Katharina Schury

Biological memory of childhood maltreatment - current knowledge and recommendations for future research

Child maltreatment (CM) not only has detrimental and lifelong psychological consequences, but also can lead to lasting alterations in core physiological systems—a biological memory of CM. Furthermore, some of these alterations might even be transmitted to the next generation. This article describes current knowledge about the effects of CM on the stress system (i.e., the hypothalamus–pituitary–adrenal axis), on cellular aging (i.e., telomere length and telomerase activity), and on the immune system. Furthermore, we want to initiate research on the question of transmission of the described physiological alterations subsequent to CM to the next generation—possibly through epigenetic imprinting. As diverse neurobiological factors and epigenetics are closely linked, these different research fields should join forces to gain a deeper understanding of the biological determinants and sequelae of CM and its transmission.

Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress.

The experience of maltreatment during childhood is associated with chronic low-grade inflammation in adulthood. However, the molecular mechanisms underlying this pro-inflammatory phenotype remain unclear. Mitochondria were recently found to principally coordinate inflammatory processes via both inflammasome activation and inflammasome-independent pathways. To this end, we hypothesized that alterations in immune cell mitochondrial functioning and oxidative stress might be at the interface between the association of maltreatment experiences during childhood and inflammation. We analyzed pro-inflammatory biomarkers (levels of C-reactive protein, cytokine secretion by peripheral blood mononuclear cells (PBMC) in vitro, PBMC composition, lysophosphatidylcholine levels), serum oxidative stress levels (arginine:citrulline ratio, l-carnitine and acetylcarnitine levels) and mitochondrial functioning (respiratory activity and density of mitochondria in PBMC) in peripheral blood samples collected from 30 women (aged 22-44years) with varying degrees of maltreatment experiences in form of abuse and neglect during childhood. Exposure to maltreatment during childhood was associated with an increased ROS production, higher levels of oxidative stress and an increased mitochondrial activity in a dose-response relationship. Moreover, the increase in mitochondrial activity and ROS production were positively associated with the release of pro-inflammatory cytokines by PBMC. Decreased serum levels of lysophosphatidylcholines suggested higher inflammasome activation with increasing severity of child maltreatment experiences. Together these findings offer preliminary evidence for the association of alterations in immune cell mitochondrial functioning, oxidative stress and the pro-inflammatory phenotype observed in individuals with a history of maltreatment during childhood. The results emphasize that the early prevention of child abuse and neglect warrants more attention, as the experience of maltreatment during childhood might have life-long consequences for physical health.

Alterations of hair cortisol and dehydroepiandrosterone in mother-infant-dyads with maternal childhood maltreatment

BackgroundChild maltreatment (CM) has severe effects on psychological and physical health. The hypothalamic-pituitary-adrenal (HPA) axis, the major stress system of the body, is dysregulated after CM. The analysis of cortisol and dehydroepiandrosterone (DHEA) in scalp hair presents a new and promising methodological approach to assess chronic HPA axis activity. This study investigated the effects of CM on HPA axis activity in the last trimester of pregnancy by measuring the two important signaling molecules, cortisol and DHEA in hair, shortly after parturition. In addition, we explored potential effects of maternal CM on her offspring’s endocrine milieu during pregnancy by measuring cortisol and DHEA in newborns’ hair.MethodsCM was assessed with the Childhood Trauma Questionnaire (CTQ). Cortisol and DHEA were measured in hair samples of 94 mothers and 30 newborns, collected within six days after delivery. Associations of maternal CM on her own and her newborn’s cortisol as well as DHEA concentrations in hair were analyzed with heteroscedastic regression models.ResultsHigher CM was associated with significantly higher DHEA levels, but not cortisol concentrations in maternal hair. Moreover, maternal CM was positively, but only as a non-significant trend, associated with higher DHEA levels in the newborns’ hair.ConclusionsResults suggest that the steroid milieu of the mother, at least on the level of DHEA, is altered after CM, possibly leading to non-genomic transgenerational effects on the developing fetus in utero. Indeed, we observed on an explorative level first hints that the endocrine milieu for the developing child might be altered in CM mothers. These results need extension and replication in future studies. The measurement of hair steroids in mothers and their newborns is promising, but more research is needed to better understand the effects of a maternal history of CM on the developing fetus.

Childhood maltreatment, postnatal distress and the protective role of social support

The postpartum period is a vulnerable period for women with a history of childhood maltreatment. This study investigated the association between childhood maltreatment and postnatal distress three months postpartum and examined the role of social support provided by different sources (intimate partner, parents, parents-in-law, and friends). Analyses are based on N=66 women, who were screened for maltreatment experiences shortly after parturition with the Childhood Trauma Questionnaire. Their levels of postnatal distress (symptoms of depression, anxiety, and stress; assessed with the Hospital Anxiety and Depression Scale and the 4-Item version of the Perceived Stress Scale) and postpartum social support (measured with the Postpartum Social Support Questionnaire) were assessed three months postpartum. Adjusting for educational level and the experience of a recent stressful event, childhood maltreatment was directly associated with higher levels of postnatal distress. Social support provided by friends moderated this association in a heteroscedastic regression analysis. No moderating effect was observed for support provided by the own parents, the intimate partner, or parents-in-law. The association between childhood maltreatment and postnatal distress was not mediated by social support. Additional analyses revealed no main, moderating, or mediating effects of satisfaction with support. Results suggest that support provided by friends may promote resilience during the postpartum period in women with a history of childhood maltreatment. Efforts to better understand the role of postpartum support and mechanisms that may enhance a mothers ability to develop and maintain supportive friendships may be promising for guiding preventive interventions.

Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers

Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the “hormone of affiliation” and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants (p = 0.004) and cortisol decreased in the significant majority of 73% participants (p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as well as males and include a control stimulus condition.

Child Maltreatment Is Associated with a Reduction of the Oxytocin Receptor in Peripheral Blood Mononuclear Cells

Background: Child maltreatment (CM) and attachment experiences are closely linked to alterations in the human oxytocin (OXT) system. However, human data about oxytocin receptor (OXTR) protein levels are lacking. Therefore, we investigated oxytocin receptor (OXTR) protein levels in circulating immune cells and related them to circulating levels of OXT in peripheral blood. We hypothesized reduced OXTR protein levels, associated with both, experiences of CM and an insecure attachment representation. Methods: OXTR protein expressions were analyzed by western blot analyses in peripheral blood mononuclear cells (PBMC) and plasma OXT levels were determined by radioimmunoassay (RIA) in 49 mothers. We used the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Attachment representations (secure vs. insecure) were classified using the Adult Attachment Projective Picture System (AAP) and levels of anxiety and depression were assessed with the German version of the Hospital Depression and Anxiety scale (HADS-D). Results: CM-affected women showed significantly lower OXTR protein expression with significantly negative correlations between the OXTR protein expression and the CTQ sum score, whereas plasma OXT levels showed no significant differences in association with CM. Lower OXTR protein expression in PBMC were particularly pronounced in the group of insecurely attached mothers compared to the securely attached group. Anxiety levels were significantly higher in CM-affected women. Conclusion: This study demonstrated a significant association between CM and an alteration of OXTR protein expression in human blood cells as a sign for chronic, long-lasting alterations in this attachment-related neurobiological system.

High prevalence of posttraumatic stress in patients with primary hypertension

OBJECTIVE Posttraumatic stress disorder (PTSD) is associated with a higher rate of arterial hypertension. However, data about prevalence rates of PTSD in patients suffering from arterial hypertension as well as the relation to blood pressure (BP) control are lacking. METHODS We recruited 145 patients with primary hypertension from March to November 2012 at the cardiologic outpatient clinic at Ulm University Medical Center. Symptoms of PTSD (assessed with the Posttraumatic Diagnostic Scale), perceived stress (Perceived Stress Scale; Trier Inventory for Chronic Stress), depression and anxiety (Hospital Anxiety and Depression Scale) were assessed by self-report. Office BP was measured and medical data were collected. RESULTS Criteria for a full PTSD syndrome were met by 13 patients (9%). Posttraumatic stress was higher in the group of patients with controlled (M=10.9, S.D.=9.8) than in those with uncontrolled hypertension (M=3.9, S.D.=5.4; P<.001). In linear regression, only status of hypertension control (beta=.39, P<.001) predicted posttraumatic stress significantly, even after controlling for important cofactors. CONCLUSIONS PTSD is highly prevalent in hypertensive patients, especially in those with controlled hypertension. An explaining mechanism could be the higher use of health care by patients suffering from PTSD. The mental needs of these patients should be focused in addition to the well-established somatic care.

Altered hair endocannabinoid levels in mothers with childhood maltreatment and their newborns

The endocannabinoid (EC) system possesses anti-inflammatory properties and seems to be altered in trauma-exposed individuals. In an intergenerational approach, this study investigated the link between childhood maltreatment (CM) experiences and alterations in the EC system. Hair samples of N = 142 mothers and N = 91 newborns were analyzed, retrospectively assessing EC regulation during the last trimester of pregnancy with four ECs: 1-arachidonoylglycerol (1-AG), N-oleoylethanolamide (OEA), N-stearoylethanolamide (SEA), and N-palmitoylethanolamide (PEA). Compared to mothers without CM, hair of mothers with CM showed significantly higher levels of 1-AG and lower levels of SEA. Newborns of mothers with CM exhibited higher levels of 1-AG and OEA. Furthermore, the higher the severity of maternal CM, the lower were maternal SEA levels and the higher neonatal OEA levels. Findings indicate altered EC levels during the last trimester of pregnancy in mothers with CM and their developing fetus, highlighting potential intergenerational effects from one generation to the other.

The involvement of mitochondria in chronic low-grade inflammation associated with maltreatment experiences during childhood

Experiencing maltreatment, abuse and/or neglect during childhood (CM) is associated with adverse health outcomes later in life. A state of chronic low-grade inflammation and alterations in inflammatory processes were suggested to be involved in the high prevalence of secondary diseases observed with CM. The molecular mechanisms underlying the establishment of this pro-inflammatory phenotype remain, however, largely unknown. On a cellular level, mitochondria were recently found to be not only the main energy suppliers of human cells, but also key regulators of inflammatory processes. We therefore analyzed in a study cohort of 30 women with varying degrees of CM experiences, whether mitochondrial activity was altered in immune cells and was associated with increased levels of inflammation. With increasingly severe CM experiences, study participants displayed higher levels of endogenous, bioactive molecules linked to oxidative stress and an increased immune cell mitochondrial activity, which was associated with a higher secretion of the pro-inflammatory cytokines IL-1beta, IL-6, and TNF-alpha. Together these data support the hypothesis that alterations in immune cell mitochondrial functioning might be at the interface between the association of CM experiences and a state of chronic low-grade inflammation that persists until adulthood. The present findings further emphasize that the early prevention of child maltreatment, abuse and neglect warrants more attention, as affected individuals suffer not only from life-long consequences for mental, but also for physical health.