Treatment of Borderline Personality Disorder with Botulinumtoxin A: Neuronal Foundations of Emotion Processing and Impulse Control (BTX-BPS)

• Applicant: Professor Dr. Tillmann Krüger
• Subject Area: Biological Psychiatry
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398977992

Clinical trials have shown that a single injection with botulinum toxin A of the glabella region can lead to a rapid and long lasting alleviation of depressive symptoms (Wollmer et al. 2012, Finzi & Rosenthal 2014, Magid et al. 2014). Most probably botulinum toxin A does not exert specific antidepressant effects but leads to a general attenuation of negative emotions such as anxiety and sadness through interruption of a facial feedback: By paralysing muscles that express negative emotions (mm. corrugatores supercilii and m. procerus) proprioceptive signals to the brain, normally responsible for maintenance and enhancement of these emotions, are diminished (Facial Feedback Theory). In particular, Borderline Personality Disorders (BPD) seem appropriate for such an approach as they show an excess of negative emotions (anxiety, sadness, anger, disgust), and most of functional imaging studies show an increased activation of the amygdala in these patients. The entire study consists of two parts: (1) A clinical randomised controlled trial (according to German Medicine Law, AMG) which already received non-industrial funding (Asklepios proresearch) and approval of the local ethics committee and regulatory authorities (NCT02728778). The clinical trial aims at investigating the efficacy and safety of a single treatment of the glabella region with botulinum toxin A in female patients with BPD compared to a minimal acupuncture treatment of head and face (n=54). (2) An experimental study aiming at identifying the neuronal underpinnings of such a treatment in patients with BPD. The application refers only to this second part of the entire study Purpose of the experimental study is the identification of neuronal mechanisms of botulinum toxin A injections using the following approach: (1) classification/processing of emotional faces of different valence; (2) completion of an inhibitory task (emotional GoNoG paradigm) incorporating the interference of emotion and inhibition; and (3) resting state activity of the brain/brainstem in patients with BPD using functional magnet resonance imaging (fMRI). We hypothesize that the treatment of the glabella region with botulinum toxin A leads to less negative ratings of neutral or ambiguous facial expressions and an improved inhibitory performance using the GoNogo paradigm (behavioral level). On the neuronal levels we expect a diminished activation of the amygdala and associated brain areas during processing of negative emotional faces, an altered connectivity within the default mode network through attenuation of somatosensory input and a decreased activity of emotion related brain regions as well as increased activity of prefrontal inhibitory brain regions during the GoNogo paradigm.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Florian Beissner; Privatdozent Dr. M. Axel Wollmer