Katja Bertsch

Oxytocin and Reduction of Social Threat Hypersensitivity in Women With Borderline Personality Disorder

OBJECTIVE Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration. METHOD In a randomized placebo-controlled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of the amygdala to angry and fearful compared with happy facial expressions. RESULTS Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration. CONCLUSIONS Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.

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.

Resting cerebral blood flow, attention, and aging.

Aging is accompanied by a decline of fluid cognitive functions, e.g., a slowing of information processing, working memory, and division of attention. This is at least partly due to structural and functional changes in the aging brain. Although a decrement of resting cerebral blood flow (CBF) has been positively associated with cognitive functions in patients with brain diseases, studies with healthy participants have revealed inconsistent results. Therefore, we investigated the relation between resting cerebral blood flow and cognitive functions (tonic and phasic alertness, selective and divided attention) in two samples of healthy young and older participants. We found higher resting CBF and better cognitive performances in the young than in the older sample. In addition, resting CBF was inversely correlated with selective attention in the young and with tonic alertness in the elderly participants. This finding is discussed with regard to the neural efficiency hypothesis of human intelligence.

Stability of heart rate variability indices reflecting parasympathetic activity

Heart rate variability (HRV) is a measure of autonomic influences on heart rate that has frequently been used as a transsituationally consistent biomarker for cardiovascular health and emotional or cognitive functions. The psychometric properties of HRV however remain unclear. In the present study, we examined the reliability and temporal stability of parasympathetic HRV measures and estimated the portion of variance explained by transsituationally consistent trait variance and by effects of the situation and person-situation interaction with structural equation modeling. The results show good reliability of indices reflecting central parasympathetic control over heart rate and that about 40% of the variance of a single HRV measurement can be explained by effects of the situation and person-situation interaction. An aggregation across at least two measurements may be recommended when using HRV as a transsituationally consistent biomarker or trait.

Mechanisms of disturbed emotion processing and social interaction in borderline personality disorder: state of knowledge and research agenda of the German Clinical Research Unit

The last two decades have seen a strong rise in empirical research in the mechanisms of emotion dysregulation in borderline personality disorder. Major findings comprise structural as well as functional alterations of brain regions involved in emotion processing, such as amygdala, insula, and prefrontal regions. In addition, more specific mechanisms of disturbed emotion regulation, e.g. related to pain and dissociation, have been identified. Most recently, social interaction problems and their underlying neurobiological mechanisms, e.g. disturbed trust or hypersensitivity to social rejection, have become a major focus of BPD research. This article covers the current state of knowledge and related relevant research goals. The first part presents a review of the literature. The second part delineates important open questions to be addressed in future studies. The third part describes the research agenda for a large German center grant focusing on mechanisms of emotion dysregulation in BPD.

Morphometric differences in central stress-regulating structures between women with and without borderline personality disorder.

BACKGROUND Experiences of early life stress, increased psychological arousal and the bodys physiologic stress response seem to play an important role in the pathogenesis and maintenance of borderline personality disorder (BPD). In the present study, we investigated alterations in grey matter of central stress-regulating structures in female patients with BPD. METHODS We examined T1-weighted structural magnetic resonance imaging scans of unmedicated, right-handed female patients with BPD (according to DSM-IV criteria) and healthy controls matched for age, intelligence and education using fully automated DARTEL voxel-based morphometry. Our regions of interest analyses included the hippocampus, amygdala, anterior cingulate cortex (ACC) and hypothalamus. RESULTS We enrolled 30 patients and 33 controls in our study. The grey matter of patients with BPD was reduced in the hippocampus, but increased in the hypothalamus compared with healthy participants. Hypothalamic volume correlated positively with the history of traumatization in patients with BPD. No significant alterations were found in the amygdala and ACC. LIMITATIONS This study is limited by the lack of measures of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol levels. Furthermore, moderate sample size and comorbid disorders need to be considered. CONCLUSION Our findings provide new evidence for grey matter alterations in the hypothalamus and replicate previously reported decrements in hippocampal volume in patients with BPD. Understanding the role of the hypothalamus and other central stress-regulating structures could help us to further understand the neurobiological underpinnings of this complex disorder.

Brain volumes differ between diagnostic groups of violent criminal offenders.

Studies on structural abnormalities in antisocial individuals have reported inconsistent results, possibly due to inhomogeneous samples, calling for an investigation of brain alterations in psychopathologically stratified subgroups. We explored structural differences between antisocial offenders with either borderline personality disorder (ASPD-BPD) or high psychopathic traits (ASPD-PP) and healthy controls (CON) using region-of-interest-based and voxel-based morphometry approaches. Besides common distinct clusters of reduced gray matter volumes within the frontal pole and occipital cortex, there was remarkably little overlap in the regional distribution of brain abnormalities in ASPD-BPD and ASPD-PP, when compared to CON. Specific alterations of ASPD-BPD were detected in orbitofrontal and ventromedial prefrontal cortex regions subserving emotion regulation and reactive aggression and the temporal pole, which is involved in the interpretation of other peoples’ motives. Volumetric reductions in ASPD-PP were most significant in midline cortical areas involved in the processing of self-referential information and self-reflection (i.e., dorsomedial prefrontal cortex, posterior cingulate/precuneus) and recognizing emotions of others (postcentral gyrus) and could reflect neural correlates of the psychopathic core features of callousness and poor moral judgment. The findings of this first exploratory study therefore may reflect correlates of prominent psychopathological differences between the two criminal offender groups, which have to be replicated in larger samples.

The social-cognitive basis of personality disorders

Purpose of review The review summarizes recent results on abnormalities in social cognition in patients with personality disorders that predispose them to develop dysfunctional interaction with others. The review starts with more basic social cognition processes, such as emotion recognition and reactions to social exclusion that are followed by more complex processes such as cognitive and affective empathy. Recent findings The deficits in social cognition depend on the particular function that is investigated and is strongly associated with characteristic symptoms of particular personality disorders. Thus, patients with borderline personality disorder are hypersensitive for social threat, they show deficits in cognitive empathy and high emotion contagion, that is, they share emotions of others without properly discriminating between ones own feelings and those of others. Psychopaths are characterized by deficiency in facial fear recognition and emotional empathy similar to patients with narcissistic personality disorder. Studies on social cognition in cluster A and C personality disorders are sparse. Summary Research indicates deficits in social cognition in patients with personality disorders, but more research is needed to investigate social cognition in cluster A and C personality disorders and to compare deficits in social cognitive functions across personality disorders.

Exogenous cortisol enhances aggressive behavior in females, but not in males

The hypothalamic-pituitary-adrenal (HPA) axis plays a major role in the development, elicitation, and enhancement of aggressive behavior in animals. Increasing evidence suggests that this is also true for humans. Here, we report on a study of the role of basal and acute HPA axis activity in a sample of 48 healthy male and female adults. We pharmacologically enhanced cortisol levels and used the Taylor Aggression Paradigm (TAP) to induce and measure aggression (divided into three blocks). Participants either received an oral dose of 20 mg hydrocortisone (cortisol group) or a placebo (placebo group). Half of each group received high or low levels of provocation with the TAP, respectively. Before, we assessed the cortisol awakening response as a trait measure of basal HPA axis activity. Participants in the cortisol group reacted more aggressively in the third block of the TAP compared to the placebo group. Furthermore, gender interacted with treatment: only females, but not males showed enhanced aggressive behavior after cortisol administration. There was no significant difference in males between the placebo and cortisol group. Basal HPA axis activity was negatively related to aggressive behavior, but again only in females and most strongly within the placebo group. This study provides the first evidence for a causal involvement of acute HPA axis activation in aggressive behavior in humans.

Aggression in borderline personality disorder: a multidimensional model

This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach.