adoptees and controls. Two previously validated stressful elements (bilateral feet CPT and the Paced Auditory Serial Addition Task (PASAT)) were combined in an extended Cold Pressor Test (CPT). This test was performed on 22 participants who had experienced severe ELA (separation from biological parents, institutionalization, and adoption in early childhood), and in 22 age-matched control participants. A prior history of ELA was associated with blunted reactivity of the hypothalamic-pituitary-adrenal (HPA) axis (Cohen´s d = 0.680). Cardiovascular reactivity remained unchanged, and affective reactivity (self-report ratings) were increased in participants exposed to ELA compared to the control group (range Cohen´s d: 0.642-0.879). Our results suggest that the activity of the HPA axis reactivity was inhibited in ELA participants. Importantly, cardiovascular stress responsiveness was not affected by ELA. This separation of the HPA axis and cardiovascular stress responses may best be explained by ELA selectively enhancing central feedback-sensitivity to glucocorticoids, but preserving cardiovascular/ autonomic stress reactivity.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection.

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

Proinflammatory T Cell Status Associated with Early Life Adversity.

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69+CD8+ T cells (p = 0.022), increased numbers of HLA-DR+ CD4 and HLA-DR+ CD8 T cells (p < 0.001), as well as increased numbers of CD25+CD8+ T cells (p = 0.036). ELA also showed a trend toward higher numbers of CCR4+CXCR3-CCR6+ CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.

Resilience and rejection sensitivity mediate long-term outcomes of parental divorce.

Increasing divorce rates leave more and more children to deal with the separation of their parents. Recent research suggests that children of divorced parents more often experience psychological and physical symptoms than children of non-divorced parents. The processes that mediate the relationship between parental divorce and ill-health, however, are still elusive. This study investigated the mediating role of psychological factors such as resilience and rejection sensitivity on the long-term consequences of parental divorce in young adults. One hundred and ninety-nine participants (mean age 22.3 years) completed an online survey, including measures of mental health, childhood trauma, resilience, and rejection sensitivity. Participants with divorced parents (33 %) reported increased levels of psychological symptoms, childhood trauma, rejection sensitivity, and lower levels of resilience. The association between parental divorce and mental health was fully mediated by resilience, rejection sensitivity, and childhood trauma. The mediation model explained up to 44 % of the total variance in mental health symptoms. Resilience and rejection sensitivity are crucial factors for successful coping with the experience of parental separation. Prevention programs that help to boost children's resilience might help to reduce the long-term effects of parental divorce on their attachment style (e.g., rejection sensitivity), thereby improving their mental health on the long run. Furthermore, the results call for parental awareness and counseling to target and reduce the observed increased level of childhood trauma. Limitations concern the cross-sectional and retrospective design of the study.