Decreased oxytocin levels related to social cognition impairment in borderline personality disorder.

INTRODUCTION: Dysfunctions in the oxytocin system have been reported in patients with borderline personality disorder (BPD). Deficits could be related to interpersonal hypersensitivity, which has been previously associated with failures in social cognition (SC) in this disorder, especially in Theory of Mind (ToM) skills. The aim of this work is to study the links between the oxytocin system and SC impairments in patients with BPD. METHOD: Plasma oxytocin levels (OXT) and protein expression of oxytocin receptors in blood mononuclear cells (OXTR) were examined in 33 patients with a diagnosis of BPD (age: M 28.85, DT = 8.83). Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). Statistical associations between biochemical factors and different response errors in MASC were analyzed through generalized linear regression controlling for relevant clinical factors. RESULTS: Generalized linear regression showed a significant relationship between lower OXTR and overmentalization in BPD patients (OR = 0.90). CONCLUSIONS: This work supports the relationship between alterations in the oxytocin system and ToM impairments observed in BPD patients, enhancing the search for endophenotypes related to the phenotypic features of the disorder to improve current clinical knowledge and address more specific therapeutic targets.

Hypothalamic-pituitary-thyroid axis function in female adolescent nonsuicidal self-injury and its association with comorbid borderline personality disorder and depression.

OBJECTIVES: Behavioral disturbances in adolescence are potentially linked to aberrant functioning of the thyroid gland. Accordingly, alterations of the hypothalamic-pituitary-thyroid (HPT) axis might impact psychopathological development. Yet corresponding research in adolescents with nonsuicidal self-injury (NSSI) and comorbid mental disorders is scarce. METHODS: The present study examined HPT axis functioning in adolescents with NSSI compared to healthy controls (HC) using blood-based assays of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and the ratio of these hormones (fT3/fT4 ratio). Cortisol was additionally examined to contrast HPT axis functioning with a well-established biomarker of stress responsivity. Moreover, associations between clinical characteristics, HPT axis and HPA axis functioning were investigated. Female adolescents meeting NSSI criteria according to DSM-5 criteria (n = 117) were compared to adolescent HC (n = 41). Standardized serum-based endocrinological assays and interview- and questionnaire-based psychiatric assessments were used. Smoking status was included as covariate for all analyses. RESULTS: NSSI patients displayed altered HPT axis functioning as fT3/fT4 ratio values were blunted in comparison to HC. Negative correlations were further present between fT3, fT3/fT4 ratio and severity of BPD symptoms, depression scores and symptomatic distress. TSH correlated negatively with severity of BPD symptoms and symptomatic distress exclusively. Cortisol values differed neither significantly between experimental groups nor correlated significantly with clinical characteristics. CONCLUSIONS: Longitudinal examinations, assessing links between psychopathology and endocrinological alterations, are warranted to address potential clinical implications of thyroid markers in child and adolescent psychiatry.

Inflammatory and antioxidant pathway dysfunction in borderline personality disorder.

INTRODUCTION: This study investigates the alteration of the inflammatory/oxidative pathway in patients with borderline personality disorder (BPD) and its relationship with clinical features of the disorder. METHODS: 49 BPD patients and 33 healthy control subjects were studied. Plasma levels of TBARS, nitrites, and the antioxidant enzymes CAT, GPx and SOD were measured. In addition, peripheral blood mononuclear cells were obtained to investigate levels of intracellular components of the inflammatory/oxidative pathway including the IκBα, NFκB, iNOS, COX2, Keap1, NQO1, and HO1. Western Blot and ELISA were used to measure protein expression. Patients were assessed for different clinical dimensions of BPD with scales for depression, anxiety, impulsivity and functioning. RESULTS: A significant decrease of IκBα levels and a significant increase of inflammatory factors, including NFκB, COX2 and iNOS levels were found in patients. On the other hand, a significant decrease was observed for all antioxidant enzymes in patients with BPD, except for HO1. The inflammatory factor NFκB showed a significant positive correlation with impulsivity scores. CONCLUSIONS: Patients with BPD presented an increased activation of several components of the inflammatory pathways, as well as an inhibition of the antioxidant path. These alterations appear partially correlated with the impulsivity scores in these patients.

[Oxytocin and maltreatment potential : Influence of maternal depression, borderline personality disorder and experience of early childhood maltreatment]. / Oxytocin und Misshandlungspotenzial : Einfluss von mütterlicher Depression, Borderline-Persönlichkeitsstörung und frühkindlicher Misshandlungserfahrung.

BACKGROUND: The "empathy hormone" oxytocin (OXT) is associated with social interaction and parent-child interaction. Mothers with mental stress factors, e.g., history of depression, borderline personality disorder or early life maltreatment in their own childhood often show distinct maternal behavior. The objectives of the study were (1) to examine the association between these three stress factors and maternal OXT within one analysis. (2) Moreover, OXT was tested as a potential mediator for the association between maternal experience of early childhood maltreatment and abuse potential against their own child. METHODS: Plasma OXT concentrations of 52 mothers during the follicular phase were collated (healthy control mothers n = 22, history of depression n = 23, borderline personality disorder n = 7). The maternal history of psychiatric disorders and experiences of early childhood maltreatment were examined via interviews. Regression and mediation analyses were applied to answer the research questions. RESULTS: Early childhood maltreatment was associated with reduced plasma OXT; however, maternal history of depression and borderline personality disorder were not related to OXT concentrations. In particular, having experienced parental antipathy in one's own childhood was associated with reduced OXT levels but OXT did not mediate the association between maternal early childhood experiences of maltreatment and abuse potential of their own child. CONCLUSION: In the present study alterations in plasma OXT concentrations were not associated with psychiatric disorders, such as a history of depression or borderline personality disorder but more with a potential etiological factor of these disorders, i.e. experience of maltreatment in their own childhood.

Bipolar affective disorder and borderline personality disorder: Differentiation based on the history of early life stress and psychoneuroendocrine measures.

INTRODUCTION: Borderline Personality Disorder (BPD) and Bipolar Affective Disorder (BD) have clinical characteristics in common which often make their differential diagnosis difficult. The history of early life stress (ELS) may be a differentiating factor between BPD and BD, as well as its association with clinical manifestations and specific neuroendocrine responses in each of these diagnoses. OBJECTIVE: Assessing and comparing patients with BD and BPD for factors related to symptomatology, etiopathogenesis and neuroendocrine markers. METHODOLOGY: The study sample consisted of 51 women, divided into 3 groups: patients with a clinical diagnosis of BPD (n = 20) and BD (n = 16) and healthy controls (HC, n = 15). Standardized instruments were used for the clinical evaluation, while the history of ELS was quantified with the Childhood Trauma Questionnaire (CTQ), and classified according to the subtypes: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. The functioning of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring a single plasma cortisol sample. RESULTS: Patients with BPD presented with more severe psychiatric symptoms of: anxiety, impulsivity, depression, hopelessness and suicidal ideation than those with BD. The history of ELS was identified as significantly more prevalent and more severe in patients (BPD and BP) than in HC. Emotional abuse, emotional neglect and physical neglect also showed differences and were higher in BPD than BD patients. BPD patients had greater severity of ELS overall and in the subtypes of emotional abuse, emotional neglect and physical neglect than BD patients. The presence of ELS in patients with BPD and BP showed significant difference with lower cortisol levels when compared to HC. The endocrine evaluation showed no significant differences between the diagnoses of BPD and BD. Cortisol measured in patients with BPD was significantly lower compared to HC in the presence of emotional neglect and physical neglect. A significant negative correlation between the severity of hopelessness vs cortisol; and physical neglect vs cortisol were found in BPD with ELS. The single cortisol sample showed a significant and opposite correlations in the sexual abuse diagnosis-related groups, being a negative correlation in BD and positive in BPD. DISCUSSION: Considering the need for a multi-factorial analysis, the differential diagnosis between BPD and BD can be facilitated by the study of psychiatric symptoms, which are more severe in the BPD patients with a history of early life stress. The function of the HPA axis assessed by this cortisol measure suggests differences between BPD and BP with ELS history. CONCLUSION: The integrated analysis of psychopathology, ELS and neuroendocrine function may provide useful indicators to differentiate BPD and BD diagnoses. These preliminary data need to be replicated in a more significant sample with improved and multiple assessments of HPA axis activity.

The neurobiology of social deficits in female patients with borderline personality disorder: The importance of oxytocin.

BACKGROUND: Social deficits and emotional dysregulation have been suggested as explanations for the relational difficulties experienced by patients with borderline personality disorder (BPD). The neuropeptide oxytocin (OXT) is a possible neurobiological underpinning of these adversities, and this study examines possible correlations between BPD symptomatology and serum OXT. METHODS: Thirty-eight female participants (BPD group n = 18, matched control group n = 20) with a mean age of 29.5 years (standard deviation 9.2) were assessed for personality disorders, general psychopathology, childhood trauma and perceived stress. OXT was measured in serum samples. RESULTS: We found no significant difference between patient and control group in terms of OXT levels. However, post hoc analysis showed a relationship in the patient group between civil status and OXT (p < 0.05), indicating higher levels of OXT for patients in a romantic relationship. DISCUSSION: The idea of OXT as a pro-social love hormone is perhaps too simplistic, and factors like attachment style, exposure to trauma and psychiatric disorders must be considered in order to understand its diverse functions. CONCLUSIONS: Contrary to our expectations, we did not find lower serum OXT levels in the BPD group. However, BPD patients in a romantic relationship had higher levels of serum OXT than single BPD patients. Copyright © 2017 John Wiley & Sons, Ltd.

Increased serum prolactin in borderline personality disorder.

Although there is an important interaction between serotonergic system, prolactin and suicidal behavior, and impulsivity, no investigation examined the prolactin values in borderline personality disorder in which suicidal behavior and impulsivity are core symptom dimensions. In this context, in the present investigation, we planned to measure serum prolactin levels in the patients with borderline personality disorder. The study comprised 15 patients with borderline personality disorder and 15 healthy controls. Prolactin values were measured in both patients and control subjects. The patients had abnormally higher mean value of prolactin compared to those of healthy controls (48.66 ± 36.48 mg/dl for patients vs. 15.20 ± 7.81 mg/dl for healthy controls). There was no correlation between prolactin values and any demographic variables for both the patients and control subjects. In conclusion, our present results suggest that prolactin values increased in the patients with borderline personality disorder and are required to be replicated by more comprehensive and detailed further studies to decipher the exact roles of prolactin increase.

Thyroid hormones and adult interpersonal violence among women with borderline personality disorder.

Elevated T3 levels have been reported in men with antisocial behavior. The aim of the present study was to investigate the relationship between thyroid hormones and expressed adult interpersonal violence in female patients with borderline personality disorder (BPD). Furthermore, expressed adult interpersonal violence in female BPD patients was compared to healthy female controls. A total of 92 clinically euthyroid women with BPD and 57 healthy women were assessed with the Karolinska Interpersonal Violence Scales (KIVS). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays in patients. Plasma cortisol was also measured. Among females with BPD, expressed interpersonal violence as an adult showed a significant positive correlation with the T3 levels. The mean expression of interpersonal violence as an adult was significantly higher in BPD patients as compared to healthy controls. The multiple regression model indicated that two independent predictors of KIVS expressed interpersonal violence as an adult: T3 and comorbid diagnosis of alcohol abuse. Association between T3 levels and violent/aggressive behavior earlier reported exclusively in male samples may be valid also in females with BPD.

Male inmate profiles and their biological correlates.

OBJECTIVE: Borderline and antisocial personality disorders (PDs) share common clinical features (impulsivity, aggressiveness, substance use disorders [SUDs], and suicidal behaviours) that are greatly overrepresented in prison populations. These disorders have been associated biologically with testosterone and cortisol levels. However, the associations are ambiguous and the subject of controversy, perhaps because these heterogeneous disorders have been addressed as unitary constructs. A consideration of profiles of people, rather than of exclusive diagnoses, might yield clearer relationships. METHODS: In our study, multiple correspondence analysis and cluster analysis were employed to identify subgroups among 545 newly convicted inmates. The groups were then compared in terms of clinical features and biological markers, including levels of cortisol, testosterone, estradiol, progesterone, and sulfoconjugated dehydroepiandrosterone (DHEA-S). RESULTS: Four clusters with differing psychiatric, criminal, and biological profiles emerged. Clinically, one group had intermediate scores for each of the tested clinical features. Another group comprised people with little comorbidity. Two others displayed severe impulsivity, PD, and SUD. Biologically, cortisol levels were lowest in the last 2 groups and highest in the group with less comorbidity. In keeping with previous findings reported in the literature, testosterone was higher in a younger population with severe psychiatric symptoms. However, some apparently comparable behavioural outcomes were found to be related to distinct biological profiles. No differences were observed for estradiol, progesterone, or DHEA-S levels. CONCLUSIONS: The results not only confirm the importance of biological markers in the study of personality features but also demonstrate the need to consider the role of comorbidities and steroid coregulation.

Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder.

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to such mental-illness phenotypes as eating disorders. Numerous studies have shown an association between bulimia nervosa (BN) and variations in brain-derived neurotrophic factor (BDNF). BDNF has also been linked to borderline personality disorder (BPD) and to such traits as reward dependence. We examined the extent to which BDNF methylation corresponded to bulimic or normal-eater status, and also to the presence of comorbid borderline personality disorder (BPD) and childhood abuse. Our sample consisted of 64 women with BN and 32 normal-eater (NE) control women. Participants were assessed for eating-disorder symptoms, comorbid psychopathology, and childhood trauma, and then they were required to provide blood samples for methylation analyses. We observed a significant site×group (BN vs. NE) interaction indicating that women with BN showed increases in methylation at specific regions of the BDNF promoter. Furthermore, examining effects of childhood abuse and BPD, we observed significant site×group interactions such that groups composed of individuals with childhood abuse or BPD had particularly high levels of methylation at selected CpG sites. Our findings suggest that BN, especially when co-occurring with childhood abuse or BPD, is associated with a propensity towards elevated methylation at specific BDNF promoter region sites. These findings imply that hypermethylation of the BDNF gene may be related to eating disorder status, developmental stress exposure, and comorbid psychopathology.

Diazepam binding inhibitor and dehydroepiandrosterone sulphate plasma levels in borderline personality disorder adolescents.

BACKGROUND: Borderline personality disorder (BPD) patients display a complex and heterogeneous clinical phenotype that plausibly implies variable underlying pathogenic mechanisms. A dysregulation of peripheral benzodiazepine receptors has previously been shown in BPD peripheral tissues, implying possible alterations of its ligand, the diazepam binding inhibitor (DBI) or of the downstream products of its activation, i.e. neuroactive steroids. METHODS: The aim of this work consisted in assessing, by ELISA, fasting plasma levels of DBI and dehydroepiandrosterone sulphate (DHEA-S), including cortisol and the cortisol-to-DHEA-S molar ratio (CDR), in 17 BPD adolescents versus 13 healthy controls, testing the possibility that clinical scales related to depressive or anxious traits (CDI, STAI-Y) or to disease severity (BPDCL) might be associated with a selective dysregulation of these parameters. RESULTS: DBI plasma levels were unchanged, while DHEA-S ones were significantly increased (approx. 70%) and the CDR decreased in BPD patients. No meaningful correlations with clinical variables emerged. CONCLUSION: Our results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels and that DHEA-S might represent a generalized trait marker for the altered stress response that is associated with this disorder.

Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders.

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.

C-reactive protein, pre- and postdexamethasone cortisol levels in post-traumatic stress disorder.

BACKGROUND: Dysregulations of the hypothalamic-pituitary-adrenal axis may impact inflammatory processes in post-traumatic stress disorder (PTSD), possibly resulting in a low-grade inflammation as reflected by elevated levels of C-reactive protein (CRP). METHODS: Serum CRP levels and salivary cortisol before and after the dexamethasone suppression test (DST) were assessed in 50 inpatients with main diagnoses PTSD, major depressive disorder or borderline personality disorder. RESULTS: A strong trend for lower CRP levels was found in PTSD positive individuals compared with patients without PTSD. CONCLUSIONS: Our study does not support the hypothesis of elevated serum CRP levels in PTSD compared with other psychiatric patients. However, a dysbalanced immune system with suppressed CRP might contribute to the elevated somatic comorbidity in PTSD.

Reduced plasma oxytocin levels in female patients with borderline personality disorder.

The neuropeptide oxytocin is involved in social cognition and interaction across species and plays a crucial role in the regulation of affiliative behaviors. Oxytocin levels in cerebrospinal fluid (CSF), but also in plasma or urine, have been shown to be negatively associated with childhood traumata, aggressive behavior, and suicide attempts. Recently, an altered activity of the oxytocin system has been discussed to play a prominent role in borderline personality disorder (BPD), which is thought to be closely related to traumatic experiences in childhood and is characterized by (para)suicidal behaviors as well as aggressive outbursts. In the present study, we compared plasma oxytocin levels of women with and without BPD in the follicular phase and assessed the relationship between oxytocin concentrations and childhood traumata. Women diagnosed with BPD had significantly reduced oxytocin concentrations, even after controlling for estrogen, progesterone, and contraceptive intake. In addition, plasma oxytocin correlated negatively with experiences of childhood traumata, in particular with emotional neglect and abuse. The results of mediation analyses do not support a model of oxytocin being a prominent mediator in the link between childhood trauma and BPD. Thus, the findings indicate dysregulations in the oxytocin system of patients diagnosed with BPD with more longitudinal research being necessary to disentangle the relationship between childhood adversities, oxytocin system, and psychopathology.

Activation of the cholinergic anti-inflammatory system in peripheral blood mononuclear cells from patients with borderline personality disorder.

A case-control study including patients (n = 20) with Borderline Personality Disorder (BPD) and healthy controls (n = 33) was carried out. To avoid interferences of other clinical conditions on biological findings, patients were free of current major depressive episodes or substance dependence disorders, and had no life history of schizophrenia, bipolar or neuropsychiatric disorders. Patients were free of medication for at least two weeks at the time of the study. Studies carried out in peripheral mononuclear blood cells and plasma evidence a systemic inflammatory condition in unstable-impulsive BPD patients. Specifically, a significant increase in some intracellular components of two main pro-inflammatory pathways such as iNOS and COX-2, as well as an increase in the plasma levels of the inflammatory cytokine IL1ß. Interestingly, patients have an increase in the protein expression of the anti-inflammatory subtype of nicotinic receptor α7nAChR. This finding may reflect a possible mechanism trying to maintain intracellular inflammation pathways under control. All together, these results describe an imbalanced, pro-inflammatory and oxidant phenotype in BPD patients independent of plasma cotinine levels. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways have interesting potential as biological markers for BPD and other generalized impulsive syndromes, specially data obtained with α7nAChR and its lack of correlation with plasma levels of nicotine metabolites. Their pharmacological modulation with receptor modulators can be a promising therapeutic target to take into account in mental health conditions associated with inflammatory or oxido/nitrosative consequences. Also, identifying at-risk individuals would be of importance for early detection and intervention in adolescent subjects before they present severe behavioural problems.

Platelet protein kinase C and brain-derived neurotrophic factor levels in borderline personality disorder patients.

Borderline personality disorder (BPD) is a prevalent and difficult to treat psychiatric condition characterized by abrupt mood swings, intense anger and depression, unstable interpersonal relationships, impulsive self-destructive behavior and a suicide rate of approximately 10%. Possible underlying molecular dysregulations in BPD have not been well explored. Protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) have both been implicated in affective disorders, but their role in BPD has not been examined. Platelets were isolated from blood obtained from 24 medication-free BPD patients and 18 healthy control subjects. PKC-α, phosphorylated-PKC-α (p-PKCα), PKC-ßII, and BDNF were measured in platelet homogenates by immunoblotting. In the males, platelet BDNF and PKC-α levels were lower in patients than controls. p-PKC-α and PKC-ßII were lower at trend levels. In the entire sample, platelet p-PKCα and PKC-α activity were lower, at a trend level, in patients compared to controls. This is the first report to our knowledge of PKC and BDNF activity in BPD and calls for replication. These findings are consistent with altered PKC and BDNF activity in a range of neuropsychiatric conditions including bipolar disorder, depression and suicide.

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.

Psychobiology of borderline personality traits related to subtypes of eating disorders: a study of platelet MAO activity.

Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating-purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating-purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge-purge patients with comorbid BPD than in binge-purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.