Effects of glabellar botulinum toxin injections on resting-state functional connectivity in borderline personality disorder.

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect.

Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: A randomized controlled trial.

BACKGROUND: Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders. AIM: This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD). METHODS: Fifty-four patients with BPD were randomly assigned to treatment with BTX (n = 27) or a minimal acupuncture (ACU) control condition (n = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression. RESULTS: Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: M = -0.39, SD = 0.39; ACU: M = -0.35, SD = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found-F(1,5323) = 0.017, p = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness. CONCLUSION: Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research.ClinicalTrials.gov registry: Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.

Postmarketing safety surveillance data reveals protective effects of botulinum toxin injections against incident anxiety.

Randomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated with reduced incidence rates of depression across various non-psychiatric indications, which confirms the previous findings independently of specific expectations to an antidepressant effect of BoNT. The rationale of using BoNT to treat depression is to interrupt proprioceptive body feedback that may reinforce negative emotions. Negative emotions also occur in other mental disorders, suggesting a transdiagnostic therapeutic potential of BoNT in psychiatry. Here we report an analysis of the FAERS database, in which we found that, compared to alternative treatments, BoNT injections were associated with lower incidence of anxiety symptoms and related disorders. Among seven indications/injection sites, we found this protective effect of BoNT in cosmetic use/facial muscles, migraine/facial and head muscles, spasms and spasticity/upper and lower limbs, torticollis and neck pain/neck muscles, and sialorrhea/parotid and submandibular glands (reporting odds ratios 0.79-0.27). These findings are encouraging for possible future RCTs on the use of BoNT as a treatment for anxiety and related disorders.

Botulinum toxin for the management of depression: An updated review of the evidence and meta-analysis.

Botulinum toxin (BTX) treatment of glabellar frown lines is one of the most common procedures in aesthetic medicine. In addition to its cosmetic effect, the neurotoxin has been shown to have a positive influence on mood and affect. Several randomized clinical trials (RCTs) have examined the effect of botulinum toxin on the treatment of depression. Combining the results of the five RCTs in a random effects meta-analysis revealed that patients treated with BTX showed a more intense improvement of depressive symptoms in comparison to subjects that received placebo injections (d = 0.98). Despite methodological limitations, the results of this study emphasize the effectiveness of BTX in the treatment of depression and therefore pave the way for its use in the field of psychiatry.

The Use of Botulinum Toxin for Treatment of Depression.

A series of clinical studies have shown that botulinum toxin can treat major depression. Subjects suffering from unipolar depression may experience a quick, strong, and sustained improvement in the symptoms of depression after a single glabellar treatment with botulinum toxin.Preliminary data suggest that botulinum toxin therapy may also be effective in the treatment of other mental disorders characterized by an excess of negative emotions, such as borderline personality disorder.The mood-lifting effect of botulinum toxin therapy is probably mediated by the interruption of a proprioceptive feedback loop from the facial musculature to the emotional brain.

[Memory clinics in Germany-structural requirements and areas of responsibility]. / Gedächtnisambulanzen in Deutschland ­ strukturell-organisatorische Voraussetzungen und Aufgabenfelder.

BACKGROUND: Memory clinics (MC) are institutions specialized in the (differential) diagnostics, treatment, education, management and counseling of diseases related to dementia and their risk stages. In Germany, they have a variety of different organizational forms. Due to the growing diagnostic options in neurodegenerative diseases, the increasing demand for early detection and prediction as well as foreseeable new diagnostic procedures and disease-modifying treatment, it is important to standardize the structural prerequisites and areas of responsibility of MC. OBJECTIVE: The article proposes structural and organizational requirements and procedures and a harmonized mode of operation for MC in Germany. METHOD: Expert consensus of psychiatrists, neurologists and geriatricians from academic and nonacademic institutions. RESULTS: The MC should provide the specialist standards of psychiatry and/or neurology. They need to implement the recommendations of the national guidelines on dementia (S3LL) with respect to the (differential) diagnostics and treatment of dementia. With respect to the early detection and prediction of neurodegenerative disorders, they extend beyond the current German guideline standards. In MC, mild cognitive impairment (MCI) is understood as an at-risk or prodromal stage of diseases related to dementia and biomarkers are consistently applied for etiological (early and differential) diagnostics. There is a requirement for close interaction with specialized diagnostic disciplines. Furthermore, MC should also offer comprehensive advice on social and legal issues and provide caregiver support. They should integrate current knowledge from research into care and serve as regional expert centers. CONCLUSION: The MC should implement evidence-based standards in diagnostics and treatment and introduce innovations in the care of patients with cognitive disorders and at-risk and prodromal stages. Their role in the German healthcare system must be strengthened. Sufficient and sustained funding needs to be established, since current reimbursement does not cover costs.

Shrink that frown! Botulinum toxin therapy is lifting the face of psychiatry.

Treating glabellar frown lines with injections of botulinum toxin is the most frequently applied procedure in aesthetic medicine. In addition to its cosmetic effect, botulinum toxin may also positively modulate mood and affect, which may contribute to its popularity. A series of clinical studies has shown that this modulation can be used in the treatment of major depression. After a single glabellar treatment with botulinum toxin, patients suffering from unipolar depression experienced a quick, strong and sustained improvement in the symptoms of depression. Preliminary data suggest that botulinum toxin therapy may also be effective in the treatment of other mental disorders characterized by an excess of negative emotions, such as borderline personality disorder. Thus, the extreme bottom-up approach of paralyzing the facial muscles to influence the emotional brain via proprioceptive feedback mechanisms may represent a paradigm shift in psychiatric therapy.

Botulinum Toxin as a Treatment for Depression in a Real-world Setting.

OBJECTIVES: A series of randomized controlled trials have shown the efficacy of glabellar botulinum toxin (BTX) injection as a treatment for depression in women. We wanted to extend these findings and assess how they may be translated to a real-world setting. METHODS: For that purpose, 42 patients with severe, in most cases chronic and treatment-resistant depression received adjunctive treatment with BTX in private practice. Depression severity was rated before and 3 weeks after the treatment using the Hamilton Depression Rating Scale, the Montgomery Åsberg Depression Rating Scale, and the Beck Depression Inventory. RESULTS: Almost all of the patients improved clinically, with depression scores dropping by 27% on all 3 scales in the sample as a whole. These changes were highly significant (P<0.001, paired t test or Wilcoxon test) and the absolute prepost score differences were similar to those observed in previous randomized controlled trials. Importantly, treatment effects did not differ between male (n=23) and female (n=19) patients. CONCLUSIONS: These findings suggest that glabellar BTX injection may also be effective in the treatment of severe depression and in the treatment of depression in men, when treatment is carried out not just in clinical trials but in real-world settings.

Interaction between behavioral inhibition and emotional processing in borderline personality disorder using a pictorial emotional go/no-go paradigm.

Borderline personality disorder (BPD) is characterized by difficulties in emotional regulation and impulse control. In this study, we presented a novel picture-based emotional go/no-go task with distracting emotional faces in the background, which was administered to 16 patients with BPD and 16 age-matched healthy controls. The faces displayed different emotional content (angry, neutral, or happy). Results showed differences in sensitivity between patients and the control group, with patients exhibiting less sensitivity in the task, and also showed influences of emotional content represented in the distracting faces in both groups. Specifically, happy faces decreased sensitivity compared to angry faces. It seemed as though processing of a positive emotional stimulus led to a more relaxed state and thereby to decreased sensitivity, while a negative emotional stimulus induced more alertness and tension, leading to higher sensitivity. Thus, this paradigm is suitable to investigate the interplay between emotion processing and impulse control in patients with BPD.

The New Hamburg-Hannover Agitation Scale in Clinical Samples: Manifestation and Differences of Agitation in Depression, Anxiety, and Borderline Personality Disorder.

BACKGROUND/AIMS: Agitation is a burdening phenomenon that occurs in a variety of psychiatric disorders. The aim of this study was to give a first direction for agitation occurrence in depression, anxiety disorder, and borderline personality disorder (BPD) as well as in healthy controls with and without psychiatric record. METHODS: Using the Hamburg-Hannover Agitation Scale (H2A), an instrument that allows for the measurement of agitation independently of the presence of a specific disorder, a patient sample (n = 158) and a healthy control group (n = 685) with (n = 94) and without (n = 591) psychiatric record were examined. The data were mainly analysed using ANOVAs and post hoc tests. RESULTS: Patients showed significantly higher H2A agitation levels than healthy controls. Within the clinical sample, BPD patients exhibited the strongest manifestation of agitation, scoring significantly higher than the depression and the anxiety disorder sample, while these two subgroups did not significantly differ from each other. Moreover, healthy subjects with a psychiatric record experienced a significantly stronger agitation than subjects without a psychiatric record. CONCLUSION: Further studies are needed with larger, more balanced, and differentiated sample sizes including a wider range of clinical pictures. The results demonstrate that agitation occurs and differs in psychiatric patients as well as in healthy controls.

Depression--An emerging indication for botulinum toxin treatment.

The treatment of glabellar frown lines with botulinum toxin injection is one of the most prevalent procedures in esthetic medicine. It is possible that the popularity of this intervention is not only owing to its cosmetic effect but also to modulatory effects on mood and affectivity. Recently, a series of studies including three randomized controlled trials have consistently shown that such effects can be used in the treatment of depression. Predominantly female patients suffering from partly chronic and treatment resistant unipolar depression experienced a quick, strong and sustained improvement in depressive symptoms after a single glabellar treatment with botulinum toxin A as a sole or adjunctive therapy. If these findings are further corroborated in additional studies, the ever-growing spectrum of applications for botulinum toxin may spread into the field of psychiatry, showing that the superficial paralysis of facial muscles may, probably via proprioceptive feedback mechanisms, have profound effects on the emotional brain.

The Hamburg-Hannover Agitation Scale (H2A): Development and validation of a self-assessment tool for symptoms of agitation.

BACKGROUND: Agitation has long been underestimated as a symptom occurring across psychiatric disorders. While several instruments exist for highly specific clinical target groups (e.g., dementia, traumatic brain injury), no tool captures agitation in a broader range of psychiatric patients. The Hamburg-Hannover Agitation Scale (H2A) has been designed to satisfy this demand. This study concentrated on the development and validation of the scale in a psychiatric and a healthy control sample. METHODS: The H2A was developed, tested in an expert sample, and revised. The German version was validated in a study involving two clinical institutions. Patients (n = 180) completed the H2A and several other questionnaires in order to test for congruent and discriminant validity. Healthy subjects (n = 685) completed the H2A only. The H2A was translated into English. RESULTS: The H2A showed very satisfying quality criteria (reliability, selectivity, item difficulty) and regression analysis demonstrated the H2A's ability to distinguish between subjects with a psychiatric diagnosis and healthy subjects with or without psychiatric record. Factor analysis revealed a three-factorial structure representing a physiological/somatic, a mental and a mixed ('psychophysiological') dimension of agitation. LIMITATIONS: Although validation showed promising quality criteria and predictive value of the H2A, calibration tests with bigger and more balanced sample sizes are necessary. CONCLUSIONS: Agitation has become more clinically relevant as a symptom occurring in various affective disorders, yet its assessment is limited. The H2A was developed in order to meet this need. Validation of the H2A revealed very satisfactory item and scale quality criteria promoting its utility.

Association between subjective actual sleep duration, subjective sleep need, age, body mass index, and gender in a large sample of young adults.

BACKGROUND: Poor sleep is a major health concern, and there is evidence that young adults are at increased risk of suffering from poor sleep. There is also evidence that sleep duration can vary as a function of gender and body mass index (BMI). We sought to replicate these findings in a large sample of young adults, and also tested the hypothesis that a smaller gap between subjective sleep duration and subjective sleep need is associated with a greater feeling of being restored. METHODS: A total of 2,929 university students (mean age 23.24±3.13 years, 69.1% female) took part in an Internet-based survey. They answered questions related to demographics and subjective sleep patterns. RESULTS: We found no gender differences in subjective sleep duration, subjective sleep need, BMI, age, or feeling of being restored. Nonlinear associations were observed between subjective sleep duration, BMI, and feeling of being restored. Moreover, a larger discrepancy between subjective actual sleep duration and subjective sleep need was associated with a lower feeling of being restored. CONCLUSION: The present pattern of results from a large sample of young adults suggests that males and females do not differ with respect to subjective sleep duration, BMI, or feeling of being restored. Moreover, nonlinear correlations seemed to provide a more accurate reflection of the relationship between subjective sleep and demographic variables.

Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine whether a single treatment of botulinum toxin A in the forehead (glabellar) region can improve symptoms of depression in patients with major depressive disorder (MDD), as defined by DSM-IV criteria. METHOD: Thirty participants were randomly assigned to receive either placebo or botulinum toxin A (BTA; onabotulinumtoxinA) injections in the forehead. Female participants received 29 units; male participants received 39 units. At week 12, the groups were crossed over. Participants were evaluated at weeks 0, 3, 6, 12, 15, 18, and 24 for improvement in MDD symptoms using the Patient Health Care Questionnaire-9, Beck Depression Inventory (BDI), and 21-Item Hamilton Depression Rating Scale (HDRS-21) objective measurement scales. The primary outcome was the rate of HDRS-21 response, defined as ≥ 50% score reduction from baseline. The study occurred from July 2011 to November 2012. RESULTS: Patients who received BTA at week 0 (BTA-first group) and at week 12 (BTA-second group) had a statistically significant reduction in MDD symptoms as compared to placebo. Improvement in MDD continued over 24 weeks in the group that received BTA first even though the cosmetic effects of BTA wore off at 12 to 16 weeks. HDRS-21 response rates were 55% (6/11) in the BTA-first group, 24% (4/17) in the BTA-second group, and 0% (0/19) in the placebo group (P < .0001). HDRS-21 remission rates (score ≤ 7) were 18% (2/11), 18% (3/17), and 0% (0/19), respectively (P = .057). HDRS-21 scores dropped -46% and -35% in the BTA-first and -second groups versus -2% in the placebo group (P < .0001). The BDI response rate (≥ 50% reduction from baseline) was 45% (5/11) in the BTA-first group, 33% (6/18) in the BTA-second group, and 5% (1/19) in the placebo group (P = .0067). BDI remission rates (score ≤ 9) were 27% (3/11), 33% (6/18), and 5% (1/19), respectively (P = .09). BDI scores dropped -42% and -35% in the BTA-first and -second groups versus -15% in the placebo group (P < .0001). CONCLUSIONS: Botulinum toxin A injection in the glabellar region was associated with significant improvement in depressive symptoms and may be a safe and sustainable intervention in the treatment of MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01392963.

Agitation predicts response of depression to botulinum toxin treatment in a randomized controlled trial.

In a randomized, controlled trial (n = 30), we showed that botulinum toxin injection to the glabellar region produces a marked improvement in the symptoms of major depression. We hypothesized that the mood-lifting effect was mediated by facial feedback mechanisms. Here we assessed if agitation, which may be associated with increased dynamic psychomotor activity of the facial musculature, can predict response to the treatment. To test this hypothesis, we re-analyzed the data of the scales from our previous study on a single item basis and compared the baseline scores in the agitation item (item 9) of the Hamilton Depression Rating Scale (HAM-D) between responders (n = 9) and participants who did not attain response (n = 6) among the recipients of onabotulinumtoxinA (n = 15). Responders had significantly higher item 9 scores at baseline [1.56 + 0.88 vs. 0.33 + 0.52, t (13) = 3.04, d = 1.7, p = 0.01], while no other single item of the HAM-D or the Beck Depression Inventory was associated with treatment response. The agitation score had an overall precision of 78% in predicting response in a receiver operating characteristic (ROC) analysis (area under the curve, AUC = 0.87). These data provide a link between response to botulinum toxin treatment with a psychomotor manifestation of depression and thereby indirect support of the proposed facial feedback mechanism of action. Moreover, it suggests that patients with agitated depression may particularly benefit from botulinum toxin treatment.