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.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

[Internet-based self-management interventions : Quality criteria for their use in prevention and treatment of mental disorders]. / Internetbasierte Selbstmanagementinterventionen : Qualitätskriterien für ihren Einsatz in Prävention und Behandlung psychischer Störungen.

BACKGROUND: Internet-based self-management interventions are effective in the prevention and treatment of mental disorders; however, for those affected as well as treating clinicians and decision makers in the healthcare sector, it is difficult to identify safe and effective interventions. AIM: Development of quality criteria for self-management interventions. METHODS: Based on a non-specific assessment matrix, a task force from two scientific societies formulated specific quality criteria for self-management interventions for mental disorders. Patients and other relevant stakeholders were involved in the process. RESULTS: A total of 8 key criteria with 17 subordinate points were developed. These must be met for the certification of an intervention. The criteria focus on therapeutic quality requirements, patient safety, data protection and security as well as proof of efficacy in at least one randomized study. A further five criteria are only descriptive and are not required for certification. DISCUSSION: These quality criteria serve as a starting point for the establishment of a certification process. This could help to make internet-based self-management interventions for mental disorders part of routine care in the German healthcare system.

Affective instability across the lifespan in borderline personality disorder - a cross-sectional e-diary study.

OBJECTIVE: Longitudinal and cross-sectional studies suggest that affective instability is inversely related to greater age in borderline personality disorder (BPD). However, existing studies relied on retrospective self-reports of perceived instability. We examined affective instability in everyday life in patients with BPD and healthy controls (HCs) by age in a cross-sectional e-diary study. METHODS: Two hundred and sixty female participants between 14 and 53 years of age (130 patients with BPD and 130 HCs) carried an e-diary over 4 days. The e-diaries emitted a prompting signal in approximately hourly intervals asking participants to rate their current affective state, that is valence (ranging from pleasant to unpleasant) and tense arousal (ranging from calm/relaxed to restless/under tension). RESULTS: Multilevel analyses revealed a significant interaction of age and group predicting affective instability (valence: F(1,255.6)  = 7.59; P < 0.01; tense arousal: F(1,252)  = 6.08; P < 0.01), suggesting that affective instability significantly declines with greater age in patients with BPD. Controlling for the number of comorbid disorders and BPD severity did not change the results, illustrating an inverse relationship between age and affective instability in BPD (significant interaction of age*group for valence: F(1,238.7)  = 5.74; P < 0.02 and tense arousal: F(1,235.2)  = 5.28; P < 0.02). CONCLUSION: Affective instability during daily life declines with greater age in BPD. This decline is irrespective of comorbidity and BPD severity.

A survey on murine gammaherpesvirus 68 in ticks collected in Slovakia.

Murine gammaherpesvirus 68 (MHV-68) is a natural pathogen that infects murid rodents which serve as hosts for Dermacentor reticulatus and Ixodes ricinus ticks. For the first time, MHV-68 was detected in immature I. ricinus ticks feeding on lizards trapped in Slovakia. Later on, MHV-68 infection was detected in D. reticulatus and Haemaphysalis concinna ticks collected on vegetation, which supported the idea that ticks can acquire the virus from feeding on infected hosts. Here, we report MHV-68 infection, which was detected by nested PCR, in D. reticulatus and I. ricinus adult ticks and I. ricinus nymphs collected in five geographically isolated localities, in west, southwest, south and central Slovakia. Viral incidence in ticks was 46.7% (121/259) without considering the season, site of collection and tick species and their life stage. MHV-68 infection was detected in all five localities investigated and in both tick species. Here, for the first time, we report MHV-68 infection in I. ricinus nymphs collected from the vegetation. The finding of virus in ticks from five separated localities suggested that ticks became infected with MHV-68 via feeding on infected rodents; thus, this virus might be a newfound natural pathogen in ticks.

[Internet-based interventions in the treatment of mental disorders : Overview, quality criteria, perspectives]. / Internetbasierte Interventionen in der Behandlung psychischer Störungen : Überblick, Qualitätskriterien, Perspektiven.

BACKGROUND: Mental disorders are frequently not or only insufficiently treated. Internet-based interventions offer the potential of closing the existing gaps in the treatment of mental disorders; however, it is very difficult for patients and providers to choose from the numerous interventions available. OBJECTIVE: The aim of this study was to develop a set of quality criteria that can help patients and care providers to identify recommendable internet-based interventions. METHODS: A selective literature search was carried out and the existing evidence on internet-based interventions in the treatment of mental disorders was collated. A panel of experts then developed quality criteria based on existing models for the systematic assessment of telemedicine applications. RESULTS: Internet-based interventions are effective in the treatment of a broad range of mental disorders. The best evidence is available for depression and anxiety disorders. A set of criteria is proposed for the evaluation of available internet-based interventions using a checklist. These criteria have to be developed further with input from other stakeholders. DISCUSSION: When taking these quality criteria into account, evidence-based interventions available on the internet can make an important contribution to improvement of the care of patients with mental disorders.

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.

Temporal unpredictability of a stimulus sequence and the processing of neutral and emotional stimuli.

Most experimental settings in cognitive neuroscience present a temporally structured stimulus sequence, i.e., stimuli may occur at either constant and predictable or variable and less predictable inter-stimulus intervals (ISIs). This experimental feature has been shown to affect behavior and activation of various cerebral structures such as the parietal cortex and the amygdala. Studies employing explicit or implicit cues to manipulate predictability of events have shown that unpredictability particularly accentuates the response to events of negative valence. The present study investigates whether the effects of unpredictability are similarly affected by the emotional content of stimuli when unpredictability is induced simply by the temporal structure of a stimulus sequence, i.e., by variable as compared to constant ISIs. In an fMRI study, we applied three choice-reaction-time tasks with stimuli of different social-emotional content. Subjects (N=30) were asked to identify the gender in angry and happy faces, or the shape of geometric figures. Tasks were performed with variable and constant ISIs. During the identification of shapes, variable ISIs increased activation in widespread areas comprising the amygdala and fronto-parietal regions. Conversely, variable ISIs during gender identification resulted in a decrease of activation in a small region near the intraparietal sulcus. Our findings reveal that variability in the temporal stimulus structure of an experimental setting affects cerebral activation depending on task demands. They suggest that the processing of emotional stimuli of different valence is not much affected by the decision of employing a constant or a variable temporal stimulus structure, at least in the context of implicit emotion processing tasks. In contrast, temporal structure diversely affects the processing of neutral non-social compared to emotional stimuli, emphasizing the relevance of considering this experimental feature in studies which aim at differentiating social-emotional from cognitive processing in general, and more particularly, aim at identifying circumscribed alterations of social cognition in mental disorders.

[Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager]. / Kardiale und metabolische Risikofaktoren bei schweren psychischen Erkrankungen. Aufgaben eines Präventionsmanagers.

People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

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.

Efficacy of exercise training in SCT patients--who benefits most?

Patients undergoing allo-HCT often experience a substantial loss in physical performance. We have recently published the general effectiveness of an exercise intervention in 105 allo-HCT patients on physical performance and psychosocial well-being. However, predictor variables for differentiated treatment response remained unclear. To determine the impact of basic physical performance on treatment response, we assessed muscle strength and endurance performance at four assessment points before and after allo-HCT. The exercise group started training 2 weeks before admission and ended 6-8 weeks after discharge. Comparing initially fit with unfit classified patients, the fit patients lost 31% of the strength of the knee-extensors, whereas the unfit patients lost only 1% (P<0.05). For endurance capacity, fit patients lost 4% of their walking capability, whereas unfit patients gained 13% (P<0.05). The individual percent change was statistically different at the 0.05 level in all measures of physical performance. Individual training response in allo-HCT patients strongly depends on the initial physical performance level. Unfit patients can be trained safely and may benefit more from this exercise intervention than fit patients. This result is of major clinical relevance and should encourage hematologists to promote exercise even more in impaired/unfit allo-HCT patients.

[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.

[Mindfulness-based psychotherapy]. / Achtsamkeitsbasierte Psychotherapie.

Mindfulness-based psychotherapy is rooted in the Far East meditation culture. In the context of psychotherapy mindfulness-based treatment programs mostly include mindfulness as modular components aiming at acceptance of aversive circumstances or emotions and on improvement of metacognitive awareness. Currently there are five mindfulness-based concepts with different proof of effectiveness: mindfulness-based cognitive therapy (MBCT) can be classified as effective in reducing the risk of relapse in patients with recurrent depression, whereas the popular mindfulness-based stress reduction program (MBSR) reveals only small effect sizes. In summary, mindfulness used as one component in modular conceptualized treatment programs seems to be both acceptable and effective.

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.

[Psychopathology and psychotherapy of borderline personality disorder: state of the art]. / Psychopathologie und Psychotherapie der Borderline-Persönlichkeitsstörung: Zum gegenwärtigen Stand der Forschung.

With a lifetime prevalence of about 3%, borderline personality disorder is a frequent and often debilitating psychiatric disorder, especially during adolescence. Most features of typical borderline pathology can be classified into three dimensions: disturbed affect regulation, identity disturbance and problems in social interaction. Within the last decade several treatment programs have been tailored to the specific needs of borderline therapy and three of them have meanwhile shown empirically proven evidence: dialectical behavior therapy (DBT), mentalization-based therapy (MBT) and schema therapy. Although the studies showed clear superiority of specifically designed treatment programs compared to non-structured standard care, implementation of these programs in the German health care system is far from sufficient. Only one out of every thousand patients suffering from borderline personality disorder receives evidence-based outpatient psychotherapy. This is mirrored by the annual costs for inpatient treatment extending to 4 billion Euros, which is approximately 20% of the total costs for psychiatric care in Germany.