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

Abstract

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.

Modulation of amygdala activity for emotional faces due to botulinum toxin type A injections that prevent frowning

“…In addition to the well-established modulation of amygdala activity by emotion, we found evidence consistent with that of prior studies by Kim and colleagues 21 , Hennenlotter and colleagues 20 , and Kruger and colleagues 52 , in that the amygdala’s responsiveness to emotion can be modulated by local facial chemodenervation. We do acknowledge differences in direction of effects but note differences in the contrasts and baselines across experiments.…”

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape

“…Supplementary Tables S1–S3 present the outcomes of the quality assessment for the included studies. Eleven out of seventeen studies (64.7%) were randomized [ 15 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], whereas the other six non-randomized studies presented five case series (29.4%) [ 16 , 34 , 35 , 36 , 37 ] and one open-label trial (5.9%) [ 38 ]. Among the case series, the condition was measured in a standard and reliable way, the outcomes were clearly reported, and four out of five (80.0%) case series had clear and appropriate statistical analyses.…”

“…In terms of masking, seven of the studies (41.2%) were double-blind, seven studies (41.2%) were open-label trials, two were single-blind (11.8%), and the remaining one (5.9%) had unknown masking ( Figure 3 A). Ten studies (58.8%) used parallel assignment [ 13 , 14 , 15 , 17 , 18 ], five (29.4%) used single-group assignment, one study used crossover assignment (5.9%), and the remaining study (5.9%) had concealed assignment ( Figure 3 B).…”

“…Eight (47.0%) of the studies defined secondary outcomes as well. These included the BDI (five studies, 29.4%) [ 14 , 15 , 16 ], Hamburg–Hannover Agitation Scale (one study, 5.9%), and HAM-D (two studies, 11.8%). Electrophysiology methods, laboratory tests, and assessment of biological rhythms were not employed in any of the trials.…”

“…Several studies have examined the association between BONT-A injections and emotional processing, suggesting that BONT-A may be used as a potential treatment for affective disorders [ 10 , 11 , 12 ]. Putative neurobiological markers of treatment response to BONT-A have also been explored, with functional magnetic resonance imaging (fMRI) studies [ 13 , 14 , 15 ] providing evidence of successful attenuation of amygdala reactivity in response to angry faces upon paralysis of the facial muscles via BONT-A injection.…”