Neurobiologische Grundlagen des therapeutischen Einsatzes der repetitiven transkraniellen Magnetstimulation (rTMS) in der Psychiatrie

M. E. Keck

doi:10.1055/s-0038-1624409

Nervenheilkunde, Table of Contents

Nervenheilkunde 2003; 22(05): 253-60
DOI: 10.1055/s-0038-1624409

Original- und Übersichtsarbeiten/Original and Review Articles

Schattauer GmbH

Neurobiologische Grundlagen des therapeutischen Einsatzes der repetitiven transkraniellen Magnetstimulation (rTMS) in der Psychiatrie

The neurobiological basis of therapeutic use of repetitive transcranial magnetic stimulation (rTMS) in psychiatric disorders

M. E. Keck

¹Max-Planck-Institut für Psychiatrie (Direktor: Prof. Dr. Dr. Florian Holsboer)

› Author Affiliations

Abstract

Zusammenfassung

Die therapeutische Anwendung der repetitiven transkraniellen Magnetstimulation (rTMS) wurde in den vergangenen Jahren bei unterschiedlichen psychiatrischen Erkrankungen, wie beispielsweise den unipolaren und bipolaren affektiven Störungen sowie der Schizophrenie, diskutiert. Nach dem Faradayschen Prinzip wird über die Induktion eines Magnetfeldes intrakraniell ein elektrischer Stromfluss erzeugt. Dieser wiederum beeinflusst neuronale Netzwerke in psychopathologisch relevanten Hirnarealen, welche bei psychiatrischen Erkrankungen möglicherweise dysfunktional sind. Conditio sine qua non des gezielten therapeutischen Einsatzes der rTMS sind jedoch Kenntnisse über die zugrunde liegenden, durch rTMS induzierten neurobiologischen Veränderungen. Obgleich der therapeutische Einsatz der rTMS derzeit nur im Rahmen wissenschaftlicher Studien empfohlen werden kann, gibt es ausreichende grundlagenwissenschaftliche Hinweise darauf, dass über rTMS spezifische Veränderungen in neuronalen Schaltkreisen hervorgerufen werden können. Diese zeigen sich tierexperimentell in charakteristischen Verhaltensänderungen sowie in Veränderungen der Aktivität des Stresshormonsystems. Zudem konnten spezifische Änderungen in der Freisetzung von Neuromodulatoren und Neurotransmittern sowie der Genexpression in psychopathologisch relevanten Hirnregionen beschrieben werden. Die bislang untersuchten, durch rTMS induzierten neurobiologischen Mechanismen sind teilweise mit den durch antidepressiv wirksame Substanzen tierexperimentell ausgelösten Effekten

identisch.

Summary

In recent years, the therapeutic properties of repetitive transcranial magnetic stimulation (rTMS) have been investigated for the treatment of various psychiatric disorders such as unipolar and bipolar disorders and schizophrenia. According to Faraday´s law the induction of a magnetic field evokes intracerebral electric currents. This, in turn, influences neuronal networks in psychopathologically relevant brain regions thought to be dysfunctional in psychiatric disorders. In order to optimize rTMS for therapeutic use, however, it is indispensable to understand the neurobiological mechanisms involved. So far, the use of rTMS in the treatment of psychiatric disorders can be recommended only in the context of scientific studies. There is compelling evidence resulting from basic science that rTMS can induce specific alterations in neuronal networks. In animal models, these changes are reflected by characteristic behavioural changes and decreases in the activity of the stress hormone system. In addition, regional changes in neurotransmitter/neuromodulator release and in gene transcription could be demonstrated in relevant brain regions. Together, the mechanisms investigated so far are, in part, reminiscent of those accompanying antidepressant drugs.

Schlüsselwörter

Repetitive transkranielle Magnetstimulation - Depression - Stress - Neurobiologie

Keywords

Repetitive transcranial magnetic stimulation - depression - stress - neurobiology

Full Text

References

Literatur
1 Antoni FA. Vasopressinergic control of pituitary adrenocorticotropin secretion comes of age. Frontiers in Neuroendocrinology 1993; 14: 76-122.
2 Barker AT, Jalinous R, Freeston IL. Non-invasive stimulation of the human motor cortex. Lancet 1985; 01: 1106-7.
3 Belmaker RH, Grisaru N. Magnetic stimulation of the brain in animal depression models responsive to ECS. J ECT 1998; 14: 194-205.
4 Ben-Shachar D. et al. Chronic repetitive transcranial magnetic stimulation alters α-adrenergic and 5-HT2 receptor characteristics in rat brain. Brain Res 1999; 816: 78-83.
5 Benveniste H, Hüttemeier PC. Microdialysis theory and application. Progress in Neurobiology 1990; 35: 195-215.
6 Blier P, de Montigny C. Current advances and trends in the treatment of depression. Trends in Pharmacological Sciences 1994; 15: 220-6.
7 Bohning DE. et al. A combined TMS/fMRI study of intensity-dependent TMS over motor cortex. Biological Psychiatry 1999; 45: 385-94.
8 Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 1999; 89: 999-1002.
9 Cohen E. et al. Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study. J Neurol Neurosurg Psychiatry 1999; 67: 129-30.
10 Crawley JN, Corwin RL. Biological actions of cholecystokinin. Peptides 1994; 05: 731-55.
11 Curt A, Keck ME, Dietz V. Functional outcome following spinal cord injury: Significance of motor-evoked potentials and ASIA scores. Archives of Physical Medicine and Rehabilitation 1998; 79: 81-6.
12 Czéh B. et al. Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biological Psychiatry 2002; 52: 1057-65.
13 Déleuze C, Duvoid A, Hussy N. Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus. J Physiology 1998; 507: 463-71.
14 Diorio D. et al. The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal response to stress. J Neurosci 1993; 13: 3839-47.
15 Fekkes D. et al. Abnormal plasma levels of serine, methionine, and taurine in transient acute polymorphic psychosis. Psychiatry Res 1994; 51: 11-8.
16 Feldman RS. et al. Principles of Neuropsychopharmacology. Mass: Sunderland: Sinauer; 1997
17 Fibiger HC. Neurobiology of depression: focus on dopamine. Depression and Mania 1995; 49: 1-17.
18 File SE. The use of social-interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Meth 1980; 02: 219-38.
19 Fleischmann A. et al. Chronic treatment with repetitive transcranial magnetic stimulation inhibits seizure induction by electroconvulsive shock in rats. Biological Psychiatry 1999; 45: 759-63.
20 Fleischmann A, Prolov K, Abarbanel J, Belmaker RH. The effect of transcranial magnetic stimulation of rat brain on behavior: models of depression. Brain Res 1995; 699: 130-2.
21 Garcia de Yebenes Prous J, Carlsson A, Mena MGomez. The effect of taurine on motor behavior, body temperature, and monoamine metabolism in rat brain. Naunyn Schmiedebergs Arch Pharmacol 1978; 304: 95-9.
22 Groenewegen HJ, Wright CI, Uylings HBM. The anatomical relationship of the prefrontal cortex with limbic structures and the basal ganglia. J Psychopharmacol 1997; 11: 99-106.
23 Grunhaus L. et al. Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Biological Psychiatry 2000; 47: 314-24.
24 Gupta VK. A clinical review of the adaptive role of vasopressin in migraine. Cephalalgia 1997; 17: 561-9.
25 Hausmann A. et al. Chronic repetitive transcranial magnetic stimulation enhances c-fos in the parietal cortex and hippocampus. Mol Brain Res 2000; 76: 355-62.
26 Höflich G, Kasper S, Hufnagel A, Ruhrmann S, Möller HJ. Application of transcranial magnetic stimulation in treatment of drug-resistant major depression a report of two cases. Human Psychopharmacology 1993; 08: 361-5.
27 Holsboer F. Neuroendocrinology of mood disorders. In: Psychopharmacology: The Fourth Generation of Progress. Bloom FE, Kupfer DJ. (eds). New York: Raven Press; 1995: 957-68.
28 Holsboer F. The rationale for corticotropinreleasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatric Res 1999; 33: 181-214.
29 Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477-501.
30 Jacobs BL, Praag H, Gage FH. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 2000; 05: 262-9.
31 Ji RR. et al. Repetitive transcranial magnetic stimulation activates specific regions in rat brain. Proc Natl Acad Sci USA 1998; 95: 15635-40.
32 Keck ME. et al. Repetitive transcranial magnetic stimulation induces active coping strategies and attenuates the neuroendocrine stress response in rats. J Psychiatric Res 2000; 34: 265-76.
33 Keck ME. et al. Ageing alters intrahypothalamic release patterns of vasopressin and oxytocin in rats. Eur J Neurosci 2000; 12: 1487-94.
34 Keck ME, Holsboer F. Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders. Peptides 2001; 22: 835-44.
35 Keck ME. et al. Stumbling reactions in man: influence of corticospinal input. Electroencephal Clin Neurophysiol 1998; 109: 215-23.
36 Keck ME. et al. Acute transcranial magnetic stimulation of frontal brain regions selectively modulates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur J Neurosci 2000; 12: 3713-20.
37 Keck ME. et al. Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Neuropharmacology 2002; 43: 101-9.
38 Keck ME. et al. Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects. Neuropsychopharmacology 2001; 24: 337-49.
39 Keck ME. et al. Vasopressin mediates the response of the combined dexamethasone/ CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders. Neuropsychopharmacology 2002; 26: 94-105.
40 Kole MHP. et al. Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats. Brain Res 1999; 826: 309-12.
41 Landgraf R, Wotjak CT, Neumann ID, Engelmann M. Release of vasopressin within the brain contributes to neuroendocrine and behavioral regulation. In Progress in Brain Research 119. Urban IJA, Burbach JPH, De Wied D. eds. Amsterdam: Elsevier; 1998: 201-20.
42 Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 1997; 08: 523-32.
43 Madsen TM. et al. Increased neurogenesis in a model of electroconvulsive therapy. Biological Psychiatry 2000; 47: 1043-9.
44 Maes M, Verkerk R, Vandoolaeghe E, Lin A, Scharpe S. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiat Scand 1998; 97: 302-8.
45 Malberg JE. et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-10.
46 Mally J, Stone TW. Therapeutic and dose-dependent effect of repetitive microelectroshock induced by transcranial magnetic stimulation in Parkinson´s disease. J Neurosci Res 1999; 57: 935-40.
47 McGarvey KA. et al. ECS-induced dopamine release: effects of electrode placement, anticonvulsant treatment, and stimulus intensity. Biol Psychiatry 1993; 34: 152-7.
48 Mikkelsen JD, Woldbye D, Kragh J, Larsen PJ, Bolwig TG. Electroconvulsive shocks increase the expression of neuropeptide Y (NPY) mRNA in the piriform cortex and dentate gyrus. Mol Brain Res 1994; 23: 317-22.
49 Miyata S, Matsushima O, Hatton GI. Taurine in rat posterior pituitary: localization in astrocytes and selective release by hypoosmotic stimulation. J Comp Neurol 1997; 381: 513-23.
50 Müller MB, Landgraf R, Keck ME. Vasopressin, major depression, and hypothalamic-pituitary-adrenocortical desensitization. Biol Psychiatry 2000; 47: 330-3.
51 Müller MB, Toschi N, Kresse AE, Post A, Keck ME. Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain. Neuropsychopharmacology 2000; 23: 205-15.
52 Nahas Z, Molloy M, Risch SC, George MS. TMS in schizophrenia. In Transcranial magnetic stimulation in neuropsychiatry. George MS, Belmaker RH. eds. Washington DC: American Psychiatric Press Inc; 2000: 237-52.
53 Nibuya M. et al. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995; 15: 7539-47.
54 Padberg F, Möller HJ. Repetitive transcranial magnetic stimulation: Does it have potential in the treatment of depression?. CNS Drugs in press:
55 Pangalos MN. et al. Effect of psychotropic drugs on excitatory amino acids in patients undergoing psychosurgery for depression. Br J Psychiatry 1992; 160: 638-42.
56 Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Meth 1985; 14: 149-67.
57 Post A, Keck ME. Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms?. J Psychiatric Res 2001; 35: 193-215.
58 Post A. et al. Repetitive transcranial magnetic stimulation in rats: evidence for a neuroprotective effect in vitro and in vivo. Eur J Neurosci 1999; 11: 3247-54.
59 Pridmore S. Rapid transcranial magnetic stimulation (rTMS) and normalisation of the dexamethasone suppression test (DST). Psychiatry Clin Neurosci 1999; 53: 33-7.
60 Purba JS, Hoogendijk WJG, Hofman MA, Swaab DF. Increased number of vasopressinand oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 1996; 53: 137-43.
61 Raber J. Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits. Mol Neurobiol 1998; 18: 1-22.
62 Reul JMHM. et al. The brain mineralocorticoid receptor: greedy for ligand, mysterious in function. Eur J Pharmacol 2000; 405: 235-49.
63 Rossini PM. et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots basic principles and procedures for routine clinical application report of an IFCN commitee. Electroencephal Clin Neurophysiol 1994; 91: 79-92.
64 Rossini PM, Rossi S. Clinical applications of motor evoked potentials. Electroencephal Clin Neurophysiol 1998; 106: 180-194.
65 Sackeim HA. et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electro-convulsive therapy. N Engl J Med 1993; 328: 839-46.
66 Scott BW. et al. Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures. Exp Neurol 2000; 165: 231-6.
67 Sesack SR, Pickel VM. Prefrontal cortex efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area. J Comp Neurol 1992; 320: 145-60.
68 Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B. Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson´s disease. J Neurol Sci 2000; 178: 91-4.
69 Strafella AP. et al. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 2001; 21 RC157 1-4.
70 Takayasu M. et al. Triphasic response of rat intracerebral arterioles to increasing concentrations of vasopressin in vitro. J Cereb Blood Flow Metab 1993; 13: 304-9.
71 Thomas DN. et al. Effects of acute and chronic electroconvulsive shock on noradrenaline release in the rat hippocampus and frontal cortex. Br J Pharmacol 1992; 106: 430-4.
72 Van Praag H. et al. Functional neurogenesis in the adult hippocampus. Nature 2002; 415: 1030-4.
73 Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephal Clin Neurophysiol 1998; 108: 1-16.
74 Weissman JD, Epstein CM, Davey KR. Magnetic brain stimulation and brain size relevance to animal studies. Electroencephal Clin Neurophysiol 1992; 85: 215-9.
75 Yoshida K. et al. Dopamine releasing response in rat striatum to single and repeated electroconvulsive shock treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 1997; 21: 707-15.
76 Zis AP, Nomikos GG, Brown EE, Damsma G, Fibiger HC. Neurochemical effects of electrically and chemically induced seizures: an in vivo microdialysis study in the rat hippocampus. Neuropsychopharmacology 1992; 07: 189-95.
77 Zwanzger P. et al. Occurence of Delusions during Repetitive Transcranial Magnetic Stimulation (rTMS) in Major Depression. Biol Psychiatry 2002; 51: 602-3.
78 Zyss T. Deep magnetic brain stimulation – the end of psychiatric electroshock therapy?. Med Hypotheses 1994; 43: 69-74.
79 Zyss T, Gorka Z, Kowalska M, Vetulani J. Preliminary comparison of behavioral and biochemical effects of chronic transcranial magnetic stimulation and electroconvulsive shock in the rat. Biol Psychiatry 1997; 42: 920-4.