Generalization of fear in post-traumatic stress disorder.

Overgeneralization (i.e., the transfer of fear to stimuli not related to an aversive event) is part of alterations in associative fear learning in mental disorders. In the present experimental study, we investigated whether this holds true for post-traumatic stress disorder (PTSD) related to childhood abuse. We expected that fear generalization under experimental conditions reflects generalization of aversive stimuli to different social domains in real life. Sixty-four women with PTSD after childhood abuse and 30 healthy participants (HC) underwent a differential fear conditioning and generalization paradigm. Online risk ratings, reaction time, and fear-potentiated startle served as dependent variables. Based on the subjectively assessed generalization of triggered intrusions across different domains of life, PTSD participants were split into two groups reporting low (low-GEN) and high (high-GEN) generalization. PTSD patients reported a higher expectation of an aversive event. During fear conditioning, they assessed the risk of danger related to a safety cue slower and showed a blunted fear-potentiated startle toward the danger cue. During generalization testing, reaction time increased in the high-GEN patients and decreased in the HC group with increasing similarity of a stimulus with the conditioned safety cue. Alterations of fear learning in PTSD suggest impaired defensive responses in case of a high threat probability. Moreover, our findings bridge the gap between the generalization of aversive cues during everyday life and laboratory-based experimental parameters: impairments in the processing of cues signaling safety generalize particularly in those patients who report a spreading of PTSD symptoms across different domains of everyday life.

[Borderline personality : Alterations to brain structure and function through psychotherapy]. / Borderline-Persönlichkeitsstörung : Veränderung der Hirnstruktur und -funktion durch Psychotherapie.

BACKGROUND: There are now several scientifically evaluated psychotherapeutic methods for borderline personality disorder (BPD), all of which aim to improve the ability to regulate emotions. In recent years, there have been first studies on the neuronal correlates of the mechanisms of emotion regulation and of changes caused by psychotherapeutic interventions. METHODS: This article reviews the data on functional and structural imaging studies that examine facets of disturbed emotion regulation before and after psychotherapy. RESULTS: Although the overall database is still sparse, clinical improvement in psychotherapy appears to be associated with modulation of brain structure and function. Frontolimbic regulation circuits including the amygdala, insula, anterior cingulate cortex (ACC) and other prefrontal areas appear to be involved in these changes. An important finding is the reduction of initially increased amygdala activity after successful Dialectical Behavior Therapy (DBT). CONCLUSION: The changes shown here most probably reflect an improvement in emotion regulation capacities in BPD and demonstrate the possibility of modulating disturbed emotion regulation processes. Since long-term follow-up data are still missing, the sustainability of the suggestive improvements still has to be proven in further studies.

Delay discounting and response disinhibition under acute experimental stress in women with borderline personality disorder and adult attention deficit hyperactivity disorder.

BACKGROUND: Impulsivity is a core feature of borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD). In BPD, impulsive behavior primarily occurs under acute stress; impulse control deficits under non-stress conditions may be partly related to co-morbid ADHD. We aimed to investigate whether acute experimental stress has an impact on self-reported impulsivity, response inhibition (action withholding, action cancelation) and delay discounting in BPD compared to ADHD. METHOD: Thirty female BPD patients, 28 female ADHD patients (excluding patients with co-morbid BPD and ADHD), and 30 female healthy controls (HC) completed self-reports and behavioral measures of impulsivity (IMT, assessing action withholding; GoStop, measuring action cancelation, Delay Discounting Task) under baseline conditions and after an experimental stress induction (Mannheim Multicomponent Stress Test). RESULTS: Both patient groups reported higher impulsivity than HC, ADHD reported higher trait impulsivity than BPD. On the IMT, ADHD showed significant action-withholding deficits under both conditions, while BPD performed significantly worse than HC under stress. In BPD but not ADHD and HC, action-withholding deficits (IMT) were significantly increased under stress compared to baseline, while no group/stress effects were found for action cancelation (GoStop). Delay discounting was significantly more pronounced in BPD than in HC (no stress effect was found). CONCLUSIONS: In BPD, behavioral deficits in action withholding (but not in action cancelation) appear to be influenced by acute experimental stress. Delay discounting seems to be a general feature of BPD, independent of co-morbid ADHD and acute stress, possibly underlying typical expressions of behavioral impulsivity in the disorder.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of borderline personality disorder : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung der Borderline-Persönlichkeitsstörung : Normative Personalbedarfsermittlung.

BACKGROUND: Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well-tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure. OBJECTIVE: The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV). MATERIAL AND METHODS: The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV. RESULTS: The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %. DISCUSSION: Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness.

Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma.

BACKGROUND: Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD. METHOD: Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions. RESULTS: Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus. CONCLUSIONS: Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

Impact of stress on different components of impulsivity in borderline personality disorder.

BACKGROUND: Previous research on impulsivity in borderline personality disorder (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed during states of emotional distress and might be exaggerated by current attention deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed to investigate different components of impulsivity dependent on stress induction controlling for self-reported ADHD symptoms in BPD. METHOD. A total of 31 unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched for age, education and intelligence, completed self-reports and behavioural tasks measuring response inhibition (go/stop task) and feedback-driven decision making (Iowa Gambling Task) under resting conditions and after experimental stress induction. ADHD symptoms were included as a covariate in the analyses of behavioural impulsivity. Additionally, self-reported emotion-regulation capacities were assessed. RESULTS: BPD patients reported higher impulsive traits than HCs. During stress conditions - compared with resting conditions - self-reported impulsivity was elevated in both groups. Patients with BPD reported higher state impulsivity under both conditions and a significantly stronger stress-dependent increase in state impulsivity. On the behavioural level, BPD patients showed significantly impaired performance on the go/stop task under stress conditions, even when considering ADHD symptoms as a covariate, but not under resting conditions. No group differences on the Iowa Gambling Task were observed. Correlations between impulsivity measures and emotion-regulation capacities were observed in BPD patients. CONCLUSIONS: Findings suggest a significant impact of stress on self-perceived state impulsivity and on response disinhibition (even when considering current ADHD symptoms) in females with BPD.

Plastic modulation of PTSD resting-state networks and subjective wellbeing by EEG neurofeedback.

OBJECTIVE: Electroencephalographic (EEG) neurofeedback training has been shown to produce plastic modulations in salience network and default mode network functional connectivity in healthy individuals. In this study, we investigated whether a single session of neurofeedback training aimed at the voluntary reduction of alpha rhythm (8-12 Hz) amplitude would be related to differences in EEG network oscillations, functional MRI (fMRI) connectivity, and subjective measures of state anxiety and arousal in a group of individuals with post-traumatic stress disorder (PTSD). METHOD: Twenty-one individuals with PTSD related to childhood abuse underwent 30 min of EEG neurofeedback training preceded and followed by a resting-state fMRI scan. RESULTS: Alpha desynchronizing neurofeedback was associated with decreased alpha amplitude during training, followed by a significant increase ('rebound') in resting-state alpha synchronization. This rebound was linked to increased calmness, greater salience network connectivity with the right insula, and enhanced default mode network connectivity with bilateral posterior cingulate, right middle frontal gyrus, and left medial prefrontal cortex. CONCLUSION: Our study represents a first step in elucidating the potential neurobehavioural mechanisms mediating the effects of neurofeedback treatment on regulatory systems in PTSD. Moreover, it documents for the first time a spontaneous EEG 'rebound' after neurofeedback, pointing to homeostatic/compensatory mechanisms operating in the brain.

[Importance of neurobiology for modular psychotherapy]. / Bedeutung der Neurobiologie für die modulare Psychotherapie.

In the context of continuing education in psychiatry and psychotherapy, modular psychotherapy is of special importance. In modular psychotherapy, general interventions, e.g. for regulation of emotions, have an important function. In this review examples are given to describe the importance of neurobiology for the understanding and the improvement of these mechanisms. In addition, the use of neurobiological investigations within classical psychotherapy trials in the fields of borderline personality disorder and posttraumatic stress disorder will be depicted.

Influence of emotional distraction on working memory performance in borderline personality disorder.

BACKGROUND: Emotion dysregulation, characterized by heightened emotional arousal and increased emotional sensitivity, is a core feature of borderline personality disorder (BPD). Although current theories emphasize the disruptive potential of negative emotions on cognitive functioning in BPD, behavioral and neurobiological data on this relationship are still lacking. METHOD: Using functional magnetic resonance imaging (fMRI), neural activity was investigated in 22 unmedicated BPD patients and 22 healthy participants (matched for age, education and intelligence) performing an adapted Sternberg working memory task, while being distracted by emotional (negatively arousing) and neutral pictures from the International Affective Picture System (IAPS). RESULTS: Emotional distraction was associated with significantly higher activation in the amygdala and decreased activation in the dorsolateral prefrontal cortex (DLPFC), extending findings of previous studies in healthy individuals. Patients with BPD showed significantly longer reaction times (RTs) along with significantly higher activation in the amygdala and insula during emotional distraction compared to healthy participants, suggesting that they were more distracted by emotional pictures during the working memory task. Moreover, in the group of BPD patients, a significant negative correlation was found between activation in limbic brain regions and self-reports of current dissociative states. CONCLUSIONS: Our findings suggest hyper-responsiveness to emotionally distracting pictures in BPD patients that negatively affects working memory performance. This stresses the importance of emotion dysregulation in the context of cognitive functioning. Moreover, our findings suggest that dissociative states have a dampening effect on neural reactivity during emotional challenge in BPD.

Script-driven imagery of self-injurious behavior in patients with borderline personality disorder: a pilot FMRI study.

OBJECTIVE: Self-injurious behavior (SIB) is one of the most distinctive features of borderline personality disorder (BPD) and related to impulsivity and emotional dysregulation. METHOD: Female patients with BPD (n = 11) and healthy controls (n = 10) underwent functional magnetic resonance imaging while listening to a standardized script describing an act of self-injury. Experimental sections of the script were contrasted to the neutral baseline section and group-specific brain activities were compared. RESULTS: While imagining the reactions to a situation triggering SIB, patients with BPD showed significantly less activation in the orbitofrontal cortex compared with controls. Furthermore, only patients with BPD showed increased activity in the dorsolateral prefrontal cortex during this section and a decrease in the mid-cingulate while imagining the self-injurious act itself. CONCLUSION: This pattern of activation preliminary suggests an association with diminished emotion regulation, impulse control as well as with response selection and reappraisal during the imagination of SIB.

A cross-sectional investigation of discontinuation of self-injury and normalizing pain perception in patients with borderline personality disorder.

OBJECTIVE: Several studies have shown reduced pain perception in patients with borderline personality disorder (BPD) and current self-injurious behavior (SIB). The aim of the present study was to test whether pain perception in patients with current SIB is different from that of patients who had stopped SIB, and whether pain perception of the latter group differs from healthy controls (HC). METHOD: We investigated 24 borderline patients and 24 HC. Thirteen patients showed current SIB (BPD-SIB) and 11 patients did not exhibit SIB anymore (BPD-non-SIB). Pain thresholds were assessed using thermal stimuli and laser radiant heat pulses. RESULTS: We found significant linear trends for all pain measures. The BPD-SIB group was less sensitive than the BPD-non-SIB group and the latter were less sensitive than HC. The pain sensitivity negatively correlated with borderline symptom severity. CONCLUSION: The results suggest an association between the termination of SIB, decline of psychopathology and normalization of pain perception in borderline patients.

Oligodipsia and dissociative experiences in borderline personality disorder.

OBJECTIVE: To test the frequency of attenuated fluid intake behavior (oligodipsia) in patients with borderline personality disorder (BPD) and to test if there is an inverse correlation between oligodipsia and the intensity of current dissociative experience in a pilot study. METHOD: Analyses were based on a sample of 15 BPD patients and 15 healthy controls. Fluid intake per diem and intensity of dissociative experience were measured by standardized self-reports daily for 7 days. RESULTS: The BPD patients ingested a significantly lower fluid volume per diem when compared with healthy controls (P < 0.001). We found a strong correlation between intensity of co-occurring dissociative experience and fluid intake or urine osmolality (r = 0.762 and 0.665), independently of sleep quality and general BPD symptom severity. CONCLUSION: The results indicate that oligodipsia may constitute a serious problem at least for a subgroup of BPD patients, and may be correlated with some of the most problematic symptoms of BPD.

Dissociative symptoms are positively related to stress in borderline personality disorder.

OBJECTIVE: According to DSM-IV criteria, dissociative symptoms in borderline personality disorder (BPD) occur in response to stress. Empirical evidence is, however, lacking. METHOD: Using ambulatory monitoring, we assessed dissociative symptoms and subjective ratings of stress every 60 min for 48 h on a palmtop computer in BPD-patients (n = 51), clinical controls (CC; major depression n = 25; panic disorder n = 26), and healthy controls (HC; n = 40). Data analyses were primarily based on hierarchical linear models. RESULTS: In all groups, states of increased stress were paralleled by increased scores of dissociation, thus confirming the hypothesized association between stress and dissociation. The increase in dissociation was more pronounced in BPD-patients when compared with CC and HC. Additionally, BPD-patients reported heightened dissociative experience compared with CC and HC, even after controlling for stress. CONCLUSION: Our data suggest that BPD-patients might be prone to dissociation when experiencing stress and are characterized by a generally heightened level of dissociation.

[Psychopathology and treatment of borderline personality disorder]. / Psychopathologie und Therapie der Borderline-Persönlichkeitsstörung.

Borderline personality disorder (BPD) is a severe psychiatric disorder accounting for about 30% of the total cost for psychiatric inpatient care in the Federal Republic of Germany. Suicidality, self-harm, and severe deterioration of self-esteem lead to chronic suffering for patients and the social environment. With a prevalence rate of 1.5%, BPD is more frequent than schizophrenic disorders. Within the last years, empirically based knowledge concerning the psychopathology, etiopathogenesis, and treatment of BPD have significantly improved. Today most researchers postulate pervasive affective dysregulation at the core of borderline symptomatology and see it as the consequence of an interplay between genetic vulnerability, sociobiographic experience, and dysfunctional behavior. Disorder-specific psychotherapeutic treatments, especially dialectical behavior therapy, show significant improvements in both in- and outpatient settings. Studies on psychopharmacological treatment with promising results have also recently been published. Sufficient outpatient treatment by trained psychotherapists is underdeveloped. Hence, specialized inpatient centers assume this task.

[Treatment of borderline personality disorder with atypical antipsychotic drugs]. / Behandlung der Borderline-Persönlichkeitsstörung mit atypischen Antipsychotika.

Pharmacotherapy of Borderline personality disorder with atypical antipsychotics has recently been the subject of several mostly small studies and case reports. In contrast to the frequent clinical use of this substance class in borderline patients the amount of data on that subject is still sparse. The clinical data gathered thus far suggest a potential use of atypical antipsychotics in the areas of psychotic symptoms, impulsivity and possibly affective symptoms. The drugs were sufficiently well tolerated; however, the observation period in most studies was short and the dosage low. The current set of clinical data does not support the frequently applied polypharmacy. However, recent data suggest that a therapeutic approach combining atypical antipsychotics and psychotherapy may reveal synergistic effects. Future trials should study larger sample sizes over a longer period of time. Open questions are the required dose and the optimal treatment duration.

[Pain processing in patients with borderline personality disorder, fibromyalgia, and post-traumatic stress disorder]. / Schmerzverarbeitung bei Borderline-Persönlichkeitsstörung, Fibromyalgie und Posttraumatischer Belastungsstörung.

The authors review relevant experimental studies on pain perception and processing in psychiatric disorders with traumatic stress as an etiological factor. In borderline personality disorder, post-traumatic stress disorder, and fibromyalgia neurophysiological and neuropsychological patterns of pain processing appear to be different. Experimental studies in borderline patients show a desensitization of pain thresholds whereas patients with fibromyalgia show an opposite pattern, which could be explained by a central augmentation of pain processing. Furthermore, the authors outline methods to assess pain perception (peripheral and central) and describe the neurobiological mechanisms of pain processing, particularly the distinction between the sensory-discriminative lateral system and the affective-motivational medial system. Finally, suggestions for further research and implications for therapy are proposed.

Naloxone in the treatment of acute dissociative states in female patients with borderline personality disorder.

BACKGROUND: Acute dissociative states are common in patients with borderline personality disorder (BPD). However, there are no established pharmacotherapeutic treatment options for this severe clinical condition. METHODS: The effect of 0.4 mg naloxone administered intravenously in acute dissociative states was examined as compared to placebo in a double-blind crossover study in nine patients who met DSM-IV-criteria for BPD. Dissociative symptoms before and 15 min after a single dose of naloxone or saline placebo were assessed using a self-rating instrument for dissociation and aversive inner tension (DSS) and the observer-based items of the Clinician Administered Dissociative States Scale (CADSS). RESULTS: Dissociative symptoms before treatment with naloxone or saline placebo were moderate to severe. After injection of either naloxone or placebo, dissociative symptoms significantly decreased on the DSS (p < 0.01) and the CADSS (p < 0.05). However, there were no significant differences between naloxone and placebo in the reduction of symptoms. Patients who showed the most prominent response to naloxone fulfilled the highest number of DSM-IV-criteria for BPD. CONCLUSIONS: Although it is difficult to draw definite conclusions from this small sample of patients, this study does not support the assumption that naloxone in a single dose of 0.4 mg is superior to placebo in acute dissociative states in patients with BPD. Further studies will investigate whether patients benefit from naloxone in a higher dose or whether subgroups of patients with BPD profit from naloxone in acute dissociative states.

A voxel-based morphometric MRI study in female patients with borderline personality disorder.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Positron emission tomography in female patients with borderline personality disorder.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.