Mentalization based treatment for borderline personality disorder

Mentalizing is the process by which we make sense of each other and ourselves, implicitly and explicitly, in terms of subjective states and mental processes. It is a profoundly social construct in the sense that we are attentive to the mental states of those we are with, physically or psychologically. Given the generality of this definition, most mental disorders will inevitably involve some difficulties with mentalization, but it is the application of the concept to the treatment of borderline personality disorder (BPD), a common psychiatric condition with important implications for public health, that has received the most attention. Patients with BPD show reduced capacities to mentalize, which leads to problems with emotional regulation and difficulties in managing impulsivity, especially in the context of interpersonal interactions. Mentalization based treatment (MBT) is a time-limited treatment which structures interventions that promote the further development of mentalizing. It has been tested in research trials and found to be an effective treatment for BPD when delivered by mental health professionals given limited additional training and with moderate levels of supervision. This supports the general utility of MBT in the treatment of BPD within generic mental health services.Borderline personality disorder (BPD) is a complex and serious mental disorder characterized by a pervasive pattern of difficulties with emotion regulation and impulse control, and instability both in relationships and in selfimage 1. It represents a serious public health problem, because it is associated with suicide attempts and self harm, both of which are consistent targets of mental health services. Recurrent suicidal behaviour is reported in 69-80% of patients with BPD, and suicide rates are estimated to be up to 10% 2. BPD is a common condition that is thought to occur globally with a prevalence of 0.2-1.8% in the general population 3. Higher prevalence rates are found in clinical populations. Moran et al 4 found a prevalence rate of 4-6% among primary care attenders, suggesting that people with BPD are more likely to visit their general practitioner. Chanen et al 5 reported a prevalence rate of 11% in adolescent outpatients and 49% in adolescent inpatients. The highest prevalence has been found in people requiring the most intensive level of care, with a rate of 60-80% among patients in forensic services 6-7. The high prevalence and increased suicide rate in patients with BPD make an unassailable argument that effective treatment needs to be developed and that treatment has to be widely available. Whilst a number of treatments for BPD have been shown to be moderately effective in randomized controlled trials, it remains of considerable concern that most of them require extensive training, making them unavailable to most patients. Mentalization based treatment (MBT) was developed with this in mind. It requires relatively little additional training on top of general mental health training, and has been implemented in research studies by community mental health professionals, primarily nurses, with limited training given modest levels of supervision.     

Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder

Borderline personality disorder (BPD) is a complex psychiatric disease of increasing importance. Epigenetic alterations are hallmarks for altered gene expression and could be involved in the etiology of BPD. In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). DNA methylation was analyzed by bisulfite restriction analysis and pyrosequencing in whole blood samples of patients diagnosed with DSM-IV BPD and in controls. Aberrant methylation was not detectable using bisulfite restriction analysis, but a significantly increased methylation of HTR2A, NR3C1, MAOA, MAOB and soluble COMT (S-COMT) was revealed for BPD patients using pyrosequencing. For HTR2A the average methylation of four CpG sites was 0.8% higher in BPD patients compared to controls (p = 0.002). The average methylation of NR3C1 was 1.8% increased in BPD patients compared to controls (p = 0.0003) and was higher at 2 out of 8 CpGs (p ≤ 0.04). In females, an increased average methylation (1.5%) of MAOA was observed in BPD patients compared to controls (p = 0.046). A similar trend (1.4% higher methylation) was observed for MAOB in female BPD patients and increased methylation was significant for 1 out of 6 CpG sites. For S-COMT, a higher methylation of 2 out of 4 CpG sites was revealed in BPD patients (p ≤ 0.02). In summary, methylation signatures of several promoter regions were established and a significant increased average methylation (1.7%) occurred in blood samples of BPD patients (p < 0.0001). Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD.     

5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine_1A receptor (5-HTR_1A) gene C −1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program ' brains '. Patients who have the 5-HTR_1A gene G allele had significantly smaller amygdala volumes than C/C genotype carriers ( P  = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR_1A genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression ( P  = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR_1A gene C −1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.     

Serum cholesterol concentration and structured individual psychoanalytic psychotherapy in suicidal and non-suicidal male patients suffering from borderline personality disorder

Findings from numerous studies suggest an association between low cholesterol levels and suicidal behavior in patients with different psychiatric diagnoses. The aims of this case-control study were to test whether cholesterol levels in male suicidal patients (N=20) with borderline personality disorder (BPD) are lower than in male non-suicidal patients (N=20) with BPD and male healthy control group (N=20), and to evaluate the influence of structured individual psychoanalytic psychotherapy on suicidal behavior. The groups were matched for age and body mass index (BMI). Results showed that serum cholesterol levels did not differ significantly between suicidal and non-suicidal BPD patients and healthy controls. The level of psychopathology (measured by Brief Psychiatric Rating Scale and Hamilton Depression Rating Scale) was significantly higher in the group of suicidal patients, which indicates the importance of evaluating particular clinical symptoms in BPD, in order to prevent suicidal behavior. Non-suicidal male patients suffering from BPD received more frequently structured individual psychoanalytic psychotherapy prior to the hospitalization than suicidal group. These results emphasized the role of this type of psychotherapy in preventing suicidal behavior in BPD patients.     

Dermatoglyphic analysis as a diagnostic tool in Wilson disease?

Dermatoglyphic analysis was performed in a family with 3 children with Wilson disease. With our findings we could not confirm the results published in two earlier papers by other authors who noted a positive relation between Wilson disease and an increased number of whorls. The practical significance of the findings is discussed.     

Borderline personality disorder and childhood maltreatment: a genome‐wide methylation analysis

Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole‐genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124‐3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124‐3 that was significantly associated with BPD and severity of childhood maltreatment. miR124‐3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome‐wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.     

The personality traits and social characteristics of Croatian heroin addicts and cannabis users

The purpose of this study was to investigate differences in social characteristics (level of education, working and family status, and criminal record) between heroin addicts, cannabis users and a control group. Additional goal was to explore the possibility of discerning subjects of different addiction status (of both gender) based on their scores on Eysenck Personality Questionnaire (EPQ). In comparison to the control group, heroin addicts and cannabis users had lower level of education, were more frequently unemployed and with criminal record, and more often came from dysfunctional families. In cannabis users the frequency of these characteristics was generally lower than in heroin addicts. Proportion of correct classification of subjects in groups of different addiction status based on the EPQ scores was 23.3% for males (higher than by chance alone), and 30% for females.     

Dermatoglyphic characters and physique: A correlation study

The association of anthropometrics, particularly hand measurements, with dermatoglyphic characters is quantified. Children with square hands exhibit higher main line indices, a-b ridge counts, and more open atd angles. Adults with broader hands have more arches. Taller individuals with larger hands present higher a-b ridge counts and leaner subjects with long narrow hands, closer atd angles. The correlation of physique and dermatoglyphics is small but if verified, suggests that at early fetal stages, factors responsible for the establishment of dermatoglyphic patterns interact with genetic determinants of adult shape that are already active.     

Influence of personality disorder on the treatment of panic disorder--comparison study

Most clinicians tend to believe that the occurrence of the anxiety disorder in comorbidity with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increasing treatment costs. The study is designed to compare the short-term effectiveness of combination of cognitive behavioral therapy and pharmacotherapy in patient suffering with panic disorder with and without personality disorder. METHOD: We compare the efficacy of 6th week therapeutic program and 6th week follow up in patients suffering with panic disorder and/or agoraphobia and comorbid personality disorder (29 patients) and panic disorder and/or agoraphobia without comorbid personality disorder (31 patients). Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI and support with psychological methods: IPDE, MCMI-III and TCI. Patients were treated with CBT and psychopharmacs. They were regularly assessed in week 0, 2, 4, 6 and 12 by an independent reviewer on the CGI (Clinical Global Improvement) for severity and change, PDSS (Panic Disorder Severity Scale), HAMA (Hamilton Anxiety Rating Scale), SDS (Sheehan Disability Scale), HDRS (Hamilton Depression Rating Scale), and in self-assessments BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). RESULTS: A combination of CBT and pharmacotherapy proved to be the effective treatment of patients suffering with panic disorder and/or agoraphobia with or without comorbid personality disorder. The 12th week treatment efficacy in the patients with panic disorder without personality disorder had been showed significantly better compared with the group with panic disorder comorbid with personality disorder in CGI and specific inventory for panic disorder--PDSS. Also the scores in depression inventories HDRS and BDI showed significantly higher decrease during the treatment comparing with group without personality disorder. But the treatment effect between groups did not differ in objective anxiety scale HAMA, and subjective anxiety scale BAI.     

Dermatoglyphic study among sex and other crime convicts

An attempt was made to investigate dermatoglyphic variation between four sex-crimes (SC) and four sex and other crime (SOC) convicts. These were compared with 10 endogamous and 11 penal populations. The results indicate that the two closely related sex crime cases IPC-363 and IPC 366 («kidnap» and «abducting») show wide differences in dermatoglyphic characters. A comparison of sex crimes with sex and other crime cases showed least differences in the case of IPC-363, IPC-363 KC and in IPC 366 and IPC-366 AC but wide differences in IPC-354 («molestation») cases. The dendrograms suggest that the eight sex crime cases cluster together and are different from other endogamous and penal populations. The significant low mean finger ridge count observed in the case of IPC-366 is in agreement with other studies, suggesting a strong association between crime (sex) and dermatoglyphics.     

Activation of caspases in lymphocytes of patients with borderline personality disorders

Activities of caspases involved in cell death have been investigated in lymphocytes of patients with borderline personality disorders (BPD). In the group of patients with organic mental disorders (OMD) caspase activity decreased in a depressive disorder and increased in an anxiety disorder, thus suggesting activation of apoptosis in lymphocytes of patients with the anxiety disorder. Caspase activities differed in lymphocytes of OMD patients with the depressive disorder and a recurrent depressive disorder. In BPD patients with OMD lymphocyte caspase activity was higher thus indicating activation of apoptosis in these cells. Results can be used for specification of mechanisms of pathogenesis of mental disorders and search for new markers of these diseases.     

Dimensional models of personality disorder

There is little doubt that someday the classification of personality disorder will be dimensional. The failures of the categorical model are so many and are so well established that it is difficult to imagine that this model will ultimately survive. This paper provides a brief discussion of the major alternative proposals for a dimensional classification of personality disorder. It is possible that the authors of a future edition of a psychiatric diagnostic manual will simply choose one of these alternative proposals. However, the ideal solution might be to develop a common, integrative representation including the important contributions of each of the models.     

Dermatoglyphic analysis of different types of bronchopulmonary carcinoma

This research was supported by the Ministry for Science and Technology of the Republic of Croatia, under the title “Anthropological investigations of the Population Structure of Croatia” (Project: 01960101). In this investigation of etiology of carcinoma the discriminant analysis and Mahalonobis D² biological distance was carried out on the sample of a group of 301 patients with four different histological types of bronchopulmonary carcinoma and compared with 400 phenotypically healthy persons. Prints of dermatoglyphs were taken for 18 quantitative dermatoglyphic traits on fingers and palms. Discriminant analysis has shown palmar variables as primary discriminating variables between the patients suffering from different types of carcinoma and phenotypically healthy controls, and between the group of patients suffering from carcinoma. Discriminant classification is very high between patients suffering from carcinoma and phenotypically healthy controls in males and in females. Mahalanobis D² biological distances show differences between the group of cancers and phenotypically healthy controls. This findings clearly show the genetical predisposition for the disease, but genetic interpretations do not exclude environmental influences during the period of early intrauterine life in patients suffering from carcinoma.     

Dermatoglyphic analysis of fetuses with chromosomal abnormalities.

I applied Okajima's technique of exposing the dermal surface by chemical and mechanical treatment followed by toluidine blue stain to inspect the dermatoglyphic features of hands of aborted human fetuses with chromosomal abnormalities. The dermatoglyphic patterns of five fetuses, three with Down syndrome, one with 5p--, and one with 18 trisomy, were analyzed to determine whether the patterns were sufficiently specific to be used for diagnostic purposes. Apparently unique patterns were obtained. Observation of the dermal surface suggested that the developmental sequence of the ridges in fetuses with chromosomal disorders was retarded by more than 2 weeks as compared with that of normal fetuses of th same gestation.