Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial.

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD.Trial registration: drks.de (DRKS00020413) registered 13/01/2020.

Effects of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: results of a randomized, sham-controlled pilot trial.

Dialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in borderline personality disorder (BPD). We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that provides unilateral stimulation to the left dorsolateral prefrontal cortex, would enhance the effects of DBT and reduce BPD-specific symptoms more than sham stimulation. We performed a single-blind, randomized, sham-controlled pilot study to evaluate iTBS as an add-on to 8-week DBT for BPD in routine inpatient treatment. A total of 53 BPD patients were randomly assigned to either iTBS (n = 25) or sham stimulation (n = 28) in weeks 4-8 of DBT; 40 patients were eligible for inclusion in the analyses according to pre-specified criteria (≥ 16 of 20 iTBS sessions). The primary endpoint was change on the 23-item Borderline Symptom List; secondary endpoints were changes in depressive symptoms and general level of functioning. A mixed model repeated measures analysis with a 2 × 2 factorial between-subjects design showed no significant effect of add-on iTBS treatment, but a distinct trend was observed in favor of iTBS (Cohen's d = 0.23 for group difference). We found a main effect of DBT with and without iTBS over time, indicating efficacy of 8 weeks' DBT (d = 0.89-1.12). iTBS may be beneficial as an add-on to DBT in the long term and warrants further evaluation in larger studies. Trial registration Registered at drks.de (no. DRKS00020413) on January 13, 2020.

[Cognitive deficits associated with electroconvulsive therapy for depression: moderating factors and neuropsychological tests]. / Kognitive Defizite der Elektrokonvulsionstherapie bei Depressionen: Moderierende Variablen und neuropsychologische Testverfahren.

Due to the efficacy of electroconvulsive therapy (ECT) in the guideline-based treatment of therapy-resistant depressive episodes and the clinical significance of cognitive impairments, it is necessary to optimize the management of potential side effects. As cognitive side effects of the treatment combined with impairments resulting from the depression may lead to a reduction in the ability to function in social contexts and reduce subjective wellbeing, comprehensive information about and monitoring of potential side effects is essential. In this review we present the clinical relevance and measurement of cognitive side effects that may occur during electroconvulsive therapy. The individual characteristics of the patient as well as the technical and pharmacological parameters that influence the effect of ECT on cognition will be discussed. Furthermore, the recommendations of national and international treatment guidelines for the monitoring of cognitive side effects will be summarized.After ECT, impairments of global cognition, and anterograde as well as retrograde amnesia may occur. While the first two side effects appear to be transient, the extent of retrograde amnesia, particularly for autobiographical information, is not yet well understood and may potentially be present for a longer period. A controversial issue in this context is the question whether there are appropriate instruments for the monitoring of reduction in cognitive performance. In clinical context, a number of different measures are used, and in many cases, monitoring is omitted due to lack of time and methodological uncertainty. Current national and international guidelines make very different suggestions about the monitoring of cognitive side effects during ECT and in German-speaking regions no concrete recommendations are available. In this context, we recommend a revision of current guidelines and identify future areas of research that would further our understanding of the effects of ECT on cognition. These may enable us to keep an eye on these deficiencies better as well as allow us to identify patients that may have a higher risk of developing such impairments.

Comparison of 8-vs-12 weeks, adapted dialectical behavioral therapy (DBT) for borderline personality disorder in routine psychiatric inpatient treatment-A naturalistic study.

Dialectical behavior therapy (DBT) is widely acknowledged as an effective treatment for individuals with borderline personality disorder (BPD). However, the optimal treatment duration within DBT remains a topic of investigation. This retrospective, naturalistic non-randomized study aimed to compare the efficacy of 8 week and 12 week DBT interventions with equivalent content, focusing on the change of BPD-specific symptomatology as the primary outcome and depressive symptoms as the secondary outcome. Overall, 175 patients who participated in DBT and received either 8 week or 12 week intervention were included in the analysis. Routine inpatient treatment was adapted from standard DBT with the modules: skill training, interpersonal skills, dealing with feelings, and mindfulness. Measurements were taken at baseline, mid-point, and endpoint. The borderline symptom list-23 (BSL-23) was used for the assessment of borderline-specific symptoms, while the Beck depression inventory-II (BDI-II) was used for the assessment of depressive symptoms. Statistical analysis was conducted using linear mixed models. Effect sizes were calculated for both measures. The results of the analysis indicated an improvement in both groups over time. Effect sizes were d = 1.29 for BSL-23 and d = 1.79 for BDI-II in the 8 week group, and d = 1.16 for BSL-23 and d = 1.58 for BDI-II in the 12 week group. However, there were no differences in the change of BPD-specific symptoms or the severity of depressive symptoms between the 8 week and 12 week treatment duration groups. Based on these findings, shorter treatment durations, like 8 weeks, could be a viable alternative, offering comparable therapeutic benefits, potential cost reduction, and improved accessibility. However, further research is needed to explore factors influencing treatment outcomes and evaluate the long-term effects of different treatment durations in DBT for BPD.Trial registration: drks.de (DRKS00030939) registered 19/12/2022.

Longitudinal progression of posterior cortical atrophy over 11 years: Relationship between lesion topology and clinical deficits.

Posterior cortical atrophy (PCA) is a rare form of dementia primarily characterized by slowly progressing deterioration of visual processing corresponding to atrophy in the posterior parietal and occipital cortices with less prominent memory loss than are usually seen in other forms of dementia such as Alzheimer's Disease (AD). In the present case report, we describe longitudinal data over a period of 11 years regarding clinical and neuropsychological impairments and their relation to the location and extent of cortical changes related to higher order visual processing in a patient with posterior cortical atrophy. In our patient, visual processing deficits concerning space, motion and object perception emerged at the age of 50 and continued to worsen. By the age of 58, while the perception of contrast, color and figure-ground separation appeared undisturbed the patient exhibited pronounced dorsal- and ventral-related visual deficits, which continued to worsen with age. The patient's MRI scans over the course of the disease revealed increasing circumscribed and bilateral atrophy of the parietal and occipital cortices, with a right-sided predominance. The specific localization of cortical atrophy, the slow progression characterized by visual processing deficits and relatively preserved memory were the main criteria for the diagnosis of posterior cortical atrophy. The case report also highlights the importance of an early extensive neurological and neuropsychological evaluation of visual deficits that occur without the presence of ophthalmological disease.

Combined Effects of Glucocorticoid and Noradrenergic Activity on Loss Aversion.

Loss aversion is a well-known behavioral regularity in financial decision making, describing humans' tendency to overweigh losses compared to gains of the same amount. Recent research indicates that stress and associated hormonal changes affect loss aversion, yet the underlying neuroendocrine mechanisms are still poorly understood. Here, we investigated the causal influence of two major stress neuromodulators, cortisol and noradrenaline, on loss aversion during financial decision making. In a double-blind, placebo-controlled between-subject design, we orally administered either the α2-adrenergic antagonist yohimbine (increasing noradrenergic stimulation), hydrocortisone, both substances, or a placebo to healthy young men. We tested the treatments' influence on a financial decision-making task measuring loss aversion and risk attitude. We found that both drugs combined, relative to either drug by itself, reduced loss aversion in the absence of an effect on risk attitude or choice consistency. Our data suggest that concurrent glucocorticoid and noradrenergic activity prompts an alignment of reward- with loss-sensitivity, and thus diminishes loss aversion. Our results have implications for the understanding of the susceptibility to biases in decision making.

Dissociable roles of glucocorticoid and noradrenergic activation on social discounting.

People often exhibit prosocial tendencies towards close kin and friends, but generosity decreases as a function of increasing social distance between donor and recipient, a phenomenon called social discounting. Evidence suggests that acute stress affects prosocial behaviour in general and social discounting in particular. We tested the causal role of the important stress neuromodulators cortisol (CORT) and noradrenaline (NA) in this effect by considering two competing hypotheses. On the one hand, it is possible that CORT and NA act in concert to increase generosity towards socially close others by reducing the aversiveness of the cost component in costly altruism and enhancing the emotional salience of vicarious reward. Alternatively, it is equally plausible that CORT and NA exert dissociable, opposing effects on prosocial behaviour based on prior findings implicating CORT in social affiliation, and NA in aggressive and antagonistic tendencies. We pharmacologically manipulated CORT and NA levels in a sample of men (N = 150) and found that isolated hydrocortisone administration promoted prosocial tendencies towards close others, reflected in an altered social discount function, but this effect was offset by concurrent noradrenergic activation brought about by simultaneous yohimbine administration. These results provide inceptive evidence for causal, opposing roles of these two important stress neuromodulators on prosocial behaviour, and give rise to the possibility that, depending on the neuroendocrine response profile, stress neuromodulator action can foster both tend-and-befriend and fight-or-flight tendencies at the same time.

Gender-Specific Effects of Cognitive Load on Social Discounting.

We live busy, social lives, and meeting the challenges of our complex environments puts strain on our cognitive systems. However, cognitive resources are limited. It is unclear how cognitive load affects social decision making. Previous findings on the effects of cognitive load on other-regarding preferences have been ambiguous, allowing no coherent opinion whether cognitive load increases, decreases or does not affect prosocial considerations. Here, we suggest that social distance between individuals modulates whether generosity towards a recipient increases or decreases under cognitive load conditions. Participants played a financial social discounting task with several recipients at variable social distance levels. In this task, they could choose between generous alternatives, yielding medium financial rewards for the participant and recipient at variable social distances, or between a selfish alternative, yielding larger rewards for the participant alone. We show that the social discount function of male participants was significantly flattened under high cognitive load conditions, suggesting they distinguished less between socially close and socially distant recipients. Unexpectedly, the cognitive-load effect on social discounting was gender-specific: while social discounting was strongly dependent on cognitive load in men, women were nearly unaffected by cognitive load manipulations. We suggest that cognitive load leads men, but not women to simplify the decision problem by neglecting the social distance information. We consider our study a good starting point for further experiments exploring the role of gender in prosocial choice.

Exogenous cortisol causes a shift from deliberative to intuitive thinking.

People often rely on intuitive judgments at the expense of deliberate reasoning, but what determines the dominance of intuition over deliberation is not well understood. Here, we employed a psychopharmacological approach to unravel the role of two major endocrine stress mediators, cortisol and noradrenaline, in cognitive reasoning. Healthy participants received placebo, cortisol (hydrocortisone) and/or yohimbine, a drug that increases noradrenergic stimulation, before performing the cognitive reflection test (CRT). We found that cortisol impaired performance in the CRT by biasing responses toward intuitive, but incorrect answers. Elevated stimulation of the noradrenergic system, however, had no effect. We interpret our results in the context of the dual systems theory of judgment and decision making. We propose that cortisol causes a shift from deliberate, reflective cognition toward automatic, reflexive information processing.