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Adamczyk PM, Shaw A, Morella IM, More L. Neurobiology, molecular pathways, and environmental influences in antisocial traits and personality disorders. Neuropharmacology 2025; 269:110322. [PMID: 39864585 DOI: 10.1016/j.neuropharm.2025.110322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 12/17/2024] [Accepted: 01/20/2025] [Indexed: 01/28/2025]
Abstract
Personality disorders (PDs) are psychiatric conditions characterized by enduring patterns of cognition, emotion, and behaviour that deviate significantly from cultural norms, causing distress or impairment. The aetiology of PDs is complex, involving both genetic and environmental factors. Genetic studies estimate the heritability of PDs at 30%-60%, implicating genes involved in neurotransmitter regulation, such as those for serotonin transporters and dopamine receptors. Environmental factors, including childhood trauma and chronic stress, interact with genetic predispositions to induce epigenetic modifications like DNA methylation and histone modifications, contributing to PD development. Neurobiological research has identified structural and functional abnormalities in brain regions related to emotional regulation and social cognition, such as the amygdala, prefrontal cortex, and limbic system. These abnormalities are linked to impaired emotion processing and interpersonal functioning in PDs. This review focuses on how environmental factors shape maladaptive behaviours and endophenotypes central to many PDs. It explores the interaction between the Ras-ERK, p38, and mTOR molecular pathways in response to environmental stimuli, and examines the role of oxidative stress and mitochondrial metabolism in these processes. Also reviewed are various types of PDs and existing animal models that replicate key endophenotypes, highlighting changes in neurotransmitters and neurohormones. Identifying molecular biomarkers can lead to the development of "enviromimetic" drugs, which mimic environmental influences to activate molecular pathways, facilitating targeted, personalized treatments based on the molecular profiles of individuals with PDs. Ultimately, understanding the molecular mechanisms of PDs promises to enhance diagnostic accuracy, prognosis, and therapeutic outcomes for affected individuals.
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Affiliation(s)
- Patryk M Adamczyk
- School of Pharmacy and Biomedical Sciences, The University of Central Lancashire, Preston, UK
| | - Andrew Shaw
- Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
| | - Ilaria M Morella
- University of Pavia, Department of Biology and Biotechnology "Lazzaro Spallanzani", Pavia, Italy; Cardiff University, School of Medicine, Division of Psychological Medicine and Clinical Neurosciences, Cardiff, UK.
| | - Lorenzo More
- School of Pharmacy and Biomedical Sciences, The University of Central Lancashire, Preston, UK.
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2
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Pardossi S, Cuomo A, Koukouna D, Pinzi M, Firenzuoli B, Fagiolini A. Methylphenidate in Borderline Personality Disorder: Assessing Its Therapeutic Potential and Limitations. Life (Basel) 2025; 15:380. [PMID: 40141725 PMCID: PMC11944194 DOI: 10.3390/life15030380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/22/2025] [Accepted: 02/27/2025] [Indexed: 03/28/2025] Open
Abstract
Impulsivity is increasingly recognized as a transdiagnostic feature that spans multiple psychiatric disorders, including borderline personality disorder (BPD), bipolar disorder, and substance use disorders. In BPD, impulsive behaviors manifest as substance misuse, risky sexual activity, self-injury, and other maladaptive patterns. This review article updates the clinical and preclinical literature to explore the biological and psychological bases of impulsivity in BPD and considers whether methylphenidate (MPH) can be used as a treatment in this context. Although no medication is specifically approved for BPD, limited evidence from patients with comorbid BPD and attention-deficit/hyperactivity disorder (ADHD) indicates that MPH may reduce impulsivity and improve key symptoms. In addition, real-world data indicate that MPH may be associated with better outcomes and a lower risk of suicidal behaviors in patients with BPD. Nevertheless, such evidence remains scant, particularly among those with a primary diagnosis of BPD without a diagnosis of ADHD. Larger, methodologically rigorous studies are needed to clarify the efficacy and safety of MPH in targeting impulsivity within this population. An improved understanding of dopaminergic mechanisms may eventually shed light on MPH's therapeutic role in BPD, although current data remain preliminary. Overall, recognizing impulsivity as a core symptom rather than focusing exclusively on diagnostic boundaries may facilitate more tailored and effective interventions for BPD.
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Affiliation(s)
- Simone Pardossi
- Department of Molecular Medicine, School of Medicine, University of Siena, 53100 Siena, Italy; (A.C.); (D.K.); (M.P.); (B.F.); (A.F.)
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Uzar M, Dmitrzak-Węglarz M, Słopień A. The Role of Oxytocin and Vasopressin in People with Borderline Personality Disorder: A Closer Look at Adolescents. Int J Mol Sci 2024; 25:12046. [PMID: 39596113 PMCID: PMC11593878 DOI: 10.3390/ijms252212046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024] Open
Abstract
Borderline personality disorder constitutes a significant medical challenge. Despite the fact that its occurrence among adolescents is currently attracting increasing interest from both clinicians and researchers, there is still insufficient data on this phenomenon. The etiology and maintenance of borderline personality disorder are not yet fully comprehended. Neuropeptides, including oxytocin and vasopressin, are considered to be involved in the development of this condition. The mechanism behind the actions of these neurohormones requires further investigation. Our work aims to collect and analyze the available research and existing hypotheses on the role of oxytocin and vasopressin in people with borderline personality disorder, with special attention drawn to adolescents suffering from this condition.
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Affiliation(s)
- Magdalena Uzar
- Department of Child and Adolescent Psychiatry, Karol Jonscher Clinical Hospital, Poznan University of Medical Sciences, Szpitalna St. 27/33, 60-572 Poznan, Poland;
| | - Monika Dmitrzak-Węglarz
- Department of Psychiatric Genetics, Medical Biology Center, Poznan University of Medical Sciences, Rokietnicka St. 8, 60-806 Poznan, Poland;
| | - Agnieszka Słopień
- Department of Child and Adolescent Psychiatry, Karol Jonscher Clinical Hospital, Poznan University of Medical Sciences, Szpitalna St. 27/33, 60-572 Poznan, Poland;
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Pappa S, Caldwell-Dunn E, Kalniunas A, Kamal M. Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series. Front Psychiatry 2024; 15:1421698. [PMID: 39132320 PMCID: PMC11310661 DOI: 10.3389/fpsyt.2024.1421698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/17/2024] [Indexed: 08/13/2024] Open
Abstract
Background Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. Objectives To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Methods Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Results Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. Conclusion This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.
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Affiliation(s)
- Sofia Pappa
- Department of Psychiatry, West London National Health Service (NHS) Trust, London, United Kingdom
- Department of Brain Sciences, Imperial College London, London, United Kingdom
| | - Ellice Caldwell-Dunn
- Department of Psychiatry, West London National Health Service (NHS) Trust, London, United Kingdom
| | - Arturas Kalniunas
- Department of Psychiatry, West London National Health Service (NHS) Trust, London, United Kingdom
| | - Manzar Kamal
- Department of Psychiatry, West London National Health Service (NHS) Trust, London, United Kingdom
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Tomasetti C, Autullo G, Ballerini A, de Bartolomeis A, Dell'Osso B, Fiorentini A, Tonioni F, Villari V, De Berardis D. Treating depression in patients with borderline personality disorder: clinical clues on the use of antidepressants. Ann Gen Psychiatry 2024; 23:21. [PMID: 38816843 PMCID: PMC11140967 DOI: 10.1186/s12991-024-00507-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 05/23/2024] [Indexed: 06/01/2024] Open
Abstract
Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD.
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Affiliation(s)
- Carmine Tomasetti
- Department of Mental Health, Alzheimer Center of Giulianova, Hospital "Maria SS dello Splendore", ASL Teramo, Giulianova (TE), Italy.
| | - G Autullo
- Psychiatry and Psychology Institute, Catholic University of Sacred Heart of Rome, Rome, Italy
| | - A Ballerini
- Psychiatry Unit, Department of Health Science, University of Florence, Largo Brambilla 3, Florence, 50134, Italy
| | - A de Bartolomeis
- Laboratory of Molecular and Translational Psychiatry and Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Dentistry, University of Naples "Federico II", Naples, Italy
| | - B Dell'Osso
- Department of Mental Health, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy
| | - A Fiorentini
- Department of Neurosciences and Mental Health, Ca' Granda Ospedale Maggiore Policlinico, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), University of Milan, Milan, Italy
| | - F Tonioni
- Psychiatric Emergency Service, Department of Neuroscience and Mental Health, A.O.U. "Città della Salute e della Scienza", Turin, Italy
| | - V Villari
- Psychiatry and Psychology Institute, Catholic University of Sacred Heart of Rome, Rome, Italy
| | - D De Berardis
- Department of Mental Health, Mental Health Center of Giulianova, ASL Teramo, Teramo, Italy
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Francis B, Ganasan VA, Sulaiman ARB. Brexpiprazole Attenuates Aggression, Suicidality and Substance Use in Borderline Personality Disorder: A Case Series. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:283. [PMID: 38399570 PMCID: PMC10890360 DOI: 10.3390/medicina60020283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/30/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024]
Abstract
Background: Borderline personality disorder (BPD) is a heterogeneous and highly comorbid disorder. Suicidality, aggression and substance abuse are common presentations of BPD. Our case series is the first to highlight the role of brexpiprazole in improving these symptoms in patients with BPD. Case presentation: We describe three cases demonstrating the role of brexpiprazole in improving BPD's prominent features and comorbidities. All cases improved when brexpiprazole was added to their treatment regime. Case 1: A 26-year-old woman who was diagnosed with BPD and cyclothymia, presented to the psychiatric emergency unit with impulsive suicidal behaviour. Case 2: A 43-year-old woman suffering from BPD sought help due to her violent behaviour and emotional dysregulation. Case 3: A 22-year-old woman with underlying attention deficit and hyperactivity disorder, polysubstance use disorder and BPD presented with dysregulated emotions. Conclusions: Our case series provides anecdotal evidence of the potential role of brexpiprazole in attenuating suicidality, aggression and substance abuse in patients with BPD. We postulate that brexpiprazole's high affinity for the 5HT1A/5HT2A receptors, coupled with its low intrinsic effect on the D2/D3 receptor system, is fundamental in its actions to stabilise the aberrant dopaminergic and serotonergic signalling in BPD. Future research should focus on well-designed clinical trials investigating the efficacy of brexpiprazole in patients with BPD.
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Affiliation(s)
- Benedict Francis
- Department of Psychiatry, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Vijay A/L Ganasan
- Department of Psychiatry and Mental Health, Hospital Tuanku Ja’afar, Seremban 70300, Malaysia;
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Herzog P, Kube T, Fassbinder E. How childhood maltreatment alters perception and cognition - the predictive processing account of borderline personality disorder. Psychol Med 2022; 52:2899-2916. [PMID: 35979924 PMCID: PMC9693729 DOI: 10.1017/s0033291722002458] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/24/2022] [Accepted: 07/18/2022] [Indexed: 01/05/2023]
Abstract
Borderline personality disorder (BPD) is a severe mental disorder, comprised of heterogeneous psychological and neurobiological pathologies. Here, we propose a predictive processing (PP) account of BPD to integrate these seemingly unrelated pathologies. In particular, we argue that the experience of childhood maltreatment, which is highly prevalent in BPD, leaves a developmental legacy with two facets: first, a coarse-grained, alexithymic model of self and others - leading to a rigidity and inflexibility concerning beliefs about self and others. Second, this developmental legacy leads to a loss of confidence or precision afforded beliefs about the consequences of social behavior. This results in an over reliance on sensory evidence and social feedback, with concomitant lability, impulsivity and hypersensitivity. In terms of PP, people with BPD show a distorted belief updating in response to new information with two opposing manifestations: rapid changes in beliefs and a lack of belief updating despite disconfirmatory evidence. This account of distorted information processing has the potential to explain both the instability (of affect, self-image, and interpersonal relationships) and the rigidity (of beliefs about self and others) which is typical of BPD. At the neurobiological level, we propose that enhanced levels of dopamine are associated with the increased integration of negative social feedback, and we also discuss the hypothesis of an impaired inhibitory control of the prefrontal cortex in the processing of negative social information. Our account may provide a new understanding not only of the clinical aspects of BPD, but also a unifying theory of the corresponding neurobiological pathologies. We conclude by outlining some directions for future research on the behavioral, neurobiological, and computational underpinnings of this model, and point to some clinical implications of it.
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Affiliation(s)
- Philipp Herzog
- Department of Psychiatry and Psychotherapy, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany
- Department of Psychiatry and Psychotherapy, Christian-Albrechts-University of Kiel, Niemannsweg 147, D-24105 Kiel, Germany
- Department of Psychology, University of Koblenz-Landau, Ostbahnstr. 10, 76829 Landau, Germany
| | - Tobias Kube
- Department of Psychology, University of Koblenz-Landau, Ostbahnstr. 10, 76829 Landau, Germany
| | - Eva Fassbinder
- Department of Psychiatry and Psychotherapy, Christian-Albrechts-University of Kiel, Niemannsweg 147, D-24105 Kiel, Germany
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Wang WL, Hung HY, Chung CH, Hsu JW, Huang KL, Chan YY, Chien WC, Chen MH. Risk of Personality disorders among childhood maltreatment victims: A nation-wide population-based study in Taiwan. J Affect Disord 2022; 305:28-36. [PMID: 34965397 DOI: 10.1016/j.jad.2021.12.109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 12/21/2021] [Accepted: 12/24/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND To date, numerous cohort studies and meta-analyses have shown that childhood maltreatment is associated with a wide range of adverse physiological and psychological symptoms. Although childhood maltreatment has been linked to an increased risk of personality disorders, the direction and magnitude of the association remain uncertain. Therefore, this cohort study aimed to evaluate whether children who have suffered childhood maltreatment have a higher incidence of subsequent personality disorders, using a nationwide database in Taiwan. METHODS We conducted a large retrospective cohort study using data drawn from Taiwan's National Health Insurance Research Database between 2000 and 2015. A total of 10,345 children who experienced childhood maltreatment were identified using International Classification of Disease codes. They were then compared with 41,380 children who never experienced childhood maltreatment in terms of the prevalence rates of personality disorders. RESULTS Childhood maltreatment was associated with an increased risk of personality disorders (considering the control as reference: adjusted hazard ratio, 2.12; 95% confidence interval, 1.90-2.36; p < 0.001). The Kaplan-Meier analysis revealed a significantly higher 15-year cumulative incidence of personality disorders among childhood maltreatment victims than among controls (log-rank test, p < 0.001). CONCLUSIONS The present population-based study showed a positive association between prior childhood maltreatment and subsequent personality disorders in the general Taiwanese population. In order to reduce the risk of personality disorders, interventions should be implemented, identifying and supporting economically disadvantaged families and vulnerable children as early as possible.
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Affiliation(s)
- Wei-Li Wang
- Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Section 2, Taipei 11217, Taiwan; Master of Public Health Degree Program, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Hao-Yuan Hung
- Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 325, Chung-Gung Rd, Sec 2, Nei-Hu District 114, Taipei, Taiwan; School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Ju-Wei Hsu
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Section 2, Taipei 11217, Taiwan; Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kai-Lin Huang
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Section 2, Taipei 11217, Taiwan; Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yuan-Yu Chan
- Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Department of Psychology, Chung Yuan Christian University, Taoyuan, Taiwan
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 325, Chung-Gung Rd, Sec 2, Nei-Hu District 114, Taipei, Taiwan; School of Public Health, National Defense Medical Center, Taipei, Taiwan; National Defense Medical Center, Graduate Institute of Life Sciences, Taipei, Taiwan.
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Section 2, Taipei 11217, Taiwan; Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Trigo S, Silva PA, Cardoso GC, Soares MC. A test of context and sex-dependent dopaminergic effects on the behavior of a gregarious bird, the common waxbill Estrilda astrild. J Exp Biol 2022; 225:274524. [PMID: 35202471 DOI: 10.1242/jeb.243861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/14/2022] [Indexed: 11/20/2022]
Abstract
The Dopaminergic (DAergic) system has well known influences on behavioral and cognitive functions. Previous work with common waxbills (Estrilda astrild) reported context-specific DAergic effects that could have been due to social environment. Manipulating the dopamine D2-like receptor family (D2R) pathways had opposed effects on behavior depending on whether waxbills were tested alone or in a small cage with a mirror as social stimulus. Since waxbills are highly gregarious, it was hypothesized that being alone or perceiving to have a companion might explain this context-dependence. To test context-dependent DAergic effects, we compared behavioral effects of D2R manipulation in waxbills in the same familiar environment, but either alone or with a familiar, same-sex companion. We found that D2R agonism decreased movement and feeding, similarly to previous results when testing waxbills alone. However, contrary to the hypothesis of dependence on social context, we found that the behavioral effects of the D2R agonist were unchanged when waxbills were tested with a companion. The context-dependence reported earlier might thus be due to other factors, such as the stress of being in a novel environment (small cage) or with an unfamiliar social stimulus (mirror image). In tests with a companion, we also found a sex-specific social effect of D2R manipulation: D2R blocking tended to decrease aggression in males but to increase in females. Together with past work, our results suggest that DAergic effects on behavior involve different types of context- or sex-dependence.
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Affiliation(s)
- Sandra Trigo
- CIBIO/InBIO-Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal
| | - Paulo A Silva
- CIBIO/InBIO-Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal
| | - Gonçalo C Cardoso
- CIBIO/InBIO-Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal
| | - Marta C Soares
- CIBIO/InBIO-Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal
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10
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Schaub AC, Kirschner M, Schweinfurth N, Mählmann L, Kettelhack C, Engeli EE, Doll JPK, Borgwardt S, Lang UE, Kaiser S, Walter M, Herdener M, Wrege J, Schmidt A. Neural mapping of anhedonia across psychiatric diagnoses: A transdiagnostic neuroimaging analysis. Neuroimage Clin 2022; 32:102825. [PMID: 34544030 PMCID: PMC8455863 DOI: 10.1016/j.nicl.2021.102825] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/16/2021] [Accepted: 09/08/2021] [Indexed: 01/12/2023]
Abstract
Anhedonia is present in many different psychiatric disorders. Anhedonia has been associated with abnormal reward-related striatal dopamine functioning. This study tested whether transdiagnostic anhedonia expression mapped onto striatal volume. Our findings suggest volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities. Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses. T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume. ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses. Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.
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Affiliation(s)
| | - Matthias Kirschner
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
| | - Nina Schweinfurth
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Laura Mählmann
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Cedric Kettelhack
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Etna E Engeli
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
| | - Jessica P K Doll
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Stefan Borgwardt
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland; Department of Psychiatry and Psychotherapy, University of Lübeck, Germany
| | - Undine E Lang
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Stefan Kaiser
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Switzerland
| | - Marc Walter
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - Marcus Herdener
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
| | - Johannes Wrege
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland
| | - André Schmidt
- University of Basel, Department of Psychiatry (UPK), Basel, Switzerland.
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Bajouco M, Mota D. Cariprazine on Psychosis: Beyond Schizophrenia - A Case Series. Neuropsychiatr Dis Treat 2022; 18:1351-1362. [PMID: 35818373 PMCID: PMC9270979 DOI: 10.2147/ndt.s355941] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 05/26/2022] [Indexed: 11/23/2022] Open
Abstract
Cariprazine is an atypical antipsychotic that has D2 and D3 partial agonism properties in addition to the usual 5-HT2A receptor antagonist action of second-generation antipsychotics. It has a distinctly higher affinity for D3 receptors, which is 10-fold higher than for D2 receptors. Cariprazine is also a 5-HT1A partial agonist, with a potential antidepressant effect. Cariprazine has been approved for treatment of both positive and negative symptoms of schizophrenia and for treatment of bipolar disorder. It could potentially be used in depression as an add-on treatment. There are few data reporting effectiveness of cariprazine in the broader spectrum of psychosis. In this paper, the authors report three cases where cariprazine was used in the treatment of psychotic conditions other than schizophrenia, namely a first episode psychosis, a case of delusional disorder, and a case of a patient with borderline personality disorder and psychotic symptoms. The authors suggest that cariprazine may be effective in the treatment of psychosis in a broader sense and should be considered a first-line treatment option.
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Affiliation(s)
- Miguel Bajouco
- Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal
| | - David Mota
- Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Evans CL, Sawyer KS, Levy SA, Conklin JP, McDonough E, Gansler DA. Factors in the neurodevelopment of negative urgency: Findings from a community-dwelling sample. Brain Neurosci Adv 2022; 6:23982128221079548. [PMID: 35237725 PMCID: PMC8882942 DOI: 10.1177/23982128221079548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/22/2022] [Indexed: 11/29/2022] Open
Abstract
This study investigated neuroanatomic, genetic, cognitive, sociodemographic and emotional underpinnings of the Negative Urgency subscale of the Urgency, Premeditation, Perseverance, Sensation-Seeking and Positive Urgency Impulsive Behavior Scale in a healthy developmental sample. The goal of the investigation is to contribute to the harmonisation of behavioural, brain and neurogenetic aspects of behavioural self-control. Three domains - (1) Demographic, developmental, psychiatric and cognitive ability; (2) Regional brain volumes (neurobiological); and (3) Genetic variability (single nucleotide polymorphisms) - were examined, and models with relevant predictor variables were selected. Least absolute shrinkage and selection operator and best subset regressions were used to identify sparse models predicting negative urgency scores, which revealed that variables related to emotional regulation and right cingulate volume, as well as single nucleotide polymorphisms in CADM2 and SLC6A4, were associated with negative urgency. Our results contribute to the construct and criterion validity of negative urgency and support the hypothesis that negative urgency is a result of a complex array of influences across domains whose integration furthers developmental psychopathology research.
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Affiliation(s)
- Casey L. Evans
- Department of Psychology, Suffolk
University, Boston, MA, USA
- Psychology Assessment Center,
Massachusetts General Hospital, Boston, MA, USA
| | - Kayle S. Sawyer
- Boston University, Boston, MA,
USA
- VA Boston Healthcare System, Boston,
MA, USA
- Massachusetts General Hospital, Boston,
MA, USA
- Sawyer Scientific, Boston, MA,
USA
| | - Sarah A. Levy
- Department of Psychology, Suffolk
University, Boston, MA, USA
| | | | - EmilyKate McDonough
- Department of Medical Education, Tufts
University, Boston, MA, USA
- Department of Microbiology, Harvard
Medical School, Boston, MA, USA
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Grant JE, Valle S, Chesivoir E, Ehsan D, Chamberlain SR. A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder. Br J Psychiatry 2021; 220:1-6. [PMID: 35049469 PMCID: PMC7612273 DOI: 10.1192/bjp.2021.159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals. AIMS To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms. METHOD Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models. RESULTS There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo. CONCLUSIONS Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.
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Affiliation(s)
- Jon E. Grant
- University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL USA
| | - Stephanie Valle
- University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL USA
| | - Eve Chesivoir
- University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL USA
| | - Dustin Ehsan
- University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL USA
| | - Samuel R. Chamberlain
- Department of Psychiatry, Faculty of Medicine, University of Southampton, USA; and Southern Health NHS Foundation Trust, Southampton, USA
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Nature and nurture? A review of the literature on childhood maltreatment and genetic factors in the pathogenesis of borderline personality disorder. J Psychiatr Res 2021; 137:131-146. [PMID: 33677217 DOI: 10.1016/j.jpsychires.2020.12.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 11/22/2020] [Accepted: 12/09/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Borderline Personality Disorder (BPD) is a psychiatric disorder associated with significant morbidity and mortality. However, the neurobiological alterations underlying the condition remain poorly understood. As a result, existing treatments remain inadequate. One of the main risk factors for the development of BPD is a history of childhood maltreatment. However, it is considered neither causative nor specific to the condition. Current theory is therefore increasingly moving toward a 'Gene x Environment' (GxE) model of the condition. The purpose of the current work was to conduct a systematic literature review, which comprehensively identifies all published molecular level GxE studies that have explored the role of specific genetic loci, in influencing the risk of BPD following exposure to childhood abuse or neglect. METHODS Four electronic databases were used to systematically search for molecular level GxE studies of any design, which focused on the development of BPD following exposure to childhood abuse or neglect, without language or date restrictions. Articles were screened independently by two reviewers and results were synthesized narratively. RESULTS A total of 473 articles were screened of which sixteen were selected for inclusion in our review. Implicated genes were categorised according to their influence on; Neurotransmitter Systems, Neurodevelopment and Neuroendocrine Systems. CONCLUSIONS The identified studies have produced several relevant and statistically significant results. Of particular note, is the repeated finding that genes involved in HPA axis regulation, may be altered by exposure to childhood maltreatment, influencing subsequent susceptibility to BPD. This is both biologically plausible and of potential clinical significance.
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15
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Chen F, Lin X, Pan Y, Zeng X, Zhang S, Hu H, Yu M, Wu J. Insomnia partially mediates the relationship between pathological personality traits and depression: a case-control study. PeerJ 2021; 9:e11061. [PMID: 33850653 PMCID: PMC8018246 DOI: 10.7717/peerj.11061] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 02/13/2021] [Indexed: 12/28/2022] Open
Abstract
Background and Objective Personality disorders are frequently associated with insomnia and depression, but little is known about the inter-relationships among these variables. Therefore, this study examined these inter-relationships and the possible mediating effect of insomnia on the association between specific personality pathologies and depression severity. Methods There were 138 study participants, including 69 individuals with depression and 69 healthy controls. The main variables were measured by the Hamilton Depression Rating Scale-24 (HAMD-24), Athens Sleep Insomnia Scale (AIS), and the Personality Diagnostic Questionnaire (PDQ-4+). Multivariate linear regression and mediation analysis were conducted. Results With the exception of the antisocial personality score, all the PDQ-4+ scores and AIS scores were significantly higher in the depression group than in the healthy control group (p < 0.001). In the total sample, all personality pathology scores (p < 0.001), except the antisocial personality score, had significant positive correlations with the AIS scores and HAMD-24 scores, and the AIS scores and HAMD-24 scores were positively correlated (r = 0.620, p < 0.001). Regression analysis revealed that borderline personality, passive-aggressive personality, and insomnia positively predicted the severity of depression, after adjusting for sociodemographic covariates, and that insomnia partially mediated the associations of borderline personality and passive-aggressive personality with depression severity. Conclusions Borderline personality, passive-aggressive personality, and insomnia tend to increase the severity of depression, and the effect of borderline and passive-aggressive personality on depression severity may be partially mediated by insomnia. This is the first study to report these findings in a Chinese sample, and they may help researchers to understand the pathways from specific personality pathologies to the psychopathology of depression better, which should be useful for designing interventions to relieve depression severity, as the impact of specific personality pathology and insomnia should be considered.
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Affiliation(s)
- Fenglan Chen
- Department of Psychology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Xiujin Lin
- Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yuli Pan
- Department of Psychology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Xuan Zeng
- Department of Child Healthcare, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, China
| | - Shengjie Zhang
- Department of Psychology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Hong Hu
- Department of Psychology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Miaoyu Yu
- Department of Mental Health, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Junduan Wu
- Department of Psychology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
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16
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Grant JE, Chamberlain SR. Cariprazine treatment of borderline personality disorder: A case report. Psychiatry Clin Neurosci 2020; 74:511-512. [PMID: 32588527 DOI: 10.1111/pcn.13094] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 06/15/2020] [Accepted: 06/21/2020] [Indexed: 12/01/2022]
Affiliation(s)
- Jon E Grant
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Pritzker School of Medicine, Chicago, USA
| | - Samuel R Chamberlain
- Department of Psychiatry, University of Cambridge, Cambridge, UK.,Peterborough NHS Foundation Trust, Cambridge, UK
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17
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Mehren A, Reichert M, Coghill D, Müller HHO, Braun N, Philipsen A. Physical exercise in attention deficit hyperactivity disorder - evidence and implications for the treatment of borderline personality disorder. Borderline Personal Disord Emot Dysregul 2020; 7:1. [PMID: 31921425 PMCID: PMC6945516 DOI: 10.1186/s40479-019-0115-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 10/23/2019] [Indexed: 12/13/2022] Open
Abstract
A growing body of literature indicates a potential role for physical exercise in the treatment of attention deficit hyperactivity disorder (ADHD). Suggested effects include the reduction of ADHD core symptoms as well as improvements in executive functions. In the current review, we provide a short overview on the neurophysiological mechanisms assumed to underlie the beneficial effects of exercise. Further, we review the current evidence from experimental studies regarding both acute exercise and long-term interventions in ADHD. While the positive effects observed after acute aerobic exercise are promising, very few well-designed long-term intervention studies have been conducted yet. Moreover, although exercise effects have not yet been studied in borderline personality disorder (BPD), in the end of this paper we derive hypotheses why exercise could also be beneficial for this patient population.
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Affiliation(s)
- Aylin Mehren
- 1Department of Psychology, Biological Psychology Lab, European Medical School, University of Oldenburg, Oldenburg, Germany
| | - Markus Reichert
- 2Department of Applied Psychology, Mental mHealth Lab, Institute of Sports and Sports Science, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.,3Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - David Coghill
- 4Royal Children's Hospital, Melbourne, Victoria Australia
| | - Helge H O Müller
- 5Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
| | - Niclas Braun
- 5Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
| | - Alexandra Philipsen
- 5Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
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18
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Efficacy of intervention at traffic schools reducing impulsive action, and association with candidate gene variants. Acta Neuropsychiatr 2019; 31:159-166. [PMID: 31182183 DOI: 10.1017/neu.2019.2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Road traffic injuries are the leading cause of death among young people. Recognition of the contribution of impulsive behaviour may help novice drivers to behave more safely. Previously a brief intervention focusing on impulsive traffic behaviour conducted by psychologists in driving schools had been effective. The aim of this study was an independent re-evaluation of the effect of the intervention, as conducted by driving school teachers, and assessment of the potential associations with candidate genotypes. METHODS Driving school students (mean age 22.5, SD=7.9) were divided into intervention (n=704) and control (n=737) groups. Driving school teachers were trained to administer the intervention which consisted of a lecture and group work (1.5 h in total) on impulsivity. Traffic offences and crashes were monitored during 3 years, using police and traffic insurance fund databases. Functional polymorphisms of the dopamine transporter (DAT) and serotonin transporter genes (DAT1 VNTR and 5-HTTLPR) were assessed. RESULTS The intervention significantly lowered general traffic risk and prevalence of traffic accidents. DAT1 VNTR 9R carriers, particularly males, had higher general traffic risk in the whole sample. Female 5-HTTLPR s' allele carriers of the intervention group had the lowest general traffic risk. Intervention was most effective in female DAT1 VNTR 10R/10R homozygotes. CONCLUSIONS Brief impulsivity-centred intervention appears as a promising strategy for preventing risk-taking behaviour in novice drivers and can be fully integrated to driving school curriculum.
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19
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Relapse of drunk driving and association with traffic accidents, alcohol-related problems and biomarkers of impulsivity. Acta Neuropsychiatr 2019; 31:84-92. [PMID: 30472966 DOI: 10.1017/neu.2018.30] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Individual biological predispositions should play a role in risky driving behaviour. Platelet monoamine oxidase (MAO) activity, dopamine transporter gene (DAT1) and neuropeptide S receptor 1 (NPSR1) gene polymorphisms have been identified as markers of impulsivity, alcohol use and excessive risk-taking. We aimed to find out how this knowledge on neurobiology of impulsivity applies to drunk driving and traffic behaviour in general. METHODS We have longitudinally examined the behaviour of drunk drivers (n = 203) and controls (n = 211) in traffic, in association with their alcohol-related problems, personality measures and the three biomarkers. We analysed differences between the subjects based on whether they had committed driving while impaired by alcohol (DWI) violation in a 10-year time period after recruitment or not and investigated further, what kind of predictive value do the different biomarkers have in committing DWI and other traffic violations and accidents. RESULTS The original drunk drivers group had lower platelet MAO activity but further DWI was not significantly associated with this measure. Being a NPSR1 T-allele carrier contributed to the risk of repeatedly committing DWI. DAT1 9R carriers in contrast were involved in more traffic accidents by their own fault (active accidents), compared to 10R homozygotes in the whole sample. All groups with DWI also had significantly more alcohol-related problems and higher scores in maladaptive impulsivity compared to controls without DWI. CONCLUSIONS Established biological markers of alcohol use and impulsivity can be reliably associated with everyday traffic behaviour and help in contributing to the understanding of the need for more personalized prevention activities.
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20
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Stanley B, Perez-Rodriguez MM, Labouliere C, Roose S. A Neuroscience-Oriented Research Approach to Borderline Personality Disorder. J Pers Disord 2018; 32:784-822. [PMID: 29469663 DOI: 10.1521/pedi_2017_31_326] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Traditionally, the study of personality disorders had been based on psychoanalytic or behavioral models. Over the past two decades, there has been an emerging neuroscience model of borderline personality disorder (BPD) grounded in the concept of BPD as a condition in which dysfunctional neural circuits underlie its pathological dimensions, some of which include emotion dysregulation (broadly encompassing affective instability, negative affectivity, and hyperarousal), abnormal interpersonal functioning, and impulsive aggression. This article, initiated at a joint Columbia University- Cornell University Think Tank on BPD with representation from the Icahn School of Medicine at Mount Sinai, suggests how to advance research in BPD by studying the dimensions that underlie BPD in addition to studying the disorder as a unitary diagnostic entity. We suggest that linking the underlying neurobiological abnormalities to behavioral symptoms of the disorder can inform a research agenda to better understand BPD with its multiple presentations.
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Affiliation(s)
- Barbara Stanley
- Department of Psychiatry, Columbia University, New York City
| | | | | | - Steven Roose
- Department of Psychiatry, Columbia University, New York City.,New York State Psychiatric Institute, New York City
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21
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The effect of methylphenidate on decision making in patients with borderline personality disorder and attention-deficit/hyperactivity disorder. Int Clin Psychopharmacol 2018; 33:233-237. [PMID: 29847836 DOI: 10.1097/yic.0000000000000219] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Impaired decision making in patients with borderline personality disorder (BPD) has been reported in several studies. Although methylphenidate (MPH) is known to ameliorate impaired decision making in patients with attention-deficit/hyperactivity disorder (ADHD), it has not yet been examined in patients with BPD. We therefore assessed the efficacy of a single dose of MPH on cognitive functions and decision making in patients with BPD. Twenty-two patients diagnosed with BPD participated in the study. The study was a randomized, double-blind placebo-controlled, random block order cross-over trial. Patients participated in two sessions and performed the Test of Variables of Attention, a digit-span test, and the computerized Iowa Gambling Task, after they had been administered either the MPH or a placebo. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale-18. Lower scores on the inattention symptoms scale were associated with a greater improvement in decision making following the administration of MPH when compared with improvements in patients with higher ADHD scores [F(1,17)=5.63, P=0.030]. We conclude that MPH may improve decision making in patients with BPD, although this effect is mediated by the level of ADHD symptoms. Further studies are needed to assess whether a prolonged beneficial effect of MPH on decision making in patients with BPD might also be present in 'real life'.
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22
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Giourou E, Skokou M, Andrew SP, Alexopoulou K, Gourzis P, Jelastopulu E. Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma? World J Psychiatry 2018; 8:12-19. [PMID: 29568727 PMCID: PMC5862650 DOI: 10.5498/wjp.v8.i1.12] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 12/29/2017] [Accepted: 02/05/2018] [Indexed: 02/05/2023] Open
Abstract
Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities’ biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.
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Affiliation(s)
- Evangelia Giourou
- Department of Psychiatry, School of Medicine, University of Patras, Rio Patras 26500, Greece
- Department of Public Health, School of Medicine, University of Patras, Rio Patras 26500, Greece
| | - Maria Skokou
- Department of Psychiatry, School of Medicine, University of Patras, Rio Patras 26500, Greece
| | - Stuart P Andrew
- Specialist Care Team Limited, Lancashire LA4 4AY, United Kingdom
| | | | - Philippos Gourzis
- Department of Psychiatry, School of Medicine, University of Patras, Rio Patras 26500, Greece
| | - Eleni Jelastopulu
- Department of Public Health, School of Medicine, University of Patras, Rio Patras 26500, Greece
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Raghanti MA, Edler MK, Stephenson AR, Munger EL, Jacobs B, Hof PR, Sherwood CC, Holloway RL, Lovejoy CO. A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 2018; 115:E1108-E1116. [PMID: 29358369 PMCID: PMC5819450 DOI: 10.1073/pnas.1719666115] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
It has always been difficult to account for the evolution of certain human characters such as language, empathy, and altruism via individual reproductive success. However, the striatum, a subcortical region originally thought to be exclusively motor, is now known to contribute to social behaviors and "personality styles" that may link such complexities with natural selection. We here report that the human striatum exhibits a unique neurochemical profile that differs dramatically from those of other primates. The human signature of elevated striatal dopamine, serotonin, and neuropeptide Y, coupled with lowered acetylcholine, systematically favors externally driven behavior and greatly amplifies sensitivity to social cues that promote social conformity, empathy, and altruism. We propose that selection induced an initial form of this profile in early hominids, which increased their affiliative behavior, and that this shift either preceded or accompanied the adoption of bipedality and elimination of the sectorial canine. We further hypothesize that these changes were critical for increased individual fitness and promoted the adoption of social monogamy, which progressively increased cooperation as well as a dependence on tradition-based cultural transmission. These eventually facilitated the acquisition of language by elevating the reproductive advantage afforded those most sensitive to social cues.
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Affiliation(s)
- Mary Ann Raghanti
- Department of Anthropology, Kent State University, Kent, OH 44242;
- School of Biomedical Sciences, Kent State University, Kent, OH 44242
| | - Melissa K Edler
- Department of Anthropology, Kent State University, Kent, OH 44242
- School of Biomedical Sciences, Kent State University, Kent, OH 44242
- Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272
| | - Alexa R Stephenson
- Department of Anthropology, Kent State University, Kent, OH 44242
- School of Biomedical Sciences, Kent State University, Kent, OH 44242
| | - Emily L Munger
- Department of Anthropology, Kent State University, Kent, OH 44242
- School of Biomedical Sciences, Kent State University, Kent, OH 44242
| | - Bob Jacobs
- Laboratory of Quantitative Neuromorphology, Department of Psychology, Colorado College, Colorado Springs, CO 80903
| | - Patrick R Hof
- Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029
- New York Consortium in Evolutionary Primatology, New York, NY 10024
| | - Chet C Sherwood
- Department of Anthropology, The George Washington University, Washington, DC 20052
- Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, DC 20052
| | - Ralph L Holloway
- Department of Anthropology, Columbia University, New York, NY 10027
| | - C Owen Lovejoy
- Department of Anthropology, Kent State University, Kent, OH 44242;
- School of Biomedical Sciences, Kent State University, Kent, OH 44242
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Ali AA, Ahmed HI, Barakat BM, Elariny HA. Impact of Sensory Contact Model on Psychosocial Stress and Correlation with Immunological Changes. JOURNAL OF EXPLORATORY RESEARCH IN PHARMACOLOGY 2018; 3:19-29. [DOI: 10.14218/jerp.2017.00017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Cattane N, Rossi R, Lanfredi M, Cattaneo A. Borderline personality disorder and childhood trauma: exploring the affected biological systems and mechanisms. BMC Psychiatry 2017; 17:221. [PMID: 28619017 PMCID: PMC5472954 DOI: 10.1186/s12888-017-1383-2] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 06/06/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND 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. DISCUSSION 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.
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Affiliation(s)
- Nadia Cattane
- grid.419422.8Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, via Pilastroni 4, Brescia, Italy
| | - Roberta Rossi
- grid.419422.8Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, via Pilastroni 4, Brescia, Italy
| | - Mariangela Lanfredi
- grid.419422.8Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, via Pilastroni 4, Brescia, Italy
| | - Annamaria Cattaneo
- Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, via Pilastroni 4, Brescia, Italy. .,Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK. .,Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK.
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Core, social and moral disgust are bounded: A review on behavioral and neural bases of repugnance in clinical disorders. Neurosci Biobehav Rev 2017; 80:185-200. [PMID: 28506923 DOI: 10.1016/j.neubiorev.2017.05.008] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 04/19/2017] [Accepted: 05/09/2017] [Indexed: 12/12/2022]
Abstract
Disgust is a multifaceted experience that might affect several aspects of life. Here, we reviewed research on neurological and psychiatric disorders that are characterized by abnormal disgust processing to test the hypothesis of a shared neurocognitive architecture in the representation of three disgust domains: i) personal experience of 'core disgust'; ii) social disgust, i.e., sensitivity to others' expressions of disgust; iii) moral disgust, i.e., sensitivity to ethical violations. Our review provides some support to the shared neurocognitive hypothesis and suggests that the insula might be the "hub" structure linking the three domains of disgust sensitivity, while other brain regions may subserve specific facets of the multidimensional experience. Our review also suggests a role of serotonin core and moral disgust, supporting "neo-sentimentalist" theories of morality, which posit a causal role of affect in moral judgment.
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Mortlock AM, Larkin F, Ross CC, Gupta N, Sengupta S, Das M. Effectiveness of paliperidone depot injection in seriously violent men with comorbid schizophrenia and dissocial personality disorder in a UK high-security hospital. Ther Adv Psychopharmacol 2017; 7:169-179. [PMID: 28540038 PMCID: PMC5431400 DOI: 10.1177/2045125317693513] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 05/05/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND High-security hospital patients are often complex in presentation and are characterized by treatment resistance, medication nonadherence and history of violence. Paliperidone is licensed both as an oral and depot antipsychotic medication in the treatment of schizophrenia. Clinical trials have shown that paliperidone depot is well tolerated with similar efficacy to risperidone depot but with additional practical advantages. Whilst data exist for the effectiveness of paliperidone palmitate (PP), there are no studies involving patients in forensic settings or those with comorbid personality disorder. Our aim was to evaluate the effectiveness of PP on violence, aggression and personality disorder symptoms. METHODS This project was a retrospective service evaluation involving 11 patients, carried out in a high-security hospital. A combination of patient records and interviews with the treating consultant psychiatrist were used to ascertain a Clinical Global Impression (CGI) score, the effect of PP on specific personality disorder symptom domains (cognitive-perceptual, impulsive-behavioural dyscontrol and affective dysregulation) and incidents of violence and aggression. Engagement with occupational and psychological therapies was also evaluated. Metabolic parameters were reviewed. RESULTS A total of 6 out of 11 patients continued on PP, most of whom had schizophrenia and dissocial personality disorder with histories of violence. All showed improvement in the CGI score with associated benefits in the three personality symptom domains. Overall, two patients demonstrated a reduction in the risk of violence. There was improvement in engagement with occupational therapy and psychological work. No significant effects on metabolic parameters were noted although hyperprolactinaemia, albeit asymptomatic, was consistently recorded. CONCLUSIONS This pragmatic service evaluation of a small but complex patient group demonstrated, for the first time, that PP was effective in reducing violence as well as improving personality pathology across all dimensions: a finding which could have significant implications for management of such high-security patients.
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Affiliation(s)
- Anna-Marie Mortlock
- Specialist Registrar Forensic Psychiatry, Broadmoor Hospital, West London Mental Health Trust, Crowthorne, UK
| | - Fintan Larkin
- Consultant Forensic Psychiatrist, Broadmoor Hospital, West London Mental Health Trust, Crowthorne, UK
| | - Callum C. Ross
- Consultant Forensic Psychiatrist, Broadmoor Hospital, West London Mental Health Trust, Crowthorne, UK
| | - Nitin Gupta
- Professor, Department of Psychiatry, Government Medical College, Chandigarh, India
| | - Samrat Sengupta
- Consultant Forensic Psychiatrist, Broadmoor Hospital, West London Mental Health Trust, Crowthorne, UK
| | - Mrigendra Das
- Consultant Forensic Psychiatrist, Top End Mental Health Service, PO Box 140, Parap, NT 0804, Australia
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Genetic and environmental influences on the codevelopment among borderline personality disorder traits, major depression symptoms, and substance use disorder symptoms from adolescence to young adulthood. Dev Psychopathol 2017; 30:49-65. [PMID: 28420454 DOI: 10.1017/s0954579417000463] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Although borderline personality disorder (BPD) traits decline from adolescence to adulthood, comorbid psychopathology such as symptoms of major depressive disorder (MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt this normative decline. Using a longitudinal sample of female twins (N = 1,763), we examined if levels of BPD traits were correlated with changes in MDD, AUD, and DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model examined the contributions of genetic and environmental factors to the relationships between developmental components of these phenotypes. Higher BPD trait levels predicted a greater rate of increase in AUD and DUD symptoms, and higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from ages 14 to 24. Common genetic influences accounted for the associations between BPD traits and each disorder, as well as the interrelationships of AUD and DUD symptoms. Both genetic and nonshared environmental influences accounted for the correlated levels between BPD traits and MDD symptoms, but solely environmental influences accounted for the correlated changes between the two over time. Results indicate that higher levels of BPD traits may contribute to an earlier onset and faster escalation of AUD and DUD symptoms, and substance use problems slow the normative decline in BPD traits. Overall, our data suggests that primarily genetic influences contribute to the comorbidity between BPD features and substance use disorder symptoms. We discuss our data in the context of two major theories of developmental psychopathology and comorbidity.
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Rotenberg VS. Sexual Disorders Caused by Antidepressants: Considerations in the Context of Brain Hemisphere Functions. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/bf03379566] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Abstract
All phases of normal sexual activity are under the control of the right hemisphere coupled with limbic structures, and depression is characterized by the functional insufficiency of this system. At the same time, those modern antidepressants that cause sexual disorders are activating the left hemisphere and determine its domination on the expense of the right one and disturb free and spontaneous emotional interrelationships, sexual behavior and pleasure. Those antidepressants that do not cause sexual dysfunction are not activating predominantly the left hemisphere structures and activate the limbic brain zones responsible for reward, reinforcement and emotional excitement.
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Andreou C, Kleinert J, Steinmann S, Fuger U, Leicht G, Mulert C. Oscillatory responses to reward processing in borderline personality disorder. World J Biol Psychiatry 2016. [PMID: 26212791 DOI: 10.3109/15622975.2015.1054880] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES Previous electrophysiological studies have confirmed impaired reward processing in patients with BPD. However, it is not clear which aspects of reward processing are affected and which brain regions are involved. The present study investigated both evoked and induced event-related oscillations (EROs) to feedback events (thought to represent different aspects of feedback processing), and used source localization (sLORETA) to assess activity in two areas known to contribute to reward processing, the dorsomedial prefrontal/anterior cingulate cortex (dmPFC/ACC) and the orbitofrontal cortex (OFC). METHODS Eighteen patients with BPD and 22 healthy controls performed a gambling task, while 64-channel electroencephalographic activity was recorded. Evoked and induced theta and high-beta band EROs as well as activity in the two regions of interest were investigated depending on the valence and magnitude of feedback events. RESULTS Theta-band responses to negative feedback were reduced in BPD, an effect that involved only evoked responses and the dmPFC/ ACC region, and was associated with trait impulsivity in patients. sLORETA analyses revealed disturbed evoked responses depending on feedback magnitude in the theta (OFC) and high-beta (dmPFC/ACC and OFC) frequency range. CONCLUSIONS The results indicate multiple dysfunctions of feedback processing in patients with BPD, implicating several distinct subsets of reward-processing mechanisms.
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Affiliation(s)
- Christina Andreou
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Julia Kleinert
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Saskia Steinmann
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Ulrike Fuger
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Gregor Leicht
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Christoph Mulert
- a Department of Psychiatry and Psychotherapy , University Medical Center Hamburg-Eppendorf , Hamburg , Germany
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Lee S, Yu JS, Lee S. A Pilot Study of Psychological Traits in the Sasang Constitution According to the Braverman Nature Assessment. J Pharmacopuncture 2016; 18:32-7. [PMID: 27547483 PMCID: PMC4984615 DOI: 10.3831/kpi.2015.18.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Objectives: The purpose of this study was to investigate the psychological characteristics of the Sasang constitutions by using Braverman nature assessment (BNA). Methods: One hundred seventy-four students participated in this study, and among them, the 142 individuals who had clearly identified Sasang constitutional types were used for the analysis. Sasang constitutions and the Braverman temperaments of the subjects were determined by using a questionnaire for the Sasang constitution classification (QSCC) II and BNA, respectively. Body mass index (BMI) was used to compare the inclinations of the Sasang constitutions and Braverman temperament types. Results: Significant differences in Braverman temperament type existed among the Sasang constitutions (P = 0.042), and the relations between Soyangin and the dopamine type and between Taeeumin and the gamma-aminobutyric acid (GABA) type were meaningful. Significant differences were also shown in the comparison with the Yin and the Yang constitutions (P = 0.017), and the post-hoc analysis showed a strong and significant relation between the Yang constitution and the dopamine type and between the Yin constitution and the GABA type. The one–way analysis of variance (ANOVA) and the independent t-test were conducted to examine the BMI and the degree of obesity among the Sasang constitutions and the Braverman temperament types. Concerning the BMI, Taeeumin showed a bigger BMI than the other constitutions (P < 0.001), but no significant differences in the BMI were observed between the Braverman temperament types. Conclusion: Soyangin has a close relationship to the dopamine type and Taeeumin has a close relationship to the GABA type. The correlation between two types were more clear when the Yin and the Yang types were compared to Braverman temperaments. These results may serve as a basis for identifying the psychological traits of Sasang constitutional types, especially in regard to the characteristics related to the four Braverman temperament types.
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Affiliation(s)
- Soojin Lee
- Department of Physiology, College of Korean Medicine, Sangji University, Wonju, Korea
| | - Jun-Sang Yu
- Department of Sasang Constitutional Medicine, College of Korean Medicine, Sangji University, Wonju, Korea
| | - Siwoo Lee
- Korea Institute of Oriental Medicine, Daejeon, Korea
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Herbort MC, Soch J, Wüstenberg T, Krauel K, Pujara M, Koenigs M, Gallinat J, Walter H, Roepke S, Schott BH. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder. NEUROIMAGE-CLINICAL 2016; 12:724-736. [PMID: 27766203 PMCID: PMC5067102 DOI: 10.1016/j.nicl.2016.08.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 11/18/2022]
Abstract
Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.
We investigated striatal reward and loss anticipation in patients with Borderline Personality Disorder (BPD) and controls BPD patients relative to controls exhibited reduced ventral striatal / nucleus accumbens (VS/NAcc) anticipation responses In healthy controls, VS responses to gains and losses correlated positively with impulsivity BPD patients exhibited a negative correlation between loss responses and impulsivity. Our results suggest that impulsivity in BPD patients may in part result from impaired anticipation of aversive outcomes.
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Affiliation(s)
- Maike C. Herbort
- Leibniz Institute for Neurobiology, Magdeburg, Germany
- Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Department of Psychology, Humboldt University, Berlin, Germany
| | - Joram Soch
- Leibniz Institute for Neurobiology, Magdeburg, Germany
- Bernstein Center for Computational Neuroscience, Humboldt University, Berlin, Germany
| | - Torsten Wüstenberg
- Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Kerstin Krauel
- Department of Child and Adolescent Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
| | - Maia Pujara
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
| | - Michael Koenigs
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
| | - Jürgen Gallinat
- Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Psychiatry and Psychotherapy, University Hospital Eppendorf, Hamburg, Germany
| | - Henrik Walter
- Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Stefan Roepke
- Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Björn H. Schott
- Leibniz Institute for Neurobiology, Magdeburg, Germany
- Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
- Corresponding author at: Leibniz-Institut für Neurobiologie, Brenneckestr. 6, 39118 Magdeburg, Germany.Leibniz-Institut für NeurobiologieBrenneckestr. 6Magdeburg39118Germany
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Congdon E, Canli T. The Endophenotype of Impulsivity: Reaching Consilience Through Behavioral, Genetic, and Neuroimaging Approaches. ACTA ACUST UNITED AC 2016; 4:262-81. [PMID: 16585800 DOI: 10.1177/1534582305285980] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Impulsivity is a multidimensional construct with implications for understanding the etiology and treatment of multiple forms of psychopathology. As a multidimensional construct, however, the processes underlying impulsivity, particularly behavioral inhibition, must be separated to allow for investigations into its neurogenetic bases. Evidence from both animal and human studies supports the role of dopamine in impulsivity, and neuroimaging research is elucidating brain regions involved in behavioral inhibition. Evidence is now emerging that suggests an interaction between dopamine system genes and frontal brain regions in underlying individual differences in behavioral inhibition. However, to reach a comprehensive understanding of the neurogenetic bases of behavioral inhibition, an appropriate framework is required. Therefore, it is proposed that by identifying intervening variables more sensitive to the effects of genetic variation, known as an endophenotype approach, we will be able to overcome many of the methodological limitations that prevent a better understanding at present.
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Affiliation(s)
- Eliza Congdon
- Department of Psychology, Stony Brook University, NY, USA
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Nicol K, Pope M, Romaniuk L, Hall J. Childhood trauma, midbrain activation and psychotic symptoms in borderline personality disorder. Transl Psychiatry 2015; 5:e559. [PMID: 25942040 PMCID: PMC4471284 DOI: 10.1038/tp.2015.53] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 02/25/2015] [Accepted: 03/09/2015] [Indexed: 01/18/2023] Open
Abstract
Childhood trauma is believed to contribute to the development of borderline personality disorder (BPD), however the mechanism by which childhood trauma increases risk for specific symptoms of the disorder is not well understood. Here, we explore the relationship between childhood trauma, brain activation in response to emotional stimuli and psychotic symptoms in BPD. Twenty individuals with a diagnosis of BPD and 16 healthy controls were recruited to undergo a functional MRI scan, during which they viewed images of faces expressing the emotion of fear. Participants also completed the childhood trauma questionnaire (CTQ) and a structured clinical interview. Between-group differences in brain activation to fearful faces were limited to decreased activation in the BPD group in the right cuneus. However, within the BPD group, there was a significant positive correlation between physical abuse scores on the CTQ and BOLD signal in the midbrain, pulvinar and medial frontal gyrus to fearful (versus neutral) faces. In addition there was a significant correlation between midbrain activation and reported psychotic symptoms in the BPD group (P<0.05). These results show that physical abuse in childhood is, in individuals with BPD, associated with significantly increased activation of a network of brain regions including the midbrain in response to emotional stimuli. Sustained differences in the response of the midbrain to emotional stimuli in individuals with BPD who suffered childhood physical abuse may underlie the vulnerability of these patients to developing psychotic symptoms.
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Affiliation(s)
- K Nicol
- Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK
| | - M Pope
- Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK
| | - L Romaniuk
- Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK
| | - J Hall
- Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK,Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK,MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK,Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK. E-mail:
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McHugh PC, Buckley DA. The Structure and Function of the Dopamine Transporter and its Role in CNS Diseases. HORMONES AND TRANSPORT SYSTEMS 2015; 98:339-69. [DOI: 10.1016/bs.vh.2014.12.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Mobascher A, Bohus M, Dahmen N, Dietl L, Giegling I, Jungkunz M, Kleindienst N, Limberger M, Meisenzahl E, Rietschel M, Roepke S, Schmahl C, Schott B, Schwarze CE, Tadić A, Treutlein J, Vogel F, Witt SH, Zetzsche T, Rujescu D, Lieb K. Association between dopa decarboxylase gene variants and borderline personality disorder. Psychiatry Res 2014; 219:693-5. [PMID: 25017620 DOI: 10.1016/j.psychres.2014.06.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 06/05/2014] [Accepted: 06/20/2014] [Indexed: 11/29/2022]
Abstract
Despite heritability estimates of 37-69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene.
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Affiliation(s)
- Arian Mobascher
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany.
| | - Martin Bohus
- Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Norbert Dahmen
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany
| | - Lydie Dietl
- Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany
| | - Ina Giegling
- Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany; Department of Psychiatry and Psychotherapy, Martin-Luther University Halle-Wittenberg, Germany
| | - Martin Jungkunz
- Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Nikolaus Kleindienst
- Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Matthias Limberger
- Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Eva Meisenzahl
- Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany
| | - Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Stefan Roepke
- Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany
| | - Christian Schmahl
- Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Björn Schott
- Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany; Leibniz Institute for Neurobiology, Magdeburg, Germany
| | - Cornelia E Schwarze
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany
| | - André Tadić
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany
| | - Jens Treutlein
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Friederike Vogel
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany
| | - Stephanie H Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Thomas Zetzsche
- Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany
| | - Dan Rujescu
- Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany; Department of Psychiatry and Psychotherapy, Martin-Luther University Halle-Wittenberg, Germany
| | - Klaus Lieb
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany
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Brown D, Larkin F, Sengupta S, Romero-Ureclay JL, Ross CC, Gupta N, Vinestock M, Das M. Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital. CNS Spectr 2014; 19:391-402. [PMID: 24698103 PMCID: PMC4255317 DOI: 10.1017/s1092852914000157] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 02/07/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVE A number of studies have demonstrated the anti-aggressive properties of clozapine in schizophrenia and its positive effect in borderline personality disorder. There is no published literature on the treatment of antisocial personality disorder (ASPD) with clozapine. We present a case series of 7 patients with primary ASPD and high psychopathic traits treated with clozapine, having a significant history of serious violence and currently detained in a UK based high-security hospital. METHODS A retrospective review of case notes was carried out to formulate Clinical Global Impression (CGI) scores and record incidents of violence and aggression. Effect on specific symptom domains (cognitive-perceptual, impulsive-behavioural dyscontrol, affective dysregulation) was also noted. Metabolic parameters and serum clozapine levels were also sampled. RESULTS All 7 patients showed significant improvement on clozapine. It was shown to benefit all symptom domains, especially impulsive behavioral dyscontrol and anger. The number of violent incidents committed by 6 of the 7 patients reduced significantly, and all patients' risk of violence reduced. Clozapine serum levels for 6 of the 7 patients were in the range 150-350 ng/mL. CONCLUSION Clozapine is of benefit in reducing the clinical severity of ASPD. It improved all symptom domains, especially impulsive-behavioral dyscontrol and anger, and reduced levels of aggression and violence, especially at lower doses (serum levels <350 ng/m). To our knowledge, this is the first account of clozapine treatment in patients with ASPD and high psychopathy.
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Affiliation(s)
- Darcy Brown
- The School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| | - Fintan Larkin
- Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
| | - Samrat Sengupta
- Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
| | | | - Callum C. Ross
- Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
| | - Nitin Gupta
- Department of Psychiatry, Government Medical College and Hospital, Chandigarh, India
| | - Morris Vinestock
- Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
| | - Mrigendra Das
- Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
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Martel MO, Jamison RN, Wasan AD, Edwards RR. The association between catastrophizing and craving in patients with chronic pain prescribed opioid therapy: a preliminary analysis. PAIN MEDICINE 2014; 15:1757-64. [PMID: 24612286 DOI: 10.1111/pme.12416] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND A growing number of studies have shown that opioid craving (i.e., the perceived need or desire to consume opioids) is one of the strongest determinants of prescription opioid misuse in patients with chronic pain prescribed opioid therapy. To date, however, the factors that are associated with craving in patients with pain remain largely unexplored. Based on previous research, there is reason to believe that catastrophizing might be associated with heightened opioid craving. OBJECTIVES To test the hypothesis that catastrophizing would be associated with heightened craving in patients with chronic pain prescribed long-term opioid therapy. DESIGN AND SUBJECTS, AND METHODS In this cross-sectional study, 109 patients with chronic pain were asked to provide self-reports of catastrophizing and craving. Patients also provided self-reports of pain intensity and depressive symptoms. RESULTS We found that higher levels of catastrophizing were associated with higher levels of craving. Importantly, results of a regression analysis revealed that the association between catastrophizing and craving remained significant even after controlling for a host of demographic (i.e., age, sex), psychological (i.e., depressive symptoms), medical (i.e., pain intensity, pain duration), and medication regimen (i.e., opioid doses) variables. CONCLUSIONS Our preliminary findings provide valuable new insights into the determinants of craving in patients with pain. The finding that catastrophizing was associated with craving even after controlling for a host of demographic, psychological, medical, and medication regimen variables is particularly striking, and raises questions concerning the factors that underlie the association between catastrophizing and craving in patients prescribed opioid therapy.
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Affiliation(s)
- Marc O Martel
- Department of Anesthesiology, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts, USA
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Amad A, Ramoz N, Thomas P, Jardri R, Gorwood P. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neurosci Biobehav Rev 2014; 40:6-19. [PMID: 24456942 DOI: 10.1016/j.neubiorev.2014.01.003] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Revised: 12/13/2013] [Accepted: 01/09/2014] [Indexed: 12/31/2022]
Abstract
Borderline personality disorder (BPD) is one of the most common mental disorders and is characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Here, we performed a systematic review of the literature concerning the genetics of BPD, including familial and twin studies, association studies, and gene-environment interaction studies. Moreover, meta-analyses were performed when at least two case-control studies testing the same polymorphism were available. For each gene variant, a pooled odds ratio (OR) was calculated using fixed or random effects models. Familial and twin studies largely support the potential role of a genetic vulnerability at the root of BPD, with an estimated heritability of approximately 40%. Moreover, there is evidence for both gene-environment interactions and correlations. However, association studies for BPD are sparse, making it difficult to draw clear conclusions. According to our meta-analysis, no significant associations were found for the serotonin transporter gene, the tryptophan hydroxylase 1 gene, or the serotonin 1B receptor gene. We hypothesize that such a discrepancy (negative association studies but high heritability of the disorder) could be understandable through a paradigm shift, in which "plasticity" genes (rather than "vulnerability" genes) would be involved. Such a framework postulates a balance between positive and negative events, which interact with plasticity genes in the genesis of BPD.
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Affiliation(s)
- Ali Amad
- Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France.
| | - Nicolas Ramoz
- INSERM U894, Centre de Psychiatrie & Neurosciences, Paris, France
| | - Pierre Thomas
- Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France
| | - Renaud Jardri
- Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France
| | - Philip Gorwood
- INSERM U894, Centre de Psychiatrie & Neurosciences, Paris, France; Sainte-Anne Hospital (Paris-Descartes University), Paris, France
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Joyce PR, Stephenson J, Kennedy M, Mulder RT, McHugh PC. The presence of both serotonin 1A receptor (HTR1A) and dopamine transporter (DAT1) gene variants increase the risk of borderline personality disorder. Front Genet 2014; 4:313. [PMID: 24432029 PMCID: PMC3882668 DOI: 10.3389/fgene.2013.00313] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 12/22/2013] [Indexed: 12/31/2022] Open
Abstract
Dysfunction in the dopaminergic and serotonergic neurotransmitter systems has been demonstrated to be important in the etiology of borderline personality disorder (BPD). We investigated the relationship of two BPD risk factors, the HTR1A promoter polymorphism -1019C > G (rs6295) and the dopamine transporter (DAT1) repeat allele, with BPD in a major depressive disorder cohort of 367 patients. Out-patients with major depressive disorder were recruited for two treatment trials and assessed for personality disorders, including BPD. DNA samples were collected and the rs6295 polymorphism was detected with a TaqMan(®) assay. The DAT1 repeat allele was genotyped using a modified PCR method. The impact of polymorphisms on BPD was statistically analyzed using uncontrolled logistic and multiple logistic regression models. BPD patients had higher frequencies of the DAT1 9,9 (OR = 2.67) and 9,10 (OR = 3.67) genotypes and also those homozygous HTR1A G allele (OR = 2.03). No significant interactions between HTR1A and DAT1 genotypes, were observed; however, an increased risk of BPD was observed for those patients who were either 9,10; G,G (OR = 6.64) and 9,9; C,G (OR = 5.42). Furthermore, the odds of BPD in patients exhibiting high-risk variants of these two genes differed from those of patients in low-risk groups by up to a factor of 9. Our study provides evidence implicating the importance of the serotonergic and dopaminergic systems in BPD and that the interaction between genes from different neurotransmitters may play a role in the susceptibility to BPD.
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Affiliation(s)
- Peter R. Joyce
- Department of Psychological Medicine, University of OtagoChristchurch, New Zealand
| | - John Stephenson
- Department of Health Sciences, School of Human and Health Sciences, University of HuddersfieldHuddersfield, UK
| | - Martin Kennedy
- Department of Pathology, University of OtagoChristchurch, New Zealand
| | - Roger T. Mulder
- Department of Psychological Medicine, University of OtagoChristchurch, New Zealand
| | - Patrick C. McHugh
- Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of HuddersfieldHuddersfield, UK
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41
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MacGregor MW, Lamborn P. Personality Assessment Inventory profiles of university students with eating disorders. J Eat Disord 2014; 2:20. [PMID: 25426291 PMCID: PMC4243782 DOI: 10.1186/s40337-014-0020-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 07/08/2014] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Eating disorders are complex disorders that involve medical and psychological symptoms. Understanding the psychological factors associated with different eating disorders is important for assessment, diagnosis, and treatment. METHODS This study sought to determine on which of the 22 Personality Assessment Inventory (PAI) scales patients with anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified (EDNOS) differed, and whether the PAI can be used to classify eating disorder subtypes. Because we were interested in both whether the PAI could be used to differentiate eating disorder subtypes from each other, as well as from other disorders, we also included a group of patients with major depression. RESULTS The three eating disorder groups did differ significantly from each other, and from the patients with depression, on a number of the PAI scales. Only two PAI scales (Anxiety and Depression), however, exceeded a T-score of 70 for the patients with anorexia nervosa, no scales exceeded a T-score of 70 for the patients with bulimia nervosa or EDNOS, and only two exceeded a T-score of 70 for the patients with depression (Depression and Suicide). A discriminant function analysis revealed an overall correct classification between the groups of 81.6%. CONCLUSIONS The PAI helps to understand the psychological factors associated with eating disorders and can be used to assist with assessment. Continued investigation using the PAI in an eating disordered population is supported.
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Affiliation(s)
| | - Paige Lamborn
- University of Saskatchewan, Saskatoon, Saskatchewan Canada
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Negative reward expectations in Borderline Personality Disorder patients: neurophysiological evidence. Biol Psychol 2013; 94:388-96. [PMID: 23969232 DOI: 10.1016/j.biopsycho.2013.08.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Revised: 08/01/2013] [Accepted: 08/08/2013] [Indexed: 12/31/2022]
Abstract
Borderline Personality Disorder (BPD) patients present profound disturbances in affect regulation and impulse control which could reflect a dysfunction in reward-related processes. The current study investigated these processes in a sample of 18 BPD patients and 18 matched healthy controls, using an event-related brain potentials methodology. Results revealed a reduction in the amplitude of the Feedback-Related Negativity of BPD patients, which is a neurophysiological index of the impact of negative feedback in reward-related tasks. This reduction, in the effect of negative feedback in BPD patients, was accompanied by a different behavioral pattern of risk choice compared to healthy participants. These findings confirm a dysfunctional reward system in BDP patients, which might compromise their capacity to build positive expectations of future rewards and decision making.
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43
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Wildes JE, Marcus MD. Alternative methods of classifying eating disorders: models incorporating comorbid psychopathology and associated features. Clin Psychol Rev 2013; 33:383-94. [PMID: 23416343 DOI: 10.1016/j.cpr.2013.01.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 11/30/2012] [Accepted: 01/15/2013] [Indexed: 10/27/2022]
Abstract
There is increasing recognition of the limitations of current approaches to psychiatric classification. Nowhere is this more apparent than in the eating disorders (EDs). Several alternative methods of classifying EDs have been proposed, which can be divided into two major groups: 1) those that have classified individuals on the basis of disordered eating symptoms; and, 2) those that have classified individuals on the basis of comorbid psychopathology and associated features. Several reviews have addressed symptom-based approaches to ED classification, but we are aware of no paper that has critically examined comorbidity-based systems. Thus, in this paper, we review models of classifying EDs that incorporate information about comorbid psychopathology and associated features. Early approaches are described first, followed by more recent scholarly contributions to comorbidity-based ED classification. Importantly, several areas of overlap among the classification schemes are identified that may have implications for future research. In particular, we note similarities between early models and newer studies in the salience of impulsivity, compulsivity, distress, and inhibition versus risk taking. Finally, we close with directions for future work, with an emphasis on neurobiologically-informed research to elucidate basic behavioral and neuropsychological correlates of comorbidity-based ED classes, as well as implications for treatment.
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Affiliation(s)
- Jennifer E Wildes
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Doran N, Schweizer CA, Myers MG, Greenwood TA. A prospective study of the effects of the DRD2/ANKK1 TaqIA polymorphism and impulsivity on smoking initiation. Subst Use Misuse 2013; 48:106-16. [PMID: 23153044 DOI: 10.3109/10826084.2012.733791] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
This study tested whether DRD2/ANKK1 TaqIA genotype predicted smoking initiation and subsequent use, and effects were mediated by sensation seeking and negative urgency. Between 2009 and 2012, college never smokers (n = 387) completed six assessments over 15 months; those who reported smoking were classified as initiators. Logistic regression indicated that the A1 allele was associated with initiation (p = .003). This effect was partially mediated by sensation seeking and negative urgency. Effects were stronger in Asian Americans. Findings have implications for improving prevention by including elements focused on urges to seek positive or negative reinforcement. Limitations and future directions are discussed.
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Affiliation(s)
- Neal Doran
- Department of Psychiatry, University of California, San Diego, San Diego, California 92161, USA.
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45
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Antoniadis D, Samakouri M, Livaditis M. The association of bipolar spectrum disorders and borderline personality disorder. Psychiatr Q 2012; 83:449-65. [PMID: 22392448 DOI: 10.1007/s11126-012-9214-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Bipolar disorder (BD) and borderline personality disorder (BPD) are two different entities sharing a variety of common features in a number of fields and, thus, presenting difficulties in their differential diagnosis. The aim of the review is to identify similarities and differences between BD and BPD concerning the symptomatology, causes, course and treatment of the two disorders. A systematic electronic search of Pubmed (Medline) was conducted in order to identify all relevant scientific articles published between 1990 and 2010. The main common clinical features of BD and BPD are affective instability and impulsivity, which, however, present with quality differences in each disorder. In the field of neuroanatomy, BD and BPD demonstrate similarities such as alterations in the limbic system, as well as specific differences, such as the increase in size of the amygdala in BD and the decrease in BPD. Both disorders appear to have a significant percentage of heritability, but environmental factors seem to hold an important role in BPD, in particular. Both BD and BPD are affected by alterations in the dopaminergic and serotonergic system. Fuctionability and prognosis are slightly worse for BPD. Concerning medication treatment, antidepressants are considered effective in BPD, whereas mood stabilizers are the main treatment of choice in BD. The effectiveness of a variety of psychotherapeutic methods is still under research for both disorders. Despite the similarities and differences already being traced in clinical and biological fields, the relationship of the two disorders has not yet been thoroughly defined.
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Affiliation(s)
- Diomidis Antoniadis
- Department of Psychiatry, School of Medicine, Democritus University of Thrace, Alexandroupoli, Greece.
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47
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Brain structure and function in borderline personality disorder. Brain Struct Funct 2012; 217:767-82. [DOI: 10.1007/s00429-012-0379-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2011] [Accepted: 01/04/2012] [Indexed: 01/18/2023]
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Abstract
The dopaminergic system is involved in the regulation of aggression in many species, especially via dopamine (DA) D1 and D2 receptor pathways. To investigate heritable differences in this regulation, 2 high aggressive strains [Dekalb XL (DXL) and low group egg productivity and survivability (LGPS)] and one low aggressive strain (low group egg productivity and survivability; HGPS) of laying hens were used in the study. The HGPS and LGPS lines were diversely selected using group selection for high and low group production and survivability. The DXL line is a commercial line selected through individual selection based on egg production. Heritable differences in aggressive propensity between the strains have been previously assessed. The birds were pair housed within the same strain and labeled as dominant or subordinate based on behavioral observation. For both experiments 1 and 2, behavioral analysis was performed on all 3 strains whereas neurotransmitter analysis was performed only on the most aggressive (DXL) and least aggressive (HGPS) strains. In experiment 1, the subordinate birds were treated with D1 agonist, D2 agonist, or saline controls (n = 12). In experiment 2, the dominant birds from a separate flock were treated with D1 antagonist, D2 antagonist, or saline controls (n = 12). Treatment-associated changes in aggressive behaviors and central neurotransmitters were measured. Aggression was increased in all strains in response to D1 agonism but increased only in the less aggressive HGPS birds with D2 agonism. Aggression was decreased and hypothalamic serotonin and epinephrine were increased in birds from all strains treated with D2 receptor antagonist. The D1 receptor antagonism elicited different behavioral and neurotransmitter responses based on the aggressive phenotype of the genetic strains. Aggressive strains DXL and LGPS but not the HGPS strain decreased aggressiveness following antagonism of the D1 receptor. The data show evidence for distinct neurotransmitter regulation of aggression in high and low aggressive strains of hens through different receptor systems. These chicken lines could provide new animal models for the biomedical investigation of the genetic basis of aggression.
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Affiliation(s)
- R L Dennis
- Livestock Behavior Research Unit, USDA-ARS, West Lafayette, IN 47907, USA
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49
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Barrocas AL, Jenness JL, Davis TS, Oppenheimer CW, Technow JR, Gulley LD, Badanes LS, Hankin BL. Developmental perspectives on vulnerability to nonsuicidal self-injury in youth. ADVANCES IN CHILD DEVELOPMENT AND BEHAVIOR 2011; 40:301-36. [PMID: 21887965 DOI: 10.1016/b978-0-12-386491-8.00008-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Nonsuicidal self-injury (NSSI) is defined as intentionally causing bodily harm to oneself without the intent to kill oneself. Recently, there has been an increase in research aimed at understanding why individuals, especially youth and young adults, engage in NSSI. This chapter explores the emergence and maintenance of NSSI from a developmental perspective. Epidemiological research suggests that rates of NSSI increase dramatically from early adolescence to young adulthood. No study has investigated NSSI in youth younger than age 10. Current understanding of how emotion and cognitions as well as interpersonal processes play a role in the emergence and maintenance of NSSI is explored. Further, the role of biology (e.g., neurological underpinnings, genetic associations, HPA-axis functioning) on NSSI is explored. Throughout the chapter, particular limitations (e.g., sample selection, measurement issues) in the extant corpus of knowledge are highlighted. Finally, we consider future research directions that may inform developmentally sensitive understanding of the proximal and distal risk factors that may affect the emergence and maintenance of NSSI across the life span.
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Affiliation(s)
- Andrea L Barrocas
- Department of Psychology, University of Denver, Denver, Colorado, USA
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50
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Schuermann B, Kathmann N, Stiglmayr C, Renneberg B, Endrass T. Impaired decision making and feedback evaluation in borderline personality disorder. Psychol Med 2011; 41:1917-1927. [PMID: 21262034 DOI: 10.1017/s003329171000262x] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Increased impulsivity is considered to be a core characteristic of borderline personality disorder (BPD) and has been shown to play a significant role in decision making and planning. Neuropsychological studies in BPD revealed impairments of executive functions, and it is assumed that these deficits are related to altered feedback processing. However, research on executive functions in BPD is still limited and the underlying deficits remain an open question. The present study, therefore, explored whether decision-making deficits are related to altered feedback evaluation in BPD. METHOD A total of 18 BPD patients and 18 matched healthy controls underwent a modified version of the Iowa Gambling Task while an electroencephalogram was recorded. Feedback processing was examined by measuring the feedback-related negativity (FRN) and the P300 as electrophysiological correlates of feedback evaluation. RESULTS Behavioural results revealed that BPD patients, relative to controls, made more risky choices and did not improve their performance. With regard to the FRN, amplitudes in BPD patients did not discriminate between positive and negative feedback information. Further, BPD patients showed reduced FRN amplitudes, which were associated with enhanced impulsivity and enhanced risk taking. In contrast, the P300 amplitudes following negative feedback were increased in BPD patients, relative to controls. CONCLUSIONS This study indicates that BPD patients are impaired in decision making, which might be related to a dysfunctional use of feedback information. Specifically, BPD patients did not learn to avoid disadvantageous selections, even though they attended to negative consequences.
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Affiliation(s)
- B Schuermann
- Humboldt-Universität zu Berlin, Berlin, Germany.
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