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Fortschr Neurol Psychiatr 2001; 69(10): 460-467
DOI: 10.1055/s-2001-17564
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Cholesterin, Omega-3-Fettsäuren und Suizidrisiko

Empirische Evidenz und pathophysiologische HypothesenCholesterol, Omega-3 Fatty Acids, and Suicide Risk: Empirical Evidence and Pathophysiological HypothesesJ.  Brunner1 , K.  G.  Parhofer2 , P.  Schwandt2 , T.  Bronisch1
  • 1 Max-Planck-Institut für Psychiatrie, München (Direktor: Prof. Dr. Dr. F. Holsboer)
  • 2 Medizinische Klinik und Poliklinik II Großhadern, Ludwig-Maximilians-Universität München (Direktor: Prof. Dr. B. Göke)
Diese Arbeit wurde vom Bundesministerium für Bildung und Forschung (BMBF) im Rahmen des Förderschwerpunktes „Kompetenznetze in der Medizin” gefördert.
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Publication Date:
02 October 2001 (online)

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Zusammenfassung

Klinische Studien wiesen bei psychiatrischen Patienten mit verschiedenen Diagnosen auf einen möglichen Zusammenhang zwischen niedrigen Cholesterinkonzentrationen und Suizidalität, Depression, Impulsivität und Aggressivität hin. Diese Assoziation kann nicht allein durch den Gewichtsverlust im Rahmen depressiver Erkrankungen hinreichend erklärt werden. Eine Reihe von Befunden deutet darauf hin, dass ein serotonerges Defizit im präfrontalen Kortex dazu prädisponieren könnte, in psychosozialen Belastungssituationen impulsiv und autoaggressiv zu handeln. Ausgehend von den Befunden zu serotonergen Veränderungen bei suizidalen Patienten wurde eine neurobiologisch determinierte Vulnerabilität für suizidales Verhalten postuliert. In-vitro-Untersuchungen und Tierexperimente sowie humane In-vivo-Studien unterstützen die Annahme, dass eine Cholesterinreduktion in neuronalen Membranen die serotonerge Neurotransmission hemmen könnte. Aufgrund neuester Befunde wurde die Hypothese formuliert, dass ein Mangel an mehrfach ungesättigten Fettsäuren, insbesondere Omega-3-Fettsäuren, das Risiko für Depressionen und Suizidhandlungen erhöhen könnte. Untersuchungen an gesunden Probanden deuten darauf hin, dass eine erhöhte Zufuhr von Omega-3-Fettsäuren mit der Nahrung die serotonerge Aktivität erhöhen und dadurch impulsive und aggressive Verhaltensweisen hemmen könnte. Frühere epidemiologische Studien zeigten eine statistische Assoziation zwischen niedrigen Cholesterinspiegeln und einem erhöhten Suizidrisiko. Dies konnte jedoch in neueren epidemiologischen Untersuchungen mit größeren Fallzahlen und längeren Beobachtungszeiträumen nicht repliziert werden; vielmehr zeigte sich sogar eine positive Korrelation zwischen Cholesterinkonzentrationen und Suizidrisiko. Die kürzlich publizierten Interventionsstudien zeigten, dass Statine (Simvastatin, Lovastatin, Pravastatin) nicht zu einer Erhöhung der Suizidmortalität führen.

Abstract

Studies in psychiatric patients described an association between lower serum cholesterol concentrations, suicidality, depression, impulsivity, and aggression which is not entirely attributable to depression-related malnutrition and weight-loss. Several lines of evidence suggest that a serotonergic deficit in the prefrontal cortex may predispose vulnerable subjects to impulsive, autoaggressive, and suicidal behaviour in stressful life-events. In-vitro studies, animal experiments, and human in-vivo studies support the hypothesis that cholesterol reduction may contribute to the serotonergic abnormalities which have been postulated in suicidal subjects. Recently it was hypothesized that decreased consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, may be a risk factor for depression and suicide. Data from human studies in healthy volunteers suggest that increasing the dietary intake of omega-3 fatty acids may increase central serotonergic activity and reduce impulsive and aggressive behaviours. Earlier epidemiological studies showed an association between low cholesterol concentrations and increased suicide risk. Recent epidemiological studies with greater samples and longer follow-up periods, however, even showed a positive correlation between cholesterol concentrations and suicide risk after controlling for potential confounding variables. Large trials of statins (simvastatin, lovastatin, pravastatin) did not show an increase of suicide mortality.

Literatur

  • 1 Papassotiropoulos A, Hawellek B, Frahnert C, Rao G S, Rao M L. The risk of acute suicidality in psychiatric inpatients increases with low plasma cholesterol.  Pharmacopsychiat. 1999;  32 1 - 4
    PubMedGoogle Scholar
  • 2 Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel V, Neels H, Demedts P, Wauters A, Meltzer H Y. Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers.  Acta Psychiatr Scand. 1997;  95 212 - 221
    PubMedGoogle Scholar
  • 3 Kunugi H, Takei N, Aoki H, Nanko S. Low serum cholesterol in suicide attempters.  Biol Psychiatry. 1997;  41 196 - 200
    CrossrefPubMedGoogle Scholar
  • 4 Yeragani V K, Balon R, Pohl R, Ramesh C. Imipramine treatment and increased serum cholesterol levels.  Canadian Journal of Psychiatry. 1989;  34 (8) 845
    PubMedGoogle Scholar
  • 5 Brown D W, Ketter T A, Crumlish J, Post R M. Carbamazepine-induced increases in total serum cholesterol: clinical and theoretical implications.  J Clin Psychopharmacol. 1992;  12 431- 437
    PubMedGoogle Scholar
  • 6 Spivak B, Lamschtein C, Talmon Y, Guy N, Mester R, Feinberg I, Kotler M, Weizman A. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients.  Clinical Neuropharmacology. 1999;  22 (2) 98 - 101
    PubMedGoogle Scholar
  • 7 Morgan R E, Palinkas L A, Barrett-Connor E L, Wingard D L. Plasma cholesterol and depressive symptoms in older men.  Lancet. 1993;  341 75 -79
    CrossrefPubMedGoogle Scholar
  • 8 Horsten M, Wamala S P, Vingerhoets A, Orth-Gomer K. Depressive symptoms, social support, and lipid profile in healthy middle-aged women.  Psychosomatic Medicine. 1997;  59 521 - 528
    PubMedGoogle Scholar
  • 9 Bronisch T. The relationship between suicidality and depression.  Archives of Suicide Research. 1996;  2 235 - 254
    PubMedGoogle Scholar
  • 10 Brunner J, Bronisch T. Neurobiologische Korrelate suizidalen Verhaltens.  Fortschr Neurol Psychiat. 1999;  67 391 - 412
    PubMedGoogle Scholar
  • 11 Virkkunen M. Serum cholesterol levels in homicidal offenders.  Neuropsychobiology. 1983;  10 65 - 69
    PubMedGoogle Scholar
  • 12 Golomb B A, Stattin H, Mednick S. Low cholesterol and violent crime.  Journal of Psychiatric Research. 2000;  34 301 - 309
    CrossrefPubMedGoogle Scholar
  • 13 Freedman D S, Byers T, Barrett D H, Stroup N E, Eaker E, Monroe-Blum H. Plasma lipid levels and psychologic characteristics in men.  Am J Epidemiol. 1995;  141 507 - 517
    PubMedGoogle Scholar
  • 14 New A S, Sevin E M, Mitropoulou V, Reynolds D, Novotny S L, Callahan A, Trestman R L, Siever L J. Serum cholesterol and impulsivity in personality disorders.  Psychiatry Res. 1999;  85 145 - 150
    CrossrefPubMedGoogle Scholar
  • 15 Steinert T, Woelfle M, Gebhardt R P. No correlation of serum cholesterol levels with measures of violence in patients with schizophrenia and non-psychotic disorders.  Eur Psychiatry. 1999;  14 346 - 348
    CrossrefPubMedGoogle Scholar
  • 16 Lester D. The concentration of neurotransmitter matabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis.  Pharmacopsychiat. 1995;  28 45 - 50
    PubMedGoogle Scholar
  • 17 Mann J J. The neurobiology of suicide.  Nature Medicine. 1998;  4 25 - 30
    CrossrefPubMedGoogle Scholar
  • 18 Engelberg H. Low serum cholesterol and suicide.  Lancet. 1992;  339 727 - 729
    CrossrefPubMedGoogle Scholar
  • 19 Hawton K, Cowen P, Owens D, Bond A, Elliott M. Low serum cholesterol and suicide.  Br J Psychiatry. 1993;  162 818 - 825
    PubMedGoogle Scholar
  • 20 Fawcett J, Busch K A, Jacobs D, Kravitz H M, Fogg L. Suicide: a four-pathway clinical-biochemical model.  Ann NY Acad Sci. 1997;  836 288 - 301
    PubMedGoogle Scholar
  • 21 Block E R, Edwards D. Effect of plasma membrane fluidity on serotonin transport by endothelial cells.  Am J Physiology. 1987;  253 C672 - C678
    PubMedGoogle Scholar
  • 22 Heron D S, Shinitzky M, Hershkowitz M, Samuel D. Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes.  Proc Natl Acad Sci USA. 1980;  77 (12) 7463 - 7467
    PubMedGoogle Scholar
  • 23 Shih J C, Ohsawa R. Differential effect of cholesterol on two types of 5-hydroxytryptamine binding sites.  Neurochemical Research. 1983;  8 (6) 701 - 710
    CrossrefPubMedGoogle Scholar
  • 24 Papaphilis A, Deliconstantinos G. Modulation of serotonergic receptors by exogenous cholesterol in the dog synaptosomal plasma membrane.  Biochemical Pharmacology. 1980;  29 3325 - 3327
    CrossrefPubMedGoogle Scholar
  • 25 Maguire P A, Druse M J. The influence of cholesterol on synaptic fluidity, dopamine D1 binding and dopamine-stimulated adenylate cyclase.  Brain Res Bull. 1989;  23 69 - 74
    CrossrefPubMedGoogle Scholar
  • 26 Salter M. Low serum cholesterol and suicide.  Lancet. 1992;  339 1169
    CrossrefPubMedGoogle Scholar
  • 27 Kaplan J R, Shively C A, Fontenot M B, Morgan T M, Howell S M, Manuck S B, Muldoon M F, Mann J J. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys.  Psychosomatic Medicine. 1994;  56 479 - 484
    PubMedGoogle Scholar
  • 28 Muldoon M F, Kaplan J R, Manuck S B, Mann J J. Effects of a low-fat diet on brain serotonergic responsivity in cynomolgus monkeys.  Biol Psychiatry. 1992;  31 739 - 742
    CrossrefPubMedGoogle Scholar
  • 29 Kaplan J R, Muldoon M F, Manuck S B, Mann J J. Assessing the observed relationship between low cholesterol and violence-related mortality. Implications for suicide risk.  Ann NY Acad Sci. 1997;  836 57 - 80
    PubMedGoogle Scholar
  • 30 Steegmans P HA, Fekkes D, Hoes A W, Bak A AA, van der Does E, Grobbee D E. Low serum cholesterol concentrations and serotonin metabolism in men.  Br Med J. 1996;  312 221
    PubMedGoogle Scholar
  • 31 Ringo D L, Lindley S E, Faull K F, Faustman W O. Cholesterol and serotonin: seeking a possible link between blood cholesterol and CSF 5-HIAA.  Biol Psychiatry. 1994;  35 957 - 959
    CrossrefPubMedGoogle Scholar
  • 32 Alvarez J C, Cremniter D, Lesieur P, Gregoire A, Gilton A, Macquin-Mavier I, Jarreau C, Spreux-Varoquaux O. Low blood cholesterol and low platelet serotonin levels in violent suicide attempters.  Biol Psychiatry. 1999;  45 1066 - 1069
    CrossrefPubMedGoogle Scholar
  • 33 Severus W E, Ahrens B. Omega-3 fatty acids in psychiatry.  Nervenarzt. 2000;  71 58 - 62
    CrossrefPubMedGoogle Scholar
  • 34 Hibbeln J R, Umhau J C, George D T, Salem N. Do plasma polyunsaturates predict hostility and depression?. In: Simopoulos, AP, Pavlou, KN (Hrsg.). Nutrition and Fitness: Metabolic and Behavioral Aspects in Health and Disease. World Rev Nutr Diet Basel: Karger 1997: 175-186
    Google Scholar
  • 35 Hibbeln J R, Salem N. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy.  Am J Clin Nutr. 1995;  62 1 - 9
    PubMedGoogle Scholar
  • 36 Adams P B, Lawson S, Sanigorski A, Sinclair A J. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.  Lipids. 1996;  31 (suppl) 157 - 161
    PubMedGoogle Scholar
  • 37 Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H. Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased C20 : 4ω3/C20 : 5ω3 ratio in cholesteryl esters and phospholipids.  Journal of Affective Disorders. 1996;  38 35 - 46
    CrossrefPubMedGoogle Scholar
  • 38 Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer H Y. Lowered ω3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients.  Psychiatry Res. 1999;  85 275 - 291
    CrossrefPubMedGoogle Scholar
  • 39 Holsboer F. The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety.  Journal of Psychiatric Research. 1999;  33 181- 214
    CrossrefPubMedGoogle Scholar
  • 40 Stoll A L, Severus E, Freeman M P, Rueter S, Zboyan H A, Diamond E, Cress K K, Marangell L B. Omega 3 fatty acids in bipolar disorder. A preliminary double-blind, placebo-controlled trial.  Arch Gen Psychiatry. 1999;  56 407- 412
    PubMedGoogle Scholar
  • 41 Delion S, Chalon S, Hérault J, Guilloteau D, Besnard J C, Durand G. Chronic dietary α-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats.  J Nutr. 1994;  124 2466 - 2476
    PubMedGoogle Scholar
  • 42 Hibbeln J R, Linnoila M, Umhau J C, Rawlings R, George D T, Salem N. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics.  Biol Psychiatry. 1998;  44 235 - 242
    CrossrefPubMedGoogle Scholar
  • 43 Virkkunen M E, Horrobin D F, Jenkins D K, Manku M S. Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent, and impulsive offenders.  Biol Psychiatry. 1987;  22 1087 - 1096
    CrossrefPubMedGoogle Scholar
  • 44 Hamazaki T, Sawazaki M, Asaoka E, Nagao Y, Nishimura N, Yazawa K, Kuwamori T, Kobayashi M. The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study.  J Clin Invest. 1996;  97 1129 - 1133
    PubMedGoogle Scholar
  • 45 Hibbeln J R, Umhau J C, Linnoila M, George D T, Ragan P W, Shoaf S E, Vaughan M R, Rawlings R, Salem N. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids.  Biol Psychiatry. 1998;  44 243 - 249
    CrossrefPubMedGoogle Scholar
  • 46 Vartiainen E, Puska P, Pekkanen J, Tuomilehto J, Lönnqvist J, Ehnholm C. Serum cholesterol concentrations and mortality from accidents, suicide, and other violent causes.  Br Med J. 1994;  13 445 - 447
    PubMedGoogle Scholar
  • 47 Zureik M, Courbon D, Ducimetière P. Serum cholesterol concentration and death from suicide in men: Paris prospective study I.  Br Med J. 1996;  313 649 - 651
    PubMedGoogle Scholar
  • 48 Partonen T, Haukka J, Virtamo J, Taylor P R, Lönnqvist J. Association of low serum total cholesterol with major depression and suicide.  British Journal of Psychiatry. 1999;  175 259 - 262
    PubMedGoogle Scholar
  • 49 Iribarren C, Reed D M, Wergowske G, Burchfiel C M, Dwyer J H. Serum cholesterol level and mortality due to suicide and trauma in the Honolulu heart program.  Arch Int Med. 1995;  155 695 - 700
    PubMedGoogle Scholar
  • 50 Tanskanen A, Vartiainen E, Tuomilehto J, Viinamäki H, Lehtonen J, Puska P. High serum cholesterol and risk of suicide.  Am J Psychiatry. 2000;  157 648 - 650
    CrossrefPubMedGoogle Scholar
  • 51 Muldoon M, Manuck S B, Matthews K A. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.  Br Med J. 1990;  301 309-314
    PubMedGoogle Scholar
  • 52 LaRosa J C. Cholesterol lowering and morbidity and mortality.  Current Opinion in Lipidology. 1995;  6 62 - 65
    PubMedGoogle Scholar
  • 53 Richter W O. Vermehrte Autoaggressivität durch cholesterinsenkende Medikamente?.  Fortschr Med. 1994;  112 507 - 508
    PubMedGoogle Scholar
  • 54 Muldoon M, Rossouw J E, Manuck S E, Glueck C J, Kaplan J R, Kaufmann P G. Low or lowered cholesterol and risk of death from suicide and trauma.  Metabolism. 1993;  42 (9 Suppl 1) 45 - 56
    CrossrefPubMedGoogle Scholar
  • 55 Rubins B H, Robins S J, Collins D, Fye C L, Anderson J W, Elam M B, Faas F H, Linares E, Schaefer E J, Schectman G, Wilt T J, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol.  N Engl J Med. 1999;  341 410 - 418
    CrossrefPubMedGoogle Scholar
  • 56 Duits N, Bos F M. Depressive symptoms and cholesterol-lowering drugs.  Lancet. 1993;  341 114
    PubMedGoogle Scholar
  • 57 Lechleitner M, Hoopichler F, Konwalinka G, Patsch J R, Braunsteiner H. Depressive symptoms in hypercholesterolaemic patients treated with pravastatin.  Lancet. 1992;  340 910
    PubMedGoogle Scholar
  • 58 Delva N J. Matthews DR. Cowen PJ. Brain serotonin (5-HT) neuroendocrine function in patients taking cholesterol-lowering drugs.  Biol Psychiatry. 1996;  39 100 - 106
    CrossrefPubMedGoogle Scholar
  • 59 Scandinavian Simvastatin Survival Study G roup. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S).  Lancet. 1994;  344 1383 - 1389
    PubMedGoogle Scholar
  • 60 Shepherd J, Cobbe S M, Ford I, Isles C G, Lorimer A R, MacFarlane P W, McKillop J H, Packard C J. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.  N Engl J Med. 1995;  333 (20) 1301 - 1307
    CrossrefPubMedGoogle Scholar
  • 61 Downs J R, Clearfield M, Weis S, Whitney E, Shapiro D R, Beere P A, Langendorfer A, Stein E A, Kruyer W, Gotto A M. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels.  JAMA. 1998;  279 1615 -1622
    CrossrefPubMedGoogle Scholar
  • 62 Sacks F M, Pfeffer M A, Moye L A, Rouleau J L, Rutherford J D, Cole T G, Brown L, Warnica J W, Arnold J MO, Wun C C, Davis B R, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.  N Engl J Med. 1996;  335 101 - 109
    PubMedGoogle Scholar
  • 63 The long-term intervention with pravastatin in ischaemic disease (LIPID) study g roup. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.  N Engl J Med. 1998;  339 1349 - 1357
    CrossrefPubMedGoogle Scholar
  • 64 LaRosa J C, He J, Vupputuri S. Effects of statins on risk of coronary heart disease. A meta-analysis of randomized controlled trials.  JAMA. 1999;  282 2340 - 2346
    CrossrefPubMedGoogle Scholar
  • 65 Strandberg T E, Räikkönen K, Partinen M, Pihl S, Vanhanen H, Miettinen T A. Associations of cholesterol lowering by statins with anger and hostility in hypercholesterolemic men.  Biol Psychiatry. 1994;  35 575 - 577
    CrossrefPubMedGoogle Scholar
  • 66 Fritze J, Schneider B, Lanczik M. Autoaggressive behaviour and cholesterol.  Neuropsychobiology. 1992;  26 180 - 181
    PubMedGoogle Scholar
  • 67 Modai I, Valevski A, Dror S, Weizman A. Serum cholesterol levels and suicidal tendencies in psychiatric inpatients.  J Clin Psychiatry. 1994;  55 252 - 254
    PubMedGoogle Scholar
  • 68 Sullivan P F, Joyce P R, Bulik C M, Mulder R T, Oakley-Browne M. Total cholesterol and suicidality in depression.  Biol Psychiatry. 1994;  36 472 - 477
    CrossrefPubMedGoogle Scholar
  • 69 Gallerani M, Manfredini R, Caracciolo S, Scapoli C, Molinari S, Fersini C. Serum cholesterol concentrations in parasuicide.  Br Med J. 1995;  310 1632 - 1636
    PubMedGoogle Scholar
  • 70 Golier J A, Marzuk P M, Leon A C, Weiner C, Tardiff K. Low serum cholesterol level and attempted suicide.  Am J Psychiatry. 1995;  152 419 - 423
    PubMedGoogle Scholar
  • 71 Wolfersdorf M, Michelsen A, Keller F, Maier V, Fröscher W, Kaschka W P. Serum cholesterol, triglyceride and suicide in depressed patients.  Archives of Suicide Research. 1996;  2 161 - 170
    PubMedGoogle Scholar
  • 72 Apter A, Laufer N, Bar-Sever M, Har-Even D, Ofek H, Weizman A. Serum cholesterol, suicidal tendencies, impulsivity, aggression, and depression in adolescent psychiatric inpatients.  Biol Psychiatry. 1999;  46 532 - 541
    CrossrefPubMedGoogle Scholar
  • 73 Glueck C J, Tieger M, Kunkel R, Hamer T, Tracy T, Speirs J. Hypocholesterolemia and affective disorders.  Am J Med Sci. 1994;  308 (4) 218 - 225
    PubMedGoogle Scholar
  • 74 Maes M, Delanghe J, Meltzer H Y, Scharpé S, D’Hondt P, Cosyns P. Lower degree of esterification of serum cholesterol in depression: relevance for depression and suicide research.  Acta Psychiatr Scand. 1994;  90 252 - 258
    PubMedGoogle Scholar
  • 75 Lindberg G, Larsson G, Setterlind S, Råstam L. Serum lipids and mood in working men and women in Sweden.  J Epidemiol Community Health. 1994;  48 360 - 363
    PubMedGoogle Scholar

Dr. med. Jürgen Brunner

Max-Planck-Institut für Psychiatrie

Kraepelinstraße 10

80804 München

Email: E-mail: jbrunner@mpipsykl.mpg.de

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