An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.
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Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology. (+info)
Attentional mechanisms of borderline personality disorder.
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We consider whether disruption of a specific neural circuit related to self-regulation is an underlying biological deficit in borderline personality disorder (BPD). Because patients with BPD exhibit a poor ability to regulate negative affect, we hypothesized that brain mechanisms thought to be involved in such self-regulation would function abnormally even in situations that seem remote from the symptoms exhibited by these patients. To test this idea, we compared the efficiency of attentional networks in BPD patients with controls who were matched to the patients in having very low self-reported effortful control and very high negative emotionality and controls who were average in these two temperamental dimensions. We found that the patients exhibited significantly greater difficulty in their ability to resolve conflict among stimulus dimensions in a purely cognitive task than did average controls but displayed no deficit in overall reaction time, errors, or other attentional networks. The temperamentally matched group did not differ significantly from either group. A significant correlation was found between measures of the ability to control conflict in the reaction-time task and self-reported effortful control. (+info)
Fluvoxamine reduces responsiveness of HPA axis in adult female BPD patients with a history of sustained childhood abuse.
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The aim of the study is to test whether fluvoxamine affects the function of the hypothalamic pituitary adrenal (HPA) axis in female borderline (borderline personality disorder, BPD) patients with and without a history of sustained childhood abuse. Special attention is given to the presence of comorbid major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The HPA axis of 30 female BPD patients with (n = 17) and without (n = 13) a history of sustained childhood abuse was challenged with a combined dexamethasone and corticotropin releasing hormone test (DEX/CRH test) before and after 6 (n = 14) and 12 (n = 16) weeks of fluvoxamine treatment (150 mg/day). Both 6- and 12-week fluvoxamine treatments were associated with a significant and robust reduction of the adrenocorticotrophic hormone (ACTH) and cortisol response to the DEX/CRH test. The magnitude of the reduction was dependent on the presence of sustained childhood abuse, but not on the presence of comorbid MDD or PTSD: patients with a history of sustained childhood abuse showed the strongest reduction in ACTH and cortisol. In conclusion, Fluvoxamine treatment reduces the hyperresponsiveness of the HPA axis in BPD patients with a history of sustained childhood abuse. This effect is likely to be obtained in the first 6 weeks of treatment. (+info)
Dialectical behaviour therapy for women with borderline personality disorder: 12-month, randomised clinical trial in The Netherlands.
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BACKGROUND: Dialectical behaviour therapy (DBT) is widely considered to be a promising treatment for borderline personality disorder (BPD). However, the evidence for its efficacy published thus far should be regarded as preliminary. AIMS: To compare the effectiveness of DBT with treatment as usual for patients with BPD and to examine the impact of baseline severity on effectiveness. METHOD: Fifty-eight women with BPD were randomly assigned to either 12 months of DBT or usual treatment in a randomised controlled study. Participants were recruited through clinical referrals from both addiction treatment and psychiatric services. Outcome measures included treatment retention and the course of suicidal, self-mutilating and self-damaging impulsive behaviours. RESULTS: Dialectical behaviour therapy resulted in better retention rates and greater reductions of self-mutilating and self-damaging impulsive behaviours compared with usual treatment, especially among those with a history of frequent self-mutilation. CONCLUSIONS: Dialectical behaviour therapy is superior to usual treatment in reducing high-risk behaviours in patients with BPD. (+info)
'Still-face' interactions between mothers with borderline personality disorder and their 2-month-old infants.
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BACKGROUND: There is evidence that psychopathology in mothers may be associated with dysfunctional mother-infant interactions. AIMS: To investigate mother-infant relations when mothers have borderline personality disorder. METHOD: Eight mothers with borderline personality disorder and twelve mothers without psychiatric disorder were videotaped interacting with their 2-month-old infants in three successive phases of interaction: face-to-face play; an episode when the mother adopted a 'still face' and was unreactive; and a period when play interactions were resumed. The videotapes were rated by judges blind to the diagnostic group of the mother. RESULTS: The mothers with borderline personality disorder were more intrusively insensitive towards their infants. During the still-face period, their infants showed increased looking away and dazed looks. Following this, mother-infant interactions were less satisfying and their infants showed dazed looks and lowering of affect. CONCLUSIONS: The diagnosis of borderline personality disorder is associated with a particular pattern of mother-infant interaction. The infants' responses to the still-face challenge might suggest dysfunctional self-regulation, but the developmental significance remains to be assessed. (+info)
Dopamine dysfunction in borderline personality disorder: a hypothesis.
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Research on the biological basis of borderline personality disorder (BPD) has focused primarily on the serotonin model of impulsive aggression. However, there is evidence that dopamine (DA) dysfunction may also be associated with BPD. Pertinent research and review articles, identified by Medline searches of relevant topics, books, references from bibliographies, and conference proceedings from 1975 to 2003, were reviewed. Evidence of DA dysfunction in BPD derives from the efficacy of traditional and atypical antipsychotic agents in BPD, and from provocative challenges with amphetamine and methylphenidate of subjects with the disorder. In addition, human and animal studies indicate that DA activity plays an important role in emotion information processing, impulse control, and cognition. The results of this review suggest that DA dysfunction is associated with three dimensions of BPD, that is, emotional dysregulation, impulsivity, and cognitive-perceptual impairment. The main limitation of this hypothesis is that the evidence reviewed is circumstantial. There is no study that directly demonstrates DA dysfunction in BPD. In addition, the therapeutic effects of antipsychotic agents observed in BPD may be mediated by non-DA mechanisms of action. If the stated hypothesis is correct, DA dysfunction in BPD may result from genetic, developmental, or environmental factors directly affecting specific DA pathways. Alternatively, DA dysfunction in BPD may be a compensatory response to alterations in the primary neural systems that control emotion, impulse control, and cognition, and that are mediated by the brain's main neurotransmitters, glutamate, and GABA, or in one or more other neuromodulatory pathways such as serotonin, acetylcholine, and norepinephrine. (+info)
Attachment studies with borderline patients: a review.
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Clinical theorists have suggested that disturbed attachments are central to borderline personality disorder (BPD) psychopathology. This article reviews 13 empirical studies that examine the types of attachment found in individuals with this disorder or with dimensional characteristics of BPD. Comparison among the 13 studies is handicapped by the variety of measures and attachment types that these studies have employed. Nevertheless, every study concludes that there is a strong association between BPD and insecure attachment. The types of attachment found to be most characteristic of BPD subjects are unresolved, preoccupied, and fearful. In each of these attachment types, individuals demonstrate a longing for intimacy and--at the same time--concern about dependency and rejection. The high prevalence and severity of insecure attachments found in these adult samples support the central role of disturbed interpersonal relationships in clinical theories of BPD. This review concludes that these types of insecure attachment may represent phenotypic markers of vulnerability to BPD, suggesting several directions for future research. (+info)
Positron emission tomography of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without borderline personality disorder.
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Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders. (+info)