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Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes.

ABSTRACT: In this investigation, gene-environment-gender interaction effects in predicting child borderline personality disorder symptomatology among maltreated and nonmaltreated low-income children (N = 1,051) were examined. In the context of a summer research camp, adult-, peer-, and self-report assessments of borderline precursor indicators were obtained, as well as child self-report on the Borderline Personality Features Scale for Children. Genetic variants of the oxytocin receptor genotype and the FK506 binding protein 5 gene CATT haplotype were investigated. Children who self-reported high levels of borderline personality symptomatology were differentiated by adults, peers, and additional self-report on indicators of emotional instability, conflictual relationships with peers and adults, preoccupied attachment, and indicators of self-harm and suicidal ideation. Maltreated children also were more likely to evince many of these difficulties relative to nonmaltreated children. A series of analyses of covariance, controlling for age and ancestrally informative markers, indicated significant Maltreatment × Gene × Gender three-way interactions. Consideration of the maltreatment parameters of subtype, onset, and recency expanded understanding of variation among maltreated children. The three-way interaction effects demonstrated differential patterns among girls and boys. Among girls, the gene-environment interaction was more consistent with a diathesis-stress model, whereas among boys a differential-sensitivity interaction effect was indicated. Moreover, the genetic variants associated with greater risk for higher borderline symptomatology, dependent on maltreatment experiences, were opposite in girls compared to boys. The findings have important implications for understanding variability in early predictors of borderline personality pathology.

SUBMITTER: Cicchetti D

PROVIDER: S-EPMC4123548 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes.

Cicchetti Dante D Rogosch Fred A FA Hecht Kathryn F KF Crick Nicki R NR Hetzel Susan S

Development and psychopathology 20140801 3

In this investigation, gene-environment-gender interaction effects in predicting child borderline personality disorder symptomatology among maltreated and nonmaltreated low-income children (N = 1,051) were examined. In the context of a summer research camp, adult-, peer-, and self-report assessments of borderline precursor indicators were obtained, as well as child self-report on the Borderline Personality Features Scale for Children. Genetic variants of the oxytocin receptor genotype and the FK ...[more]

PMID: 25047302

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Project description:BackgroundBorderline personality disorder (BPD) is a severe mental disorder, characterized by pronounced instability in emotions, self-image, and interpersonal relationships. Experiences of childhood maltreatment are among the risk factors for BPD. While self-damaging and aggressive acts often occur, not every person with the disorder shows markedly dysregulated behaviour. Internalized symptoms, such as shame, loneliness, and self-disgust tend to be more pervasive and persist after clinical remission.ObjectiveHere we investigated associations between BPD symptom severity, childhood maltreatment, and emotion regulation difficulties. We further explored if the Borderline Symptom List (BSL) could potentially be used to differentiate between internalized symptoms (intrapsychic strain) and externalized symptoms (dysregulated behaviours) in future research.Method187 women with at least mild BPD symptoms (65% having a diagnosis of BPD) completed the BSL 23 including its 11-item supplement (BSL-S), the Childhood Trauma Questionnaire (CTQ), and Difficulties in Emotion Regulation Scale (DERS). Participants further underwent a semi-structured clinical interview to assess BPD criteria (International Personality Disorder Examination, IPDE). Multivariate models and regression-based bootstrapping analyses were performed to test direct and indirect effects.ResultsChildhood trauma severity, especially emotional abuse, positively predicted BPD symptom severity. A significant indirect effect through emotion regulation difficulties was found (k2=.56). When exploring associations with BPD criteria (IPDE), the BSL-23 mean significantly correlated with separation anxiety, identity and mood problems, chronic emptiness, suicidal ideation, and dissociation, while the BSL-S correlated with self-harming impulsive behaviour and anger outbursts.ConclusionsFindings complement previous research, highlighting the role of childhood maltreatment and emotion regulation difficulties in BPD. While our findings need to be seen as preliminary and interpreted with caution, they suggest that the BSL may be used to differentiate between internalized symptoms and behavioural expressions of BPD in future research. Such a distinction might help to deepen the understanding of this complex heterogenous disorder.

Project description:Sleep disorders, such as insomnia and nightmares, are commonly associated with Borderline Personality Disorder (BPD) in adulthood. Whether nightmares and sleep-onset and maintenance problems predate BPD symptoms earlier in development is unknown. We addressed this gap in the literature using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants included 6050 adolescents (51.4 % female) who completed the UK Childhood Interview for DSM-IV BPD at 11 to 12 years of age. Nightmares and sleep onset and maintenance problems were prospectively assessed via mother report when children were 2.5, 3.5, 4.8 and 6.8 years of age. Psychopathological (i.e., emotional temperament; psychiatric diagnoses; and emotional and behavioural problems) and psychosocial (i.e., abuse, maladaptive parenting, and family adversity) confounders were assessed via mother report. In logistic regressions, persistent nightmares (i.e., regular nightmares at 3 or more time-points) were significantly associated with BPD symptoms following adjustment for sleep onset and maintenance problems and all confounders (Adjusted Odds Ratio = 1.62; 95 % Confidence Interval = 1.12 to 2.32). Persistent sleep onset and maintenance problems were not significantly associated with BPD symptoms. In path analysis controlling for all associations between confounders, persistent nightmares independently predicted BPD symptoms (Probit co-efficient [β] = 0.08, p = 0.013). Emotional and behavioural problems significantly mediated the association between nightmares and BPD (β =0.016, p < 0.001), while nightmares significantly mediated associations between emotional temperament (β = 0.001, p = 0.018), abuse (β = 0.015, p = 0.018), maladaptive parenting (β = 0.002, p = 0.021) and subsequent BPD. These findings tentatively support that childhood nightmares may potentially increase the risk of BPD symptoms in early adolescence via a number of aetiological pathways. If replicated, the current findings could have important implications for early intervention, and assist clinicians in the identification of children at risk of developing BPD.

Project description:Childhood maltreatment is associated with lasting changes in neuroendocrine regulation, alterations in brain structure and function, and symptoms of "limbic irritability." Limbic irritability symptoms include somatic, sensory, and behavioral phenomena and may stem from increased excitatory neurotransmission following maltreatment. We tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability and that variation within the FK506 binding protein 5 gene (FKBP5), a gene involved in glucorticoid receptor functioning, moderates these effects. The sample consisted of high-risk, low-income women (N = 236) living in an inner-city environment. Child maltreatment, limbic irritability, and symptoms of depression and dissociation were measured cross-sectionally using self-report assessments. Haplotype analyses were conducted across four FKBP5 single nucleotide polymorphisms: rs3800373, rs9296158, rs1360870, and rs9470080. Path analysis using bootstrapping procedures was performed to test hypotheses regarding indirect and conditional indirect effects. We found significant indirect effects of maltreatment on depression (? = 0.088, p < .01) and dissociation (? = 0.105, p < .01) via limbic irritability. In addition, variation within FKBP5 moderated these significant indirect effects. For individuals with one to two copies of the CATT haplotype, the indirect effects of maltreatment on depression (? = 0.137, p < .01) and dissociation (? = 0.132, p < .01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: ? = 0.037, p > .05; dissociation: ? = 0.002, p > .05). These results add to the growing evidence that child maltreatment may lead to symptoms of internalizing psychopathology through its impact on the limbic system. In addition, this study revealed a potential role of FKBP5 gene variants in contributing to risk for limbic system dysfunction.

Project description:BackgroundChildhood maltreatment, such as severe emotional, physical, and sexual abuse and neglect, has been linked to impulse control problems and dysfunctional emotional coping. In borderline personality disorder (BPD), a history of childhood maltreatment may worsen difficulties in emotion regulation, which may in turn give rise to impulsive behaviours. The aim of this self-report study was to investigate associations between childhood maltreatment severity, emotion regulation difficulties, and impulsivity in women with BPD compared to healthy and clinical controls.MethodsSixty-one female patients with BPD, 57 clinical controls (CC, women with Attention Deficit Hyperactivity Disorder and/or Substance Use Disorder, without BPD), and 60 female healthy controls (HC) completed self-report scales on childhood trauma (Childhood Trauma Questionnaire, CTQ), difficulties in emotion regulation (Difficulties in Emotion Regulation Scale, DERS), and impulsivity (UPPS Impulsive Behaviour Scale). A conditional process analysis was performed to investigate whether emotion dysregulation statistically mediated the effect of childhood maltreatment severity on impulsivity depending on group (BPD vs. CC vs. HC).ResultsChildhood maltreatment, particularly emotional maltreatment, was positively associated with impulsivity and emotion regulation difficulties across all groups. Difficulties in emotion regulation statistically mediated the effect of childhood maltreatment on impulsivity in BPD, but not in the other groups.ConclusionIn the context of current conceptualizations of BPD and previous research, findings suggest that problems with emotion regulation may be related to a history of childhood maltreatment, which may in turn enhance impulsivity. Targeting emotion dysregulation in psychotherapy and discussing it in relation to childhood maltreatment can help decreasing impulsive behaviors in individuals with BPD. Given the correlational design of our study which does not allow causal conclusions, future studies have to employ prospective, experimental designs and include larger sample sizes to corroborate associations between childhood maltreatment, emotion dysregulation, and impulsivity.

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Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes.

Publications

Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes.

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