The Emerging Circadian Phenotype of Borderline Personality Disorder: Mechanisms, Opportunities and Future Directions.
Ontology highlight
ABSTRACT: Purpose of review
We review the recent evidence suggesting that circadian rhythm disturbance is a common unaddressed feature of borderline personality disorder (BPD); amelioration of which may confer substantial clinical benefit. We assess chronobiological BPD studies from a mechanistic and translational perspective and highlight opportunities for the future development of this hypothesis.Recent findings
The emerging circadian phenotype of BPD is characterised by a preponderance of comorbid circadian rhythm sleep-wake disorders, phase delayed and misaligned rest-activity patterns and attenuated amplitudes of usually well-characterised circadian rhythms. Such disturbances may exacerbate symptom severity, and specific maladaptive personality dimensions may produce a liability towards extremes in chronotype. Pilot studies suggest intervention may be beneficial, but development is limited. Endogenous and exogenous circadian rhythm disturbances appear to be common in BPD. The interface between psychiatry and chronobiology has led previously to novel efficacious strategies for the treatment of psychiatric disorders. We believe that better characterisation of the circadian phenotype in BPD will lead to a directed biological target for treatment in a condition where there is a regrettable paucity of accessible therapies.
SUBMITTER: McGowan NM
PROVIDER: S-EPMC8035096 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Bipolar disorder (BD) and borderline personality disorder (BPD) are two psychiatric disorders with overlapping features that can be challenging to separate diagnostically. Growing evidence suggests that circadian rhythm disturbances are associated with psychiatric illness, however circadian patterns of behaviour have not been elucidated in BPD or differentiated from BD. This study compared the circadian structure and timing of rest-activity patterns in BPD with BD and healthy volunteers. Participants with BD (N?=?31) and BPD (N?=?21) and healthy controls (HC, N?=?35) wore an actigraph on their non-dominant wrist for 28?day periods as part of the Automated Monitoring of Symptom Severity (AMoSS) study. Non-parametric circadian rhythm analysis of rest-activity patterns and cosinor analysis of distal temperature rhythms were conducted to elucidate circadian function between groups. Covariates controlled for included employment status, BMI and gender. Compared with HC and BD, individuals with BPD showed significantly delayed phase of night-time rest patterns ("L5 onset") (mean difference?=?1:47?h, P?<?0.001; mean difference?=?1:38?h, P?=?0.009, respectively), and relative to HC showed delayed daytime activity onset ("M10 onset") (mean difference?=?2:13?h, P?=?0.048) and delayed temperature phase (mean difference?=?1:22?h, P?=?0.034). These findings suggest that delayed circadian function may be a clinically important phenotype in individuals with BPD. Future work should interrogate the causality of this association and examine interventions which target delayed circadian function in the treatment of BPD.
| S-EPMC6702232 | biostudies-literature
Project description:Borderline personality disorder is a chronic psychiatric disorder characterized by marked impulsivity, instability of mood and interpersonal relationships, and suicidal behaviour that can complicate medical care. Identifying this diagnosis is important for treatment planning. Although the cause of borderline personality disorder is uncertain, most patients improve with time. There is an evidence base for treatment using both psychotherapy and psychopharmacology. The clinical challenge centres on managing chronic suicidality.
| S-EPMC558173 | biostudies-literature
Project description:BackgroundBorderline personality disorder (BPD) is a serious mental disorder characterized by marked interpersonal disturbances, including difficulties trusting others and volatile impressions of others' moral character, often resulting in premature relationship termination. We tested a hypothesis that moral character inference is disrupted in BPD and sensitive to democratic therapeutic community (DTC) treatment.MethodsParticipants with BPD (n = 43; 20 untreated and 23 DTC-treated) and control participants without BPD (n = 106) completed a moral inference task where they predicted the decisions of 2 agents with distinct moral preferences: the "bad" agent was more willing than the "good" agent to harm others for money. Periodically, participants rated their subjective impressions of the agent's moral character and the certainty of those impressions. We fit a hierarchical Bayesian learning model to participants' trialwise predictions to describe how beliefs about the morality of the agents were updated by new information.ResultsThe computational mechanisms of moral inference differed for patients with untreated BPD relative to matched control participants and patients with DTC-treated BPD. In patients with BPD, beliefs about harmful agents were more certain and less amenable to updating relative to both control participants and participants who were treated with DTC.ConclusionsThe findings suggest that DTC may help the maintenance of social relationships in BPD by increasing patients' openness to learning about adverse interaction partners. The results provide mechanistic insights into social deficits in BPD and demonstrate the potential for combining objective behavioral paradigms with computational modeling as a tool for assessing BPD pathology and treatment outcomes.
| S-EPMC7718209 | biostudies-literature
Project description: Not available
| S-EPMC3503902 | biostudies-literature
Project description:Purpose of Review:Variation in the monoamine oxidase A (MAO-A) gene and MAO-A enzyme levels have been linked to antisocial behavior and aggression in clinical and non-clinical populations. Here, we provide an overview of the genetic, epigenetic, and neuroimaging research that has examined MAO-A structure and function in antisocial personality disorder (ASPD) and borderline personality disorder (BPD). Recent Findings:The low-activity MAO-A variable nucleotide tandem repeat genetic polymorphism has shown a robust association with large samples of violent and seriously violent offenders, many of whom had ASPD. A recent positron emission tomography (PET) study of ASPD similarly revealed low MAO-A density in brain regions thought to contribute to the psychopathology of the condition. By contrast, PET has also demonstrated that brain MAO-A levels are increased in BPD and that they relate to symptoms of low mood and suicidality. Summary:Candidate gene studies have produced the most compelling evidence connecting MAO-A genetic variants to both ASPD and BPD. Still, conflicting results abound in the literature, making it highly unlikely that ASPD or BPD is related to a specific MAO-A genetic variant. Future research should strive to examine how MAO-A genotypes interact with broad-spectrum environmental influences to produce brain endophenotypes that may ultimately become tractable targets for novel treatment strategies.
| S-EPMC5846806 | biostudies-literature
Project description:Borderline personality disorder (BPD) is a complex psychiatric disease with an increased impact in the last years. While the diagnosis and therapy are well established, little is known on the pathogenesis of borderline personality disorder. Previously, a significant increase in DNA methylation of relevant neuropsychiatric genes in BPD patients has been reported. In our study we performed genome wide methylation analysis and revealed specific CpG sites that exhibited increased methylation in 26 BPD patients compared to 11 healthy controls. Bead chip technology and quantitative bisulfite pyrosequencing showed a significantly increased methylation at CpG sites of APBA2 (1.1 fold) and APBA3 (1.1 fold), KCNQ1 (1.6 fold), MCF2 (1.1 fold) and NINJ2 (1.2 fold) in BPD patients. For the CpG sites of GATA4 an increase in DNA methylation was observed, but was only significant in the bead chip assay. Moreover genome wide methylation levels of blood samples of BPD patients and control samples are similar. In summary, our results show a significant 1.26 fold average increase in methylation at the analyzed gene associated CpG sites in the blood of BPD patients compared to controls samples (p<0.001). This data may provide new insights into epigenetic mechanisms underlying the pathogenesis of BPD.
2014-02-01 | GSE52222 | GEO
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).
| S-EPMC4169794 | biostudies-literature
Project description:According to several studies, the onset of the Borderline Personality Disorder (BPD) depends on the combination between genetic and environmental factors (GxE), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. We have searched for studies reporting possible alterations in several biological processes and brain morphological features in relation to childhood trauma experiences and to BPD. We have also looked for epigenetic mechanisms as they could be mediators of the effects of childhood trauma in BPD vulnerability.We prove the role of alterations in Hypothalamic-Pituitary-Adrenal (HPA) axis, in neurotrasmission, in the endogenous opioid system and in neuroplasticity in the childhood trauma-associated vulnerability to develop BPD; we also confirm the presence of morphological changes in several BPD brain areas and in particular in those involved in stress response. Not so many studies are available on epigenetic changes in BPD patients, although these mechanisms are widely investigated in relation to stress-related disorders. A better comprehension of the biological and epigenetic mechanisms, affected by childhood trauma and altered in BPD patients, could allow to identify "at high risk" subjects and to prevent or minimize the development of the disease later in life.
| S-EPMC5472954 | biostudies-literature
Project description:Borderline personality disorder (BPD) patients, when in crisis, are frequent visitors of emergency departments (EDs). When these patients exhibit symptoms such as aggressiveness, impulsivity, intense anxiety, severe depression, self-harm, and suicidal attempts or gestures, diagnosis, and treatment of the BPD becomes challenging for ED doctors. This review will, therefore, outline advice to physicians and health-care providers who face this challenging patient population in the EDs. Crisis intervention should be the first objective of clinicians when dealing with BPD in the emergency. For the patients with agitation, symptom-specific pharmacotherapy is usually recommended, while for non-agitated patients, short but intensive psychotherapy especially dialectical behavior therapy (DBT) has a positive effect. Although various psychotherapies, either alone or integrated, are preferred modes of treatment for this group of patients, the effects of psychotherapies on BPD outcomes are small to medium. Proper risk management along with developing a positive attitude and empathy toward these patients will help them in normalizing in an emergency setting after which treatment course can be decided.
| S-EPMC5543278 | biostudies-other
Project description:The present paper discusses how cultural context can be used as an essential tool in the diagnosis of mental disorders as well as in segregating individuals with normal or abnormal personality functioning. Further, such information about the culture can be used to diagnose individuals specifically with borderline personality disorder (BPD). BPD is a mental illness marked by impulsivity and instability in interpersonal relationships, moods, and self-image. We discuss how culture shapes patterns of behavior in the individual with BPD. An extensive review of manifestation of BPD in eastern countries suggests that culture and social norms are the two crucial factors, which can differentiate normal and abnormal behavioral patterns in BPD. For example, the social norms shape and give directions to our interpersonal functioning, emotions are experienced within the cultural context and expressed accordingly, and self is a reflection and representation of one's culture. Hence, these constructs of BPD (such as interpersonal functioning, emotions, and self) indicate that they are experienced differently in different cultures and vary on the continuum of normal to abnormal personality functioning. The cultural manifestation of BPD helps to understand the specific profile of the three constructs of BPD in an eastern culture like India. A synthesis of studies on prevalence, development, and symptom presentation of BPD in the Indian context is emphasized to support the personality functioning within the constructs of BPD. The literature review indicates that BPD research in India is based only on a few cases and a tiny sample of such patients. However, studies on BPD in the cultural context are minimal and incomprehensive. Hence, it suggests the importance of more empirical studies concerning the appropriate diagnosis of BPD within the cultural context of India.
| S-EPMC7186391 | biostudies-literature