Neurobiological basis of chiropractic manipulative treatment of the spine in the care of major depression

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Aysha Karim Kiani
Paolo Enrico Maltese
Astrit Dautaj
Stefano Paolacci
Danjela Kurti
Pietro Maria Picotti
Matteo Bertelli


Chiropractic, depression, neurtrophin


Background and aim: Major depressive disorder is associated with an autonomic nervous system imbalance. All the symptoms of depression (high cortisol, high adrenalin, insomnia, agitation, anxiety) can probably be attributed to over-activation of the sympathetic nervous system. We performed this review in order to highlight the possible links between chiropractic intervention, its potential molecular effects and its possible outcomes on patients with depression. Methods: We performed a literature search for all the relevant manuscript regarding the effects of chiropractic and depression on the autonomic nervous system. Results: Chiropractic care and spinal manipulation regulate the autonomic nervous system at peripheral level and its projections to the central nervous system. In particular, they may activate the parasympathetic system to counterbalance the activity of the sympathetic system. Vagal parasympathetic stimulation is also considered an effective therapy for major depression as it releases neurotrophins essential for anti-depressive therapies, including brain-derived neurotrophic factor and nerve growth factor. Conclusion: Chiropractic and spinal manipulative therapies along with vagal nerve stimulation may therefore be regarded as treatment options for depression.


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[1] Gold PW, Machado-Vieira R, Pavlatou MG. Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast 2015; 2015: 581976.
[2] Jochum T, Hoyme J, Schulz S, Weißenfels M, Voss A, Bär K-J. Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal. Drug Alcohol Depend 2016; 159: 142-51.
[3] Mondal AC, Fatima M. Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment. Int J Neurosci 2019; 129: 283-96.
[4] Welch A, Boone R. Sympathetic and parasympathetic responses to specific diversified adjustments to chiropractic vertebral subluxations of the cervical and thoracic spine. J Chiropr Med 2008; 7: 86-93.
[5] Owens A, Low D, Iodice V, Mathias C, Critchley H. Emotion and the autonomic nervous system-a two-way street: insights from affective, autonomic and dissociative disorders. In: Reference Module in Neuroscience and Biobehavioral Psychology, Elsevier, 2017.
[6] Bechara A, Damasio AR. The somatic marker hypothesis: a neural theory of economic decision. Games Econ Behav 2005; 52: 336-72.
[7] Schumann A, Andrack C, Baer K-J. Differences of sympathetic and parasympathetic modulation in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79: 324-331.
[8] Ahern J, Galea S. Collective efficacy and major depression in urban neighborhoods. Am J Epidemiol 2011; 173: 1453-62.
[9] Francis BM, Yang J, Hajderi E, et al. Reduced tissue levels of noradrenaline are associated with behavioral phenotypes of the TgCRND8 mouse model of Alzheimer's disease. Neuropsychopharmacology 2012; 37: 1934-44.
[10] Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C. A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. J Neurosci 2008; 28: 4088-95.
[11] Rottenberg J. Cardiac vagal control in depression: a critical analysis. Biol Psychol 2007; 74: 200-11.
[12] Chang C-C, Tzeng N-S, Yeh C-B, Kuo TB, Huang S-Y, Chang H-A. Effects of depression and melatonergic antidepressant treatment alone and in combination with sedative–hypnotics on heart rate variability: implications for cardiovascular risk. World J Biol Psychiatry 2018; 19: 368-78.
[13] Graur S, Siegle G. Pupillary motility: bringing neuroscience to the psychiatry clinic of the future. Curr Neurol Neurosci Rep 2013; 13: 365.
[14] Latvala A, Kuja-Halkola R, Rück C, et al. Association of resting heart rate and blood pressure in late adolescence with subsequent mental disorders: a longitudinal population study of more than 1 million men in Sweden. JAMA Psychiatry 2016; 73: 1268-75.
[15] Hesse S, Barthel H, Schwarz J, Sabri O, Müller U. Advances in in vivo imaging of serotonergic neurons in neuropsychiatric disorders. Neurosci Biobehav Rev 2004; 28: 547-63.
[16] Chang WH, Lee IH, Chi MH, et al. Prefrontal cortex modulates the correlations between brain-derived neurotrophic factor level, serotonin, and the autonomic nervous system. Sci Rep 2018; 8: 1-9.
[17] Veith RC, Lewis N, Linares OA, et al. Sympathetic nervous system activity in major depression: basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch Gen Psychiatry 1994; 51: 411-22.
[18] Chu ECP, Ng M. Long-term relief from tension-type headache and major depression following chiropractic treatment. J Family Med Prim Care 2018; 7: 629.
[19] Meredith IT, Broughton A, Jennings GL, Esler MD. Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med 1991; 325: 618-24.
[20] Nemeroff CB, Widerlov E, Bissette G, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226: 1342-4.
[21] Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. Int J Neuropsychopharmacol 2003; 6: 225-31.
[22] Vasconcelos AS, Oliveira IC, Vidal LT, et al. Subchronic administration of riparin III induces antidepressive‐like effects and increases BDNF levels in the mouse hippocampus. Fundam Clin Pharmacol 2015; 29: 394-403.
[23] Chen Y-W, Lin P-Y, Tu K-Y, Cheng Y-S, Wu C-K, Tseng P-T. Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review. Neuropsychiatr Dis Treat 2015; 11: 925.
[24] Maltese P, Michelini S, Baronio M, Bertelli M. Molecular foundations of chiropractic therapy. Acta Biomed 2019; 90: 93.
[25] Conway CR, Xiong W. The mechanism of action of vagus nerve stimulation in treatment-resistant depression: current conceptualizations. Psychiatr Clin North Am 2018; 41: 395-407.
[26] Revesz D, Tjernstrom M, Ben-Menachem E, Thorlin T. Effects of vagus nerve stimulation on rat hippocampal progenitor proliferation. Exp Neurol 2008; 214: 259-65.
[27] Carreno FR, Frazer A. Vagal nerve stimulation for treatment-resistant depression. Neurotherapeutics 2017; 14: 716-27.
[28] Gebhardt N, Bär K-J, Boettger MK, et al. Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats. Brain Stimul 2013; 6: 78-83.
[29] Shah A, Carreno FR, Frazer A. Therapeutic modalities for treatment resistant depression: focus on vagal nerve stimulation and ketamine. Clin Psychopharmacol Neurosci 2014; 12: 83-93.
[30] Follesa P, Biggio F, Gorini G, et al. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res 2007; 1179: 28-34.
[31] Budgell BS. Reflex effects of subluxation: the autonomic nervous system. J Manipulative Physiol Ther 2000; 23: 104-6.
[32] Mongini F, Rota E, Deregibus A, et al. Accompanying symptoms and psychiatric comorbidity in migraine and tension-type headache patients. J Psychosom Res 2006; 61: 447-51.
[33] Spain V. Efficacy of manual therapy on frequency and intensity of pain, anxiety and depression in patients with tension-type headache. A randomized controlled clinical trial. Int J Osteopath Med 2016; 22: 11-20.
[34] Bohning DE, Lomarev MP, Denslow S, Nahas Z, Shastri A, George MS. Feasibility of vagus nerve stimulation–synchronized blood oxygenation level–dependent functional MRI. Invest Radiol 2001; 36: 470-9.
[35] Kosel M, Brockmann H, Frick C, Zobel A, Schlaepfer TE. Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex. Psychiatry Res 2011; 191: 153-9.
[36] Mu Q, Bohning DE, Nahas Z, et al. Acute vagus nerve stimulation using different pulse widths produces varying brain effects. Biol Psychiatry 2004; 55: 816-25.
[37] Nahas Z, Marangell LB, Husain MM, et al. Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes. J Clin Psychiatry 2005; 66: 1097-104.
[38] Conway CR, Chibnall JT, Gebara MA, et al. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression. Brain Stimul 2013; 6: 788-97.
[39] Manta S, El Mansari M, Debonnel G, Blier P. Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems. Int J Neuropsychopharmacol 2013; 16: 459-70.
[40] Manta S, Dong J, Debonnel G, Blier P. Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation. J Psychiatry Neurosci 2009; 34: 272.
[41] Sackeim HA, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacol 2001; 25: 713.
[42] Sackeim HA, Brannan SK, Rush AJ, George MS, Marangell LB, Allen J. Durability of antidepressant response to vagus nerve stimulation (VNS). Int J Neuropsychopharmacol 2007; 10: 817-26.
[43] Rong P, Liu J, Wang L, et al. Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. J Affect Disord 2016; 195: 172-9.