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Gene expression profiles in relation to tension and dissociation in borderline personality disorder.

ABSTRACT: The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression. We conducted a whole blood gene expression profile analysis using quantitative PCR in 31 female inpatients with BPD. For each individual, two samples were drawn during a state of high tension and dissociation, while two samples were drawn at non-tension states. There was no association between gene expression and tension states. However, we could show that Interleukin-6 was positively correlated to dissociation scores, whereas Guanine nucleotide-binding protein G(s) subunit alpha isoforms, Mitogen-activated protein kinase 3 and 8, Guanine nucleotide-binding protein G(i) subunit alpha-2, Beta-arrestin-1 and 2, and Cyclic AMP-responsive element-binding protein were negatively correlated to dissociation. Our data point to a potential association of dissociation levels with the expression of genes involved in immune system regulation as well as cellular signalling/second-messenger systems. Major limitations of the study are the the possibly heterogeneous cell proportions in whole blood and the heterogeneous medication.

SUBMITTER: Schmahl C

PROVIDER: S-EPMC3741306 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Gene expression profiles in relation to tension and dissociation in borderline personality disorder.

Schmahl Christian C Arvastson Lars L Tamm Joseph A JA Bohus Martin M Abdourahman Aicha A Antonijevic Irina I

PloS one 20130812 8

The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression. We conducted a whole blood gene expression profile ana ...[more]

PMID: 23951008

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Project description:IntroductionDissociative symptoms are highly prevalent in patients with trauma-related disorders such as borderline personality disorder (BPD) and posttraumatic-stress disorder (PTSD), and also occur in patients with depressive disorders. Acute dissociative states are theorized to be stress-related, and some individuals experience recurring patterns of dissociation. The relationship between the intensity of dissociative episodes (trait-like dissociation) and acute dissociative states, however, is incompletely understood. In the present study, we investigated how levels of baseline (trait-like) dissociation relate to changes in dissociative states during a laboratory stress induction.MethodsOur female sample comprised 65 patients with BPD and/or PTSD, 84 patients with major depressive disorder (MDD) and 44 non-clinical controls (NCC). Baseline dissociation was assessed at the start of the study using the Dissociation Tension Scale past week version (DSS-7). All participants underwent the Trier Social Stress Test (TSST) and a placebo version (P-TSST). Before and after the TSST or P-TSST, state dissociation was assessed using the Dissociation Tension Scale acute (DSS-4). We used structural equation models to estimate changes in state dissociation items (somatoform dissociation, derealization, depersonalization, analgesia), and to test whether these changes relate to levels of baseline dissociation.ResultsWe found significant increases in all state dissociation items in response to the TSST in patients with BPD and/or PTSD and patients with MDD, but not in NCCs. Increases in somatoform dissociation and derealization during the TSST were significantly related to higher levels of baseline dissociation in patients with BPD and/or PTSD, but not in patients with MDD or NCCs. Results indicate no significant changes in state dissociation during the P-TSST.ConclusionOur results replicate earlier findings that patients with BPD and/or PTSD report higher levels of stress-related state dissociation than NCC and extend them to patients with MDD. In addition, our findings indicate that baseline levels of dissociation relate to stress-induced changes in state dissociation among patients with BPD and PTSD, but not patients with MDD. In clinical applications, measures of baseline dissociation could be used to facilitate the prediction and treatment of stress-related dissociative states in patients with BPD and/or PTSD.

Project description:BackgroundDrugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters.ObjectivesTo assess the effects of drug treatment in BPD patients.Search strategyWe searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field.Selection criteriaRandomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects.Data collection and analysisTwo authors selected trials, assessed quality and extracted data, independently.Main resultsTwenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes.Authors' conclusionsThe available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Project description:ObjectiveThere is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that "social pain," as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity.MethodTwenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity.ResultsHigher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala.DiscussionDespite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls.

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Gene expression profiles in relation to tension and dissociation in borderline personality disorder.

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Gene expression profiles in relation to tension and dissociation in borderline personality disorder.

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