Organization WH. WHO-MSD-MER-2017-depression and other common mental disorders. Global Health Estimates; 2017. pp 1–24.

Charlson FJ, Baxter AJ, Cheng HG, Shidhaye R, Whiteford HA. The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies. Lancet. 2016;388(10042):376–89.

Article  PubMed  Google Scholar 

Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382(9904):1575–86.

Article  PubMed  Google Scholar 

Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996–2013. Psychiatr Serv. 2014;65(8):977–87.

Article  PubMed  Google Scholar 

Rossetto O, Pirazzini M, Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat Rev Microbiol. 2014;12(8):535–49.

Article  CAS  PubMed  Google Scholar 

Dresel C, Bayer F, Castrop F, Rimpau C, Zimmer C, Haslinger B. Botulinum toxin modulates basal ganglia but not deficient somatosensory activation in orofacial dystonia. Mov Disord. 2011;26(8):1496–502.

Article  PubMed  Google Scholar 

Antonucci F, Rossi C, Gianfranceschi L, Rossetto O, Caleo M. Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci. 2008;28(14):3689–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bomba-Warczak E, Vevea JD, Brittain JM, Figueroa-Bernier A, Tepp WH, Johnson EA, et al. Interneuronal transfer and distal action of tetanus toxin and botulinum neurotoxins A and D in central neurons. Cell Rep. 2016;16(7):1974–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caleo M, Spinelli M, Colosimo F, Matak I, Rossetto O, Lackovic Z, et al. Transynaptic action of botulinum neurotoxin type A at central cholinergic boutons. J Neurosci. 2018;38(48):10329–37.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wollmer MA, de Boer C, Kalak N, Beck J, Gotz T, Schmidt T, et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012;46(5):574–81.

Article  PubMed  Google Scholar 

Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. J Psychiatr Res. 2014;52:1–6.

Article  PubMed  Google Scholar 

Magid M, Reichenberg JS, Poth PE, Robertson HT, LaViolette AK, Kruger TH, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(8):837–44.

Article  CAS  PubMed  Google Scholar 

Brin MF, Durgam S, Lum A, James L, Liu J, Thase ME, et al. OnabotulinumtoxinA for the treatment of major depressive disorder: a phase 2 randomized, double-blind, placebo-controlled trial in adult females. Int Clin Psychopharmacol. 2020;35(1):19–28.

Article  PubMed  Google Scholar 

Reichenberg JS, Hauptman AJ, Robertson HT, Finzi E, Kruger TH, Wollmer MA, et al. Botulinum toxin for depression: does patient appearance matter? J Am Acad Dermatol. 2016;74(1):171-3 e1.

Article  PubMed  Google Scholar 

Hess U, Thibault P. Darwin and emotion expression. Am Psychol. 2009;64(2):120–8.

Article  PubMed  Google Scholar 

Gothard KM. The amygdalo-motor pathways and the control of facial expressions. Front Neurosci. 2014;8:43.

Article  PubMed  PubMed Central  Google Scholar 

Li Y, Liu J, Liu X, Su CJ, Zhang QL, Wang ZH, et al. Antidepressant-like action of single facial injection of botulinum neurotoxin A is associated with augmented 5-HT levels and BDNF/ERK/CREB pathways in mouse brain. Neurosci Bull. 2019;35(4):661–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ibragić S, Matak I, Dračić A, Smajlović A, Muminović M, Proft F, et al. Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats. Neurosci Lett. 2016;617:213–7.

Article  PubMed  Google Scholar 

Ni LH, Cao SX, Lian H, Hu XY. Unilateral whisker pad injection of botulinum toxin type a enhances spatial learning in mice. NeuroReport. 2018;29(12):987–92.

Article  CAS  PubMed  Google Scholar 

Soumiya H, Godai A, Araiso H, Mori S, Furukawa S, Fukumitsu H. Neonatal whisker trimming impairs fear/anxiety-related emotional systems of the amygdala and social behaviors in adult mice. PLoS ONE. 2016;11(6): e0158583.

Article  PubMed  PubMed Central  Google Scholar 

Haridas S, Ganapathi R, Kumar M, Manda K. Whisker dependent responsiveness of C57BL/6J mice to different behavioral test paradigms. Behav Brain Res. 2018;336:51–8.

Article  PubMed  Google Scholar 

Tovote P, Esposito MS, Botta P, Chaudun F, Fadok JP, Markovic M, et al. Midbrain circuits for defensive behaviour. Nature. 2016;534(7606):206–12.

Article  CAS  PubMed  Google Scholar 

Hattox AM, Priest CA, Keller A. Functional circuitry involved in the regulation of whisker movements. J Comp Neurol. 2002;442(3):266–76.

Article  PubMed  PubMed Central  Google Scholar 

Takatoh J, Nelson A, Zhou X, Bolton MM, Ehlers MD, Arenkiel BR, et al. New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking. Neuron. 2013;77(2):346–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang J, Gadotti VM, Chen L, Souza IA, Huang S, Wang D, et al. A neuronal circuit for activating descending modulation of neuropathic pain. Nat Neurosci. 2019;22(10):1659–68.

Article  CAS  PubMed  Google Scholar 

Silva C, McNaughton N. Are periaqueductal gray and dorsal raphe the foundation of appetitive and aversive control? A comprehensive review. Prog Neurobiol. 2019;177:33–72.

Article  PubMed  Google Scholar 

Yin W, Mei L, Sun T, Wang Y, Li J, Chen C, et al. A central amygdala-ventrolateral periaqueductal gray matter pathway for pain in a mouse model of depression-like behavior. Anesthesiology. 2020;132(5):1175–96.

Article  CAS  PubMed  Google Scholar 

Li Y, Zeng J, Zhang J, Yue C, Zhong W, Liu Z, et al. Hypothalamic circuits for predation and evasion. Neuron. 2018;97(4):911-24.e5.

Article  CAS  PubMed  Google Scholar 

Bandler R, Shipley MT. Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? Trends Neurosci. 1994;17(9):379–89.

Article  CAS  PubMed  Google Scholar 

Carrive P. The periaqueductal gray and defensive behavior: functional representation and neuronal organization. Behav Brain Res. 1993;58(1–2):27–47.

Article  CAS  PubMed  Google Scholar 

Ko CY, Yang YB, Chou D, Xu JH. The ventrolateral periaqueductal gray contributes to depressive-like behaviors in recovery of inflammatory bowel disease rat model. Front Neurosci. 2020;14:254.

Article  PubMed  PubMed Central  Google Scholar 

Ho YC, Lin TB, Hsieh MC, Lai CY, Chou D, Chau YP, et al. Periaqueductal gray glutamatergic transmission governs chronic stress-induced depression. Neuropsychopharmacology. 2018;43(2):302–12.

Article  CAS  PubMed  Google Scholar 

Qiao H, Li MX, Xu C, Chen HB, An SC, Ma XM. Dendritic spines in depression: what we learned from animal models. Neural Plast. 2016;2016:8056370.

Article  PubMed  PubMed Central  Google Scholar 

Gray JD, Rubin TG, Hunter RG, McEwen BS. Hippocampal gene expression changes underlying stress sensitization and recovery. Mol Psychiatry. 2014;19(11):1171–8.

Article  CAS  PubMed  Google Scholar 

Matthews DW, Deschenes M, Furuta T, Moore JD, Wang F, Karten HJ, et al. Feedback in the brainstem: an excitatory disynaptic pathway for control of whisking. J Comp Neurol. 2015;523(6):921–42.

Article  PubMed  PubMed Central  Google Scholar 

Jensen DB, Klingenberg S, Dimintiyanova KP, Wienecke J, Meehan CF. Intramuscular Botulinum toxin A injections induce central changes to axon initial segments and cholinergic boutons on spinal motoneurones in rats. Sci Rep. 2020;10(1):893.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Faunes M, Onate-Ponce A, Fernandez-Collemann S, Henny P. Excitatory and inhibitory innervation of the mouse orofacial motor nuclei: a stereological study. J Comp Neurol. 2016;524(4):738–58.

Article  CAS  PubMed  Google Scholar