Stability and inter-family associations of hair endocannabinoid and N-acylethanolamines across the perinatal period in mothers, fathers, and children.

Analysis of endocannabinoids (ECs) and N-acylethanolamines (NAEs) in hair is assumed to retrospectively assess long-term EC/NAE concentrations. To inform their use, this study investigated stability of EC/NAE hair concentrations in mothers, fathers, and their children across the perinatal period as well as associations between family members. In a prospective cohort study, EC (AEA, 1-AG/2-AG) and NAE (SEA, PEA, OEA) levels were quantified in hair samples taken four times in mothers (n = 336) and their partners (n = 225) from pregnancy to two years postpartum and in offspring (n = 319) from shortly after birth to two years postpartum. Across the perinatal period, maternal and paternal hair ECs/NAEs showed poor multiple-test consistency (16-36%) and variable relative stability, as well as inconsistent absolute stability for mothers. Regarding children, hair ECs/NAEs evidenced poor multiple-test consistency (4-19%), no absolute stability, and either no or variable relative stability. Hair ECs/NAEs showed small to medium significant associations across the perinatal period within couples and parent-child dyads. Findings suggest hair ECs/NAEs during the perinatal period possess variable stability in adults, albeit more stability in fathers than mothers in this time. This highlights the need to further investigate factors associated with changes in hair ECs/NAEs across time. The first two years of life may be a dynamic phase for the endocannabinoid system in children, potentially characterized by complex within-family correspondence that requires further systematic investigation.

Longitudinal Assessment of Hair Cortisol as a Predictor of Psychological Symptoms During COVID-19.

BACKGROUND: There is a lack of evidence regarding enduring psychoneuroendocrine changes following an initial traumatic event, particular in the presence of an ongoing stressor. The coronavirus pandemic presents an opportunity to explore this matter. Consequently, the purpose of the present study was to investigate the impact of the ongoing pandemic (2021) on individuals, who experienced a first-time motor vehicle crash (MVC) at least 6 years earlier. To this end, we hypothesized that hair cortisol concentrations (HCC) following a first-time traumatic event positively predict symptoms of depression. METHOD: We investigated N = 69 individuals (18 - 65 yrs.), who were victims of a MVC during 2010 - 2014. Hair strands were collected 10 days (t1) and 3 months after the MVC (t2), as well during the pandemic in 2021 (t3). To assess symptoms of depression, the participants filled out the Beck Depression Inventory at t1 - t3 and were additionally interviewed (Structured Clinical Interview for DSM-IV Axis I) at t1 and t2. Exclusion criteria conveyed a lifetime or acute mental disorder (incl. past trauma exposure). RESULTS: Elevated pre-pandemic HCC following adversity (i.e., MVC) significantly predicted symptoms of depression in adults during the coronavirus pandemic (BDI: ß =.44, p =.010, R2 =.20), even after controlling for confounders. HCC significantly decreased over time, while in average psychological symptoms remained consistent. CONCLUSION: Cortisol dysregulation in the past presents an enduring vulnerability to ongoing stress. In this regard, vulnerable groups may benefit from preventive measures. This finding validates the predictive power of HCC and extended past evidence in this regard, at the same time reinforcing the concept of the diathesis-stress model.

Hair glucocorticoids during pregnancy in the context of trauma exposure and their predictive value for the development of childbirth-related posttraumatic stress disorder symptoms.

BACKGROUND: Childbirth-related posttraumatic stress disorder (CB-PTSD) is gaining attention as a mental disorder with negative sequela for mothers and their offspring. Maternal trauma history is a well-known vulnerability factor for CB-PTSD symptoms (CB-PTSS). Furthermore, alterations of the hypothalamus-pituitary-adrenal axis have been linked to both trauma exposure and PTSD development. Hence, we investigated whether trauma history was associated with long-term glucocorticoid (GC) levels during pregnancy and their predictive role for CB-PTSS. Further, we examined whether GCs act as a mediator in the relationship between trauma history and CB-PTSS and whether this was moderated by the subjective birth experience. METHODS: 212 women participating in the prospective cohort study DREAMHAIR provided hair samples for quantification of long-term integrated cortisol and cortisone levels prior to their anticipated birth date accompanied by measures of trauma history. CB-PTSS and subjective birth experience were assessed two months postpartum. FINDINGS: Trauma history predicted elevated hair cortisol and hair cortisone during the third trimester of pregnancy, however associations did not remain significant when Bonferroni correction due to multiple testing was applied. Trauma history also predicted higher CB-PTSS. Hair GC levels during pregnancy neither predicted CB-PTSS two months after birth nor mediated the relationship between trauma history and CB-PTSS. The subjective birth experience moderated the relationship of hair cortisol and cortisone with CB-PTSS. CONCLUSION: Our data suggest that a history of trauma contributes to a higher risk to develop CB-PTSS and elevated long-term GC levels during the third pregnancy trimester. Further, the predictive role of hair cortisol and cortisone levels for CB-PTSS may depend on subjective birth experience. This highlights the need to consider the latter in future investigations when examining the role of stress-related biomarkers in more severely affected samples.

DNA methylation profiles within the serotonin transporter gene moderate the association of 5-HTTLPR and cortisol stress reactivity.

The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been implicated in moderating vulnerability to stress-related psychopathology upon exposure to environmental adversity. A recent meta-analysis suggests a potential biological pathway conveying genotype-dependent stress sensitivity by demonstrating a small, but significant association of 5-HTTLPR and cortisol stress reactivity. An arguably more potent approach to detect larger effects when investigating the 5-HTTLPR stress sensitivity hypothesis is to account for both genetic and epigenetic variation in the serotonin transporter gene (SLC6A4). Here, we applied this approach in an experimental setting. Two hundred healthy adults were exposed to a laboratory stressor (Trier Social Stress Test) and cortisol response patterns were assessed as a function of 5-HTTLPR and DNA methylation profiles in SLC6A4. Specifically, we analyzed 83 CpG sites within a 799-bp promoter-associated CpG island of SLC6A4 using a highly sensitive bisulfite pyrosequencing method. Our results suggest that SLC6A4 methylation levels significantly moderate the association of 5-HTTLPR and cortisol stress reactivity. For individuals displaying low levels of SLC6A4 methylation, the S allele relates to increased cortisol stress reactivity in a dose-dependent fashion accounting for 7-9% of the variance in the endocrine stress response. By contrast, no such effect occurred under conditions of high SLC6A4 methylation, indicating that epigenetic changes may compensate for genotype-dependent differences in stress sensitivity. Studying epigenetic markers may advance gene-environment interaction research on 5-HTTLPR as they possibly capture the net effects of environmental influences relevant for stress-related phenotypes under serotonergic control.