M. Axel Wollmer

Facing depression with botulinum toxin: A randomized controlled trial

Positive effects on mood have been observed in subjects who underwent treatment of glabellar frown lines with botulinum toxin and, in an open case series, depression remitted or improved after such treatment. Using a randomized double-blind placebo-controlled trial design we assessed botulinum toxin injection to the glabellar region as an adjunctive treatment of major depression. Thirty patients were randomly assigned to a verum (onabotulinumtoxinA, n = 15) or placebo (saline, n = 15) group. The primary end point was change in the 17-item version of the Hamilton Depression Rating Scale six weeks after treatment compared to baseline. The verum and the placebo groups did not differ significantly in any of the collected baseline characteristics. Throughout the sixteen-week follow-up period there was a significant improvement in depressive symptoms in the verum group compared to the placebo group as measured by the Hamilton Depression Rating Scale (F((6,168)) = 5.76, p < 0.001, η(2) = 0.17). Six weeks after a single treatment scores of onabotulinumtoxinA recipients were reduced on average by 47.1% and by 9.2% in placebo-treated participants (F((1,28)) = 12.30, p = 0.002, η(2) = 0.31, d = 1.28). The effect size was even larger at the end of the study (d = 1.80). Treatment-dependent clinical improvement was also reflected in the Beck Depression Inventory, and in the Clinical Global Impressions Scale. This study shows that a single treatment of the glabellar region with botulinum toxin may shortly accomplish a strong and sustained alleviation of depression in patients, who did not improve sufficiently on previous medication. It supports the concept, that the facial musculature not only expresses, but also regulates mood states.

Cholesterol-related genes in Alzheimer's disease.

Experimental data show that cholesterol can modulate central processes in the pathogenesis of Alzheimers disease (AD). The epidemiological link between elevated plasma cholesterol at midlife and increased risk for AD and the possibility that 3-hydroxy-3-methylglutaryl-coenzym A reductase inhibitors (statins) may be protective against AD support a role of cholesterol metabolism in AD and have rendered it a potential therapeutic target in the treatment and prevention of the disease. The strong association of AD and AD endophenotypes with the APOE gene provides a genetic link between AD and cholesterol metabolism, because the apolipoprotein E (ApoE) is the most prevalent cholesterol transport protein in the central nervous system. Against this background several other genes with a role in cholesterol metabolism have been investigated for association with AD. In this review a compilation of genes related to cholesterol based on the information of the AmiGo gene ontology database is matched with the AlzGene database of AD candidate genes. 56 out of 149 (37.6%) genes with a relation to cholesterol metabolism have been investigated for association with AD. Given that only 660 out of about 23,000 (2.9%) genes have been assessed in hypothesis-driven candidate gene studies on AD, the cholesterol metabolic pathway is strongly represented among these genes. Among 34 cholesterol-related genes for which association with AD has been described APOE, CH25H, CLU, LDLR, SORL1 outstand with positive meta-analyses. However, it is unclear, if their association with AD is mediated by cholesterol-related mechanisms or by more specific direct effects of the respective proteins on Abeta metabolism.

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.

Vestibular Stimulation on a Motion-Simulator Impacts on Mood States

We are familiar with both pleasant and unpleasant psychotropic effects of movements associated with vestibular stimulation. However, there has been no attempt to scientifically explore the impact of different kinds of vestibular stimulation on mood states and biomarkers. A sample of 23 healthy volunteers were subjected to a random sequence of three different passive rotational (yaw, pitch, roll) and translational (heave, sway, surge) vestibular stimulation paradigms using a motion-simulator (hexapod). Mood states were measured by means of questionnaires and visual analog scales. In addition, saliva cortisol and α-amylase samples were taken. Compared to a subliminal control paradigm all rotational and two translational stimulations produced significant changes in mood states: Yaw rotation was associated with feeling more comfortable, pitch rotation with feeling more alert and energetic, and roll rotation with feeling less comfortable. Heave translation was associated with feeling more alert, less relaxed, and less comfortable and surge translation with feeling more alert. Biomarkers were not affected. In conclusion, we provide first experimental evidence that passive rotational and translational movements may influence mood states on a short-term basis and that the quality of these psychotropic effects may depend on the plane and axis of the respective movements.

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.

Cox’s Chair Revisited: Can Spinning Alter Mood States?

Although there is clinical and historical evidence for a vivid relation between the vestibular and emotional systems, the neuroscientific underpinnings are poorly understood. The “spin doctors” of the nineteenth century used spinning chairs (e.g., Cox’s chair) to treat conditions of mania or elevated arousal. On the basis of a recent study on a hexapod motion-simulator, in this prototypic investigation we explore the impact of yaw stimulation on a spinning chair on mood states. Using a controlled experimental stimulation paradigm on a unique 3-D-turntable at the University of Zurich we included 11 healthy subjects and assessed parameters of mood states and autonomic nervous system activity. The Multidimensional Mood State Questionnaire and Visual Analog Scales (VAS) were used to assess changes of mood in response to a 100 s yaw stimulation. In addition heart rate was continuously monitored during the experiment. Subjects indicated feeling less “good,” “relaxed,” “comfortable,” and “calm” and reported an increased alertness after vestibular stimulation. However, there were no objective adverse effects of the stimulation. Accordingly, heart rate did not significantly differ in response to the stimulation. This is the first study in a highly controlled setting using the historical approach of stimulating the vestibular system to impact mood states. It demonstrates a specific interaction between the vestibular system and mood states and thereby supports recent experimental findings with a different stimulation technique. These results may inspire future research on the clinical potential of this method.

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.

Ein neuer Wirkstoff gegen Depressionen?: Botulinumtoxin

Der Ausdruck negativer Emotionen wird über propriozeptive Afferenzen der Gesichtsmuskulatur dem ZNS zurückgemeldet und kann darüber möglicherweise eine Depression aufrechterhalten und verstärken. Die Unterbrechung dieser Facial-Feedback-Schleife durch gezielte Hemmung mimischer Muskel in der Glabellaregion mithilfe von Botulinumtoxin-Injektionen ist ein neuer Ansatz in der Behandlung der Depression.

Contents Vol. 49, 2016

Founded 1897 as ‘Monatsschrift für Psychiatrie und Neurologie’, continued 1957–1967 as ‘Psychiatria et Neurologia’, continued 1968–1983 as ‘Psychiatria Clinica’ Founders: C. Wernicke and Th. Ziehen Successors: K. Bonhoeffer (1912–1938), J. Klaesi (1939–1967), E. Grünthal (1953–1973), N. Petrilowitsch (1968–1970), Th. Spoerri (1971–1973), P. Berner (1974–1999), E. Gabriel (1974–2004), Ch. Mundt (2000–2011)