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Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

ABSTRACT: Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD.Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse.Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis.Variation in TPH1 may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors.

SUBMITTER: Wilson ST

PROVIDER: S-EPMC3241896 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

Wilson Scott T ST Stanley Barbara B Brent David A DA Oquendo Maria A MA Huang Yung-yu YY Haghighi Fatemeh F Hodgkinson Colin A CA Mann J John JJ

Psychiatric genetics 20120201 1

<h4>Introduction</h4>Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship betwee ...[more]

PMID: 21989108

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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.

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Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

Publications

Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

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