Study protocol for a multi-center RCT testing a group-based parenting intervention tailored to mothers with borderline personality disorder against a waiting control group (ProChild*-SP1)

Background/aims Borderline personality disorder (BPD) is a severe mental disorder characterized by an unstable sense of self, intense and rapidly changing affect, as well as impulsive and self-destructive behaviors. Interpersonal relationships of individuals with BPD are characterized by marked instability, a lack of dependability, and quick changes between love and hate. For children of individuals with BPD, this can lead to permanent stress and attachment insecurity and an increased risk of adverse physical and mental health development. To reduce dysfunctional parenting and improve positive parenting, and in turn, to promote healthy child development, a group intervention for mothers with BPD was developed. This study aims to evaluate this first disorder-specific parenting intervention for BPD in a randomized controlled trial. Method In a parallel-group, two-arm, randomized controlled trial, an initial N = 178 mothers diagnosed with BPD and their children aged 6 months to 6 years are assigned to either the parenting intervention or a waiting control group. If taking place, participants of both groups continue their regular treatment for BPD diagnosis (e.g., individual therapy, medication). The primary outcomes are changes in parenting from baseline (day 0) to post intervention (week 12) and follow-up (6 months after group intervention; month 9). The waiting control group can attend the group intervention at the end of all assessments. Participants allocated to the intervention group are expected to show improvement in their parenting and a reduction in child abuse potential. Maternal emotion regulation and mental distress are analyzed as secondary outcomes. Discussion Mothers with BPD may need tailored help when reporting difficulties raising their children. The first disorder-specific parenting intervention has been developed to close this gap. ProChild is part of a large government-supported consortium, which aims to investigate different aspects of abuse and maltreatment in childhood and adolescence

Why does early childhood deprivation increase the risk for depression and anxiety in adulthood? A developmental cascade model

Abstract Background: Using data from the English & Romanian Adoptees (ERA) study we recently reported that early time-lmited exposure to severe institutional deprivation is associated with early onset and persistent neurodevelopmental problems and later onset emotional problems. Here we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. Methods: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity , exposure to adverse life events and functioning in work and interpersonal relationships. Results: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity and emotional problems were inconclusive. Conclusions: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model

The OXTR Single-Nucleotide Polymorphism rs53576 Moderates the Impact of Childhood Maltreatment on Empathy for Social Pain in Female Participants: Evidence for Differential Susceptibility

Previous research has associated genetic variations of the oxytocin receptor with individual differences in human social behavior. Specifically, homozygous carriers of the G-allele of the single nucleotide polymorphism rs53576 have been reported to display more trust, empathy, and prosocial behavior and were less sensitive toward stress and maltreatment during childhood when compared to A-allele carriers. With regard to Borderline Personality Disorder (BPD), a psychiatric condition that is often associated with the experience of childhood adversity, it has been suggested that A-allele carriers are more vulnerable to developing psychopathological signs and symptoms. In the present study we investigated whether childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), affects empathy for somatic and psychological pain, and how this is moderated by genotype, in a sample of 302 individuals (148 of whom were diagnosed with BPD). We found a three-way interaction between genotype, group and pain condition. Posthoc comparisons revealed that patients with BPD carrying at least one A-allele, rated psychological pain as more intense compared to controls, whereas no difference between groups emerged in GG homozygotes. Moreover, a moderating effect of genotype appeared on the impact of childhood trauma on empathy for psychological pain. In addition, a positive correlation of CTQ scores and empathy appeared only in A-allele carriers (GA + AA), independent of diagnosis. Together, A-allele carriers, especially those with BPD, seemed to be responsive to the impact of adversity on empathy-for-pain, while GG homozygotes were not, which is compatible with the idea of differential susceptibility

Risk and protective factors of mental health in children in residential care: A nationwide study from Luxembourg

peer reviewedBackground: Children who grow up in residential care are at high risk for mental health problems. Existing studies have focused on negative mental health indicators and risk factors. There has been less emphasis on identifying protective factors, particularly those associated with positive mental health outcomes. Objective: This study explores positive and negative dimensions of mental health and their links to risk and protective factors in children who have experienced early adversity and trauma and have been placed in residential care. Participants and settings: Children aged 11 to 18 (N =264) were recruited from residential care homes in Luxembourg, a small, high-income European country. Methods: The children completed self-report questionnaires on mental health, perceived stress, school pressure, and participation. Residential care workers provided information on demographic factors, developmental and care history, and pre-care experiences of early adversity and trauma. Results: Confirmatory factor analysis indicated that subjective well-being, internalising problems, and externalising problems are separate yet interconnected components of mental health. Multiple Indicators Multiple Causes models showed that individual, contextual, and psychosocial predictors contribute differentially to positive and negative mental health outcomes. Conclusions: Using a national sample of children in residential care in Luxembourg, this research indicates that subjective well-being, internalising problems, and externalising problems are distinct but related aspects of mental health. ‘Child participation’ and ‘school pressure’ displayed strong links with positive mental health outcomes and may serve as a potential path for improving public health interventions for children in care.HER

The association between childhood maltreatment and empathic perspective taking is moderated by the 5-HTT linked polymorphic region: Another example of "differential susceptibility"

Previous research has suggested that the short (S)-allele of the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) may confer "differential susceptibility" to environmental impact with regard to the expression of personality traits, depressivity and impulsivity. However, little is known about the role of 5-HTTLPR concerning the association between childhood adversity and empathy. Here, we analyzed samples of 137 healthy participants and 142 individuals diagnosed with borderline personality disorder (BPD) focusing on the 5-HTTLPR genotype (S/L-carrier) and A/G SNP (rs25531), in relation to childhood maltreatment and empathy traits. Whereas no between-group difference in 5-HTTLPR genotype distribution emerged, the S-allele selectively moderated the impact of childhood maltreatment on empathic perspective taking, whereby low scores in childhood trauma were associated with superior perspective taking. In contrast, L-homozygotes seemed to be largely unresponsive to variation in environmental conditions in relation to empathy, suggesting that the S-allele confers "differential susceptibility". Moreover, a moderation analysis and tests for differential susceptibility yielded similar results when transcriptional activity of the serotonin transporter gene was taken into account. In conclusion, our findings suggest that the S-allele of the 5-HTTLPR is responsive to early developmental contingencies for "better and worse", i.e. conferring genetic plasticity, especially with regard to processes involving emotional resonance

Study protocol for a multi-center RCT testing a group-based parenting intervention tailored to mothers with borderline personality disorder against a waiting control group (ProChild*-SP1).

BACKGROUND/AIMS: Borderline personality disorder (BPD) is a severe mental disorder characterized by an unstable sense of self, intense and rapidly changing affect, as well as impulsive and self-destructive behaviors. Interpersonal relationships of individuals with BPD are characterized by marked instability, a lack of dependability, and quick changes between love and hate. For children of individuals with BPD, this can lead to permanent stress and attachment insecurity and an increased risk of adverse physical and mental health development. To reduce dysfunctional parenting and improve positive parenting, and in turn, to promote healthy child development, a group intervention for mothers with BPD was developed. This study aims to evaluate this first disorder-specific parenting intervention for BPD in a randomized controlled trial. METHOD: In a parallel-group, two-arm, randomized controlled trial, an initial N = 178 mothers diagnosed with BPD and their children aged 6 months to 6 years are assigned to either the parenting intervention or a waiting control group. If taking place, participants of both groups continue their regular treatment for BPD diagnosis (e.g., individual therapy, medication). The primary outcomes are changes in parenting from baseline (day 0) to post intervention (week 12) and follow-up (6 months after group intervention; month 9). The waiting control group can attend the group intervention at the end of all assessments. Participants allocated to the intervention group are expected to show improvement in their parenting and a reduction in child abuse potential. Maternal emotion regulation and mental distress are analyzed as secondary outcomes. DISCUSSION: Mothers with BPD may need tailored help when reporting difficulties raising their children. The first disorder-specific parenting intervention has been developed to close this gap. ProChild is part of a large government-supported consortium, which aims to investigate different aspects of abuse and maltreatment in childhood and adolescence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04169048 . Registered on Nov 19, 2019

No association between war-related trauma or PTSD symptom severity and epigenome-wide DNA methylation in Burundian refugees.

Background: War-related trauma is associated with varying posttraumatic stress disorder (PTSD) prevalence rates in refugees. In PTSD development, differential DNA methylation (DNAm) levels associated with trauma exposure might be involved in risk versus resilience processes. Studies investigating DNAm profiles related to trauma exposure and PTSD among refugees remain sparse.Objective: The present epigenome-wide association study investigated associations between war-related trauma, PTSD, and altered DNAm patterns in Burundian refugee families with 110 children and their 207 female and male caregivers.Method: War-related trauma load and PTSD symptom severity were assessed in structured clinical interviews with standardised instruments. Epigenome-wide DNAm levels were quantified from buccal epithelia using the Illumina EPIC beadchip.Results: Controlling for biological confounders, no significant epigenome-wide DNAm alterations associated with trauma exposure or PTSD were identified in children or caregivers (FDRs > .05). Co-methylated positions derived as modules from weighted gene correlation network analyses were not significantly associated with either war-related trauma experience in children or caregivers or with PTSD.Conclusions: These results do not provide evidence for altered DNAm patterns associated with exposure to war-related trauma or PTSD

Poverty, early care and stress reactivity in adolescence: findings from a prospective, longitudinal study in a low-middle income country

A considerable body of evidence suggests that early caregiving may affect the short-term functioning and longer-term development of the hypothalamic-pituitary adrenocortical (HPA) axis. Despite this, most research to date has been cross-sectional in nature or restricted to relatively short–term longitudinal follow-ups. More importantly, there is a paucity of research on the role of caregiving in low and middle income countries, where the protective effects of high quality care in buffering the child’s developing stress regulation systems may be crucial. In this paper, we report findings from a longitudinal study (N = 232) conducted in an impoverished peri-urban settlement in Cape Town, South Africa. We measured caregiving sensitivity and security of attachment in infancy and followed children up at age 13 years, when we conducted assessments of HPA axis reactivity, as indexed by salivary cortisol during the Trier Social Stress Test. The findings indicated that insecure attachment was predictive of reduced cortisol responses to social stress, particularly in boys, and that attachment status moderated the impact of contextual adversity on stress responses: secure children in highly adverse circumstances did not show the blunted cortisol response shown by their insecure counterparts. Some evidence was found that sensitivity of care in infancy was also associated with cortisol reactivity, but in this case insensitivity was associated with heightened cortisol reactivity, and only for girls. The discussion focuses on the potentially important role of caregiving in the long-term calibration of the stress system and the need to better understand the social and biological mechanisms shaping the stress response across development in low and middle income countries

No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder

DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD