Elektrokonvulsive Therapie bei Depression: Welche Erkenntnisse erbringen fMRT-, PET- und SPECT-Untersuchungen?

Zusammenfassung

Die elektrokonvulsive Therapie (EKT) zeigt überlegene klinische Wirksamkeit bei therapieresistenter Depression. Befunde aus nuklearmedizinischen und funktionellen magnetresonanztomografischen (fMRT) Untersuchungen zur EKT können zunehmend im Kontext pathophysiologischer Modelle von Depression interpretiert werden und leisten einen Beitrag zur Validierung von Theorien zum Wirkmechanismus von EKT. Modellvorstellungen depressiver Störungen postulieren eine dysfunktionale Modulation von Gehirnaktivität innerhalb kortiko-limbischer Regelkreise sowie eine aberrante Interaktion von funktionellen zerebralen Netzwerken, die an emotionalen Prozessen beteiligt sind. Nuklearmedizinische Methoden haben konvergierende Belege für iktale Gehirnfunktionsänderungen im Rahmen von EKT erbracht, die spezifisch mit klinischer Wirkung und Nebenwirkungen assoziiert zu sein scheinen; bezüglich länger anhaltender zerebraler Effekte nach EKT bestehen Hinweise für z. T. weitreichende Gehirnfunktionsänderungen, die sich allerdings sowohl in vergleichender Wertung untereinander als auch im Kontext von Annahmen zur funktionellen Neuroanatomie von Depression nicht übereinstimmend interpretieren lassen. Mittels fMRT wurden erste überzeugende Belege für EKT-induzierte, interiktal überdauernde Veränderungen der Interaktion von zerebralen Strukturen vorgelegt, deren Relevanz in der Pathophysiologie von Depression als gesichert angenommen werden kann. Ein konsistentes Modell über den Wirkmechanismus von EKT kann ausgehend von diesen Befunden gleichwohl gegenwärtig nicht formuliert werden. Ein weiterreichendes Verständnis des Einflusses von EKT auf die Pathophysiologie depressiver Störungen könnte in der Etablierung von Biomarkern zur Prädiktion von Behandlungsresponse und/oder unerwünschten Nebenwirkungen eine klinisch hilfreiche Anwendung finden.

Abstract

Electroconvulsive therapy (ECT) is the most potent and rapidly acting of all antidepressant treatments in major depressive disorder (MDD). Nuclear and functional magnetic (fMRI) brain imaging studies of ECT have substantially contributed to the neurobiological understanding of this treatment modality. Neuroimaging methods may also validate potential mechanisms of antidepressant action. Models of neural dysfunction in MDD suggest impaired modulation of activity within a cortico-limbic circuitry, along with alterations in the functional organisation of multiple brain networks implicated in emotional processes. Nuclear imaging techniques have demonstrated consistent patterns of ECT-induced ictal changes in brain activity that appear to be linked to efficacy and side effects of ECT. Interictally, widespread alterations of brain function have been reported, however, results remain inconclusive. FMRI studies of ECT have demonstrated longer-lasting, interictal changes of neural activity in multiple cerebral regions that are in accordance with functional neuroanatomical models of mood disorders. Future research detailing ECT interactions with brain pathophysiology in MDD could potentially provide a clinically useful framework to better predict ECT treatment response and/or side effects, and may also facilitate the development of more focused brain stimulation techniques.

Schlüsselwörter

Elektrokonvulsive Therapie - EKT - Depression - fMRT - PET - SPECT

Key words

electroconvulsive therapy - ECT - depression - fMRI - PET - SPECT

• Literatur

• 1 Fink M. ECT has proved effective in treating depression. Nature 2000; 403: 826
• 2 Husain MM, Rush AJ, Fink M et al. Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a Consortium for Research in ECT (CORE) report. J Clin Psychiatry 2004; 65: 485-491
• 3 Ottosson JO. Experimental studies of the mode of action of electroconvulsive therapy: Introduction. Acta Psychiatr Scand Suppl 1960; 35: 5-6
• 4 Folkerts HW. Electroconvulsive therapy. Indications, procedure and treatment results. Nervenarzt 2011; 82: 93-102 , quiz 103
• 5 Swartz CM. Electroconvulsive and Neuromodulation Therapies. 1. Aufl. New York: Cambridge University Press; 2009
• 6 Devanand DP, Dwork AJ, Hutchinson ER et al. Does ECT alter brain structure?. Am J Psychiatry 1994; 151: 957-970
• 7 Ackermann RF, Engel J, Baxter Jr L. Positron emission tomography and autoradiographic studies of glucose utilization following electroconvulsive seizures in humans and rats. Ann N Y Acad Sci 1986; 462: 263-269
• 8 Lajoie C, Levasseur MA, Paquet N. Complete normalization of severe brain 18F-FDG hypometabolism following electroconvulsive therapy in a major depressive episode. Clin Nucl Med 2013; 38: 735-736
• 9 Anghelescu I, Klawe CJ, Bartenstein P et al. Normal PET after long-term ECT. Am J Psychiatry 2001; 158: 1527
• 10 Conca A, Fritzsche H, Peschina W et al. Preliminary findings of simultaneous 18F-FDG and 99mTc-HMPAO SPECT in patients with depressive disorders at rest: differential correlates with ratings of anxiety. Psychiatry Res 2000; 98: 43-54
• 11 Sermet E, Gregoire MC, Galy G et al. Paradoxical metabolic response of the human brain to a single electroconvulsive shock. Neurosci Lett 1998; 254: 41-44
• 12 Yuuki N, Ida I, Oshima A et al. HPA axis normalization, estimated by DEX/CRH test, but less alteration on cerebral glucose metabolism in depressed patients receiving ECT after medication treatment failures. Acta Psychiatr Scand 2005; 112: 257-265
• 13 Bajc MB M, Topuzovic N, Babic D et al. Acute effect of electroconvulsive therapy on brain perfusion assessed by Tc99m-hexamethylpropyleneamineoxim and single photon emission computed tomography. Acta Psychiatr Scand 1989; 80: 421-426
• 14 Rosenberg RV S, Andersen A, Blowig TG. Effect of ECT on Cerebral Blood Flow in Melancholia Assessed with SPECT. Convuls Ther 1988; 4: 62-73
• 15 Silfverskiold P, Rosen I, Risberg J. Effects of electroconvulsive therapy on EEG and cerebral blood flow in depression. Eur Arch Psychiatry Neurol Sci 1987; 236: 202-208
• 16 Elizagarate E, Cortes J, Gonzalez Pinto A et al. Study of the influence of electroconvulsive therapy on the regional cerebral blood flow by HMPAO-SPECT. J Affect Disord 2001; 65: 55-59
• 17 Escobar R, Rios A, Montoya ID et al. Clinical and cerebral blood flow changes in catatonic patients treated with ECT. J Psychosom Res 2000; 49: 423-429
• 18 Breker D, Bohnen NI. Single case study of brain FDG PET imaging in a patient with catatonia. Clin Nucl Med 2013; 38: 297-298
• 19 Moretti A, Gorini A, Villa RF. Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry 2003; 8: 773-785
• 20 Neirinckx RD, Canning LR, Piper IM et al. Technetium-99m d, l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion. J Nucl Med 1987; 28: 191-202
• 21 Blumenfeld H, Westerveld M, Ostroff RB et al. Selective frontal, parietal, and temporal networks in generalized seizures. NeuroImage 2003; 19: 1556-1566
• 22 Blumenfeld H, McNally KA, Ostroff RB et al. Targeted prefrontal cortical activation with bifrontal ECT. Psychiatry Research: Neuroimaging 2003; 123: 165-170
• 23 Enev M, McNally KA, Varghese G et al. Imaging onset and propagation of ECT-induced seizures. Epilepsia 2007; 48: 238-244
• 24 Takano H, Motohashi N, Uema T et al. Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression: Positron emission tomographic study. The British Journal of Psychiatry 2007; 190: 63-68
• 25 Takano H, Motohashi N, Uema T et al. Differences in cerebral blood flow between missed and generalized seizures with electroconvulsive therapy: a positron emission tomographic study. Epilepsy Res 2011; 97: 225-228
• 26 Bonne O, Krausz Y, Shapira B et al. Increased cerebral blood flow in depressed patients responding to electroconvulsive therapy. J Nucl Med 1996; 37: 1075-1080
• 27 Mervaala E, Könönen M, Föhr J et al. SPECT and neuropsychological performance in severe depression treated with ECT. J Affect Disord 2001; 66: 47-58
• 28 Scott AIF, Dougall N, Ross M et al. Short-term effects of electroconvulsive treatment on the uptake of99mTc-Exametazime into brain in major depression shown with single photon emission tomography. J Affect Disord 1994; 30: 27-34
• 29 Vangu MDT, Esser JD, Boyd IH et al. Effects of electroconvulsive therapy on regional cerebral blood flow measured by 99mtechnetium HMPAO SPECT. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2003; 27: 15-19
• 30 Awata S, Konno M, Kawashima R et al. Changes in regional cerebral blood flow abnormalities in late-life depression following response to electroconvulsive therapy. Psychiatry Clin Neurosci 2002; 56: 31-40
• 31 Kohn Y, Freedman N, Lester H et al. 99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression. J Nucl Med 2007; 48: 1273-1278
• 32 Milo TJ, Kaufman GE, Barnes WE et al. Changes in regional cerebral blood flow after electroconvulsive therapy for depression. J ECT 2001; 17: 15-21
• 33 Bonne O, Louzoun Y, Aharon I et al. Cerebral blood flow in depressed patients: a methodological comparison of statistical parametric mapping and region of interest analyses. Psychiatry Research: Neuroimaging 2003; 122: 49-57
• 34 Schmidt EZ, Reininghaus B, Enzinger C et al. Changes in brain metabolism after ECT-positron emission tomography in the assessment of changes in glucose metabolism subsequent to electroconvulsive therapy – lessons, limitations and future applications. J Affect Disord 2008; 106: 203-208
• 35 Henry ME, Schmidt ME, Matochik JA et al. The effects of ECT on brain glucose: a pilot FDG PET study. J ECT 2001; 17: 33-40
• 36 Nobler MS, Oquendo MA, Kegeles LS et al. Decreased regional brain metabolism after ect. Am J Psychiatry 2001; 158: 305-308
• 37 Guze BH, Baxter Jr LR, Schwartz JM et al. Electroconvulsive Therapy and Brain Glucose Metabolism. Convuls Ther 1991; 7: 15-19
• 38 Volkow ND, Bellar S, Mullani N et al. Effects of Electroconvulsive Therapy on Brain Glucose Metabolism: A Preliminary Study. Convuls Ther 1988; 4: 199-205
• 39 Yatham LN, Clark CC, Zis AP. A preliminary study of the effects of electroconvulsive therapy on regional brain glucose metabolism in patients with major depression. J ECT 2000; 16: 171-176
• 40 Reininghaus EZ, Reininghaus B, Ille R et al. Clinical effects of electroconvulsive therapy in severe depression and concomitant changes in cerebral glucose metabolism ­– An exploratory study. J Affect Disord 2013; 146: 290-294
• 41 Suwa T, Namiki C, Takaya S et al. Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT. J Affect Disord 2012; 136: 1039-1046
• 42 McCormick LM, Boles Ponto LL, Pierson RK et al. Metabolic correlates of antidepressant and antipsychotic response in patients with psychotic depression undergoing electroconvulsive therapy. J ECT 2007; 23: 265-273
• 43 Abbott CC, Lemke NT, Gopal S et al. Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation. Front Psychiatry 2013; 4: 10
• 44 Beall EB, Malone DA, Dale RM et al. Effects of electroconvulsive therapy on brain functional activation and connectivity in depression. J ECT 2012; 28: 234-241
• 45 Perrin JS, Merz S, Bennett DM et al. Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proc Natl Acad Sci U S A 2012; 109: 5464-5468
• 46 Sheline YI, Price JL, Yan Z et al. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A 2010; 107: 11020-11025
• 47 Vasic N, Walter H, Sambataro F et al. Aberrant functional connectivity of dorsolateral prefrontal and cingulate networks in patients with major depression during working memory processing. Psychol Med 2009; 39: 977-987
• 48 Xie C, Goveas J, Wu Z et al. Neural basis of the association between depressive symptoms and memory deficits in nondemented subjects: resting-state fMRI study. Hum Brain Mapp 2012; 33: 1352-1363
• 49 Raichle ME, MacLeod AM, Snyder AZ et al. A default mode of brain function. Proc Natl Acad Sci U S A 2001; 98: 676-682
• 50 Andrews-Hanna JR, Reidler JS, Sepulcre J et al. Functional-anatomic fractionation of the brain's default network. Neuron 2010; 65: 550-562
• 51 Wang L, Hermens DF, Hickie IB et al. A systematic review of resting-state functional-MRI studies in major depression. J Affect Disord 2012; 142: 6-12
• 52 Sambataro FW, Wolf ND, Giusti P et al. Default mode network in depression: a pathway to impaired affective cognition?. Clinical Neuropsychiatry 2013; 10: 212-216
• 53 Beckmann CF. Modelling with independent components. NeuroImage 2012; 62: 891-901
• 54 Fitzgerald PB, Laird AR, Maller J et al. A meta-analytic study of changes in brain activation in depression. Hum Brain Mapp 2008; 29: 683-695
• 55 Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull 2003; 65: 193-207
• 56 Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology 2010; 35: 192-216
• 57 Diener C, Kuehner C, Brusniak W et al. A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression. NeuroImage 2012; 61: 677-685
• 58 Friston KJ. Functional and effective connectivity in neuroimaging: A synthesis. Hum Brain Mapp 1994; 2: 56-78
• 59 Sambataro F, Wolf ND, Pennuto M et al. Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity. Psychol Med 2013; DOI: 10.1017/s0033291713002596.
• 60 Zhou Y, Yu C, Zheng H et al. Increased neural resources recruitment in the intrinsic organization in major depression. J Affect Disord 2010; 121: 220-230
• 61 Fox MD, Snyder AZ, Vincent JL et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 2005; 102: 9673-9678
• 62 Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 2011; 36: 183-206
• 63 Delaveau P, Jabourian M, Lemogne C et al. Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies. J Affect Disord 2011; 130: 66-74
• 64 Anand A, Li Y, Wang Y et al. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. J Neuropsychiatry Clin Neurosci 2007; 19: 274-282
• 65 Kuhn J, Gaebel W. Therapeutische Stimulationsverfahren für psychiatrische Erkrankungen. 1. Aufl. Stuttgart: W. Kohlhammer;
• 66 Sacher J, Neumann J, Funfstuck T et al. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J Affect Disord 2012; 140: 142-148
• 67 Sheline YI, Barch DM, Price JL et al. The default mode network and self-referential processes in depression. Proc Natl Acad Sci U S A 2009; 106: 1942-1947