Zur Beziehung von psychologischem Stress und klinischem Verlauf der multiplen Sklerose

Zusammenfassung

Der Zusammenhang zwischen psychologischem Stress und Verlauf der MS ist in zahlreichen Studien mit unterschiedlicher methodischer Qualität untersucht worden. Die Mehrheit der Befunde deutet darauf hin, dass ein akuter, kurzfristiger Stressor keine negativen Auswirkungen hat. Dagegen sind chronische psychosoziale Stressoren wie interpersonale Konflikte, unverarbeitete Verlusterlebnisse, subjektiv empfundener Mangel an sozialer Unterstützung, Ängste und depressive Episoden als mögliche schubfördernde Risikofaktoren anzusehen. Die neuroimmunologischen Befunde bei der MS und verschiedenen Stressbedingungen werden unter besonderer Berücksichtigung der Veränderungen des Lymphozyten- und Zytokinnetzwerks dargestellt und nach ihrer möglichen klinischen Bedeutung gewichtet. Praktische Konsequenzen für psychologische Interventionsstrategien werden zur Diskussion gestellt.

The Relationship between Psychological Stress and the Clinical Course of Multiple Sclerosis. An Update

The relationship between psychological stress and the course of MS has been investigated in several studies using methods with different qualities. The majority of findings indicates that acute short-term stressors have no negative consequences. Chronic psychosocial stressors, however, such as interpersonal conflicts, loss and complicated bereavement, low perceived social support, anxiety and depressive episodes have to be regarded as possible risk factors for the development of MS exacerbations. The neuroimmunological findings in MS and under various stress conditions are delineated with emphasis on the changes in lymphocyte and cytokine networks and evaluated with regard to their possible clinical significance. Practical consequences for psychological intervention strategies are discussed.

Key words

Multiple Sclerosis - Stress - Lymphocyte - Cytokine

Literatur

• 1 Ackerman K D, Martino M, Heyman R, Moyna N M, Rabin B S. Immunologic response to acute psychological stress in MS patients and controls.  J Neuroimmunol. 1996;  68 85-94
• 2 Andersen O, Lygner P E, Bergstrom T, Andersson M, Vahlne A. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study.  J Neurol. 1993;  240 417-422
• 3 Andersson P B, Waubant E, Goodkin D E. How should we proceed with disease-modifying treatments for multiple sclerosis?.  Lancet. 1997;  349 586-587
• 4 Baum A, Cohen L, Hall M. Control and intrusive memories as possible determinants of chronic stress.  Psychosom Med. 1993;  55 274-286
• 5 Baumgarten H G, Grozdanovic Z, Möller H J. Streßachse, Depression und Schlafstörungen. Die Rolle von Cortisol und von Serotonin.  Psychopharmakotherapie. 1997;  4 133-137
• 6 Bengtsson B O, Zhu J, Thorell L H, Olsson T, Link H, Walinder J. Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats.  J Neuroimmunol. 1992;  39 109-122
• 7 Biondi M, Picardi A. Clinical and biological aspects of bereavement and loss-induced depression: a reappraisal.  Psychother Psychosom. 1996;  65 229-245
• 8 Bremner J D. Acute and chronic responses to psychological trauma: where do we go from here?.  Am J Psychiat. 1999;  156 349-351
• 9 Brickner R M, Simons D J. Emotional stress in relation to attacks of multiple sclerosis.  Res Publ Ass Nerv Ment Dis. 1950;  28 143-149
• 10 Buelow J M. A correlational study of disabilities, stressors and coping methods in victims of multiple sclerosis.  J Neurosci Nurs. 1991;  23 247-252
• 11 Burchiel K J. Ectopic impulse generation in demyelinated axons: effects of PaCO₂, pH, and disodium edetate.  Ann Neurol. 1981;  9 378-383
• 12 Cohen S, Frank E, Doyle W J, Skoner D P, Rabin B S, Gwaltney J M. Types of stressors that increase susceptibility to the common cold in healthy adults.  Health Psychol. 1998;  17 214-223
• 13 Cohen S, Tyrrell D A, Smith A P. Psychological stress and susceptibility to the common cold.  New Engl J Med. 1991;  325 606-612
• 14 Cole S W, Kemeny M E, Taylor S E, Visscher B R, Fahey J L. Accelerated course of human immunodeficiency virus infection in gay men who conceal their homosexual identity.  Psychosom Med. 1996;  58 219-231
• 15 Comabella M, Balashov K, Issazadeh S, Smith D, Weiner H L, Khoury S J. Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy.  J Clin Invest. 1998;  102 671-678
• 16 Crawford J D, McIvor G P. Group psychotherapy: benefits in multiple sclerosis.  Arch Phys Med Rehab. 1985;  66 810-813
• 17 Crockard A D, Treacy M T, Droogan A G, McNeill T A, Hawkins S A. Transient immunomodulation by intravenous methylprednisolone treatment of multiple sclerosis.  Mult Scler. 1995;  1 20-24
• 18 Devins G M, Edworthy S M, Seland T P, Klein G M, Paul L C, Mandin H. Differences in illness intrusiveness across rheumatoid arthritis, end-stage renal disease, and multiple sclerosis.  J Nerv Ment Dis. 1993;  181 377-381
• 19 Elenkov I J, Papanicolaou D A, Wilder R L, Chrousos G P. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications.  Proc Assoc Am Phys. 1996;  108 374-381
• 20 Esterling B A, Kiecolt-Glaser J K, Glaser R. Psychosocial modulation of cytokine-induced natural killer cell activity in older adults.  Psychosom Med. 1996;  58 264-272
• 21 Fassbender K, Schmidt R, Mößner R, Kischka U, Kuhnen J, Schwartz A, Hennerici M. Mood disorders and dysfunction of hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation.  Arch Neurol. 1998;  55 66-72
• 22 Fawzy F I, Cousins N, Fawzy N W, Kemeny M E, Elashoff R, Morton D A. A structured psychiatric intervention for cancer patients. I. Changes over time in methods of coping and affective disturbance.  Arch Gen Psychiat. 1990;  47 720-725
• 23 Fawzy F I, Kemeny M E, Fawzy N W, Elashoff R, Morton D, Cousins N, Fahey J L. A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures.  Arch Gen Psychiat. 1990;  47 729-735
• 24 Feinstein A, O'Connor P, Gray T, Feinstein K. The effects of anxiety on psychiatric morbidity in patients with multiple sclerosis.  Mult Scler. 1999;  5 323-326
• 25 Foley F W, Bedell J R, LaRocca N G, Scheinberg L C, Reznikoff M. Efficacy of stress-inoculation training in coping with multiple sclerosis.  J Consult Clin Psychol. 1987;  55 919-922
• 26 Foley F W, Traugott U, LaRocca N G, Smith C R, Perlman K R, Caruso L S, Scheinberg L C. A prospective study of depression and immune dysregulation in multiple sclerosis.  Arch Neurol. 1992;  49 238-244
• 27 Folkman S, Lazarus R S. An analysis of coping in a middle-aged community sample.  J Health Soc Behav. 1980;  21 219-239
• 28 Franciotta D, Piccolo G, Zardini E, Bergamaschi R, Cosi V. Soluble CD8 and ICAM-1 in serum and CSF of MS patients treated with 6-methylprednisolone.  Acta Neurol Scand. 1997;  95 275-279
• 29 Gasperini C, Grasso M G, Fiorelli M, Millefiorini E, Morino S, Anzini A, Colleluori A, Salvetti M, Buttinelli C, Pozzilli C. A controlled study of potential risk factors preceding exacerbation in multiple sclerosis.  J Neurol Neurosurg Psychiat. 1995;  59 303-305
• 30 Gay D, Dick G, Upton G. Multiple sclerosis associated with sinusitis: case-controlled study in general practice.  Lancet. 1986;  (i) 815-819
• 31 Gayo A, Mozo L, Suárez A, Tuñón A, Lahoz C, Gutiérrez C. Interferon beta-1b treatment modulates TNFα and IFNγ spontaneous gene expression in MS.  Neurology. 1999;  52 1764-1770
• 32 George A, Schmidt C, Toyka K V, Sommer C. Serial determination of tumor necrosis factor-alpha content in rat sciatic nerve after chronic constriction injury.  Exp Neurol. 1999;  160 124-132
• 33 Gilchrist A C, Creed F H. Depression, cognitive impairment and social stress in multiple sclerosis.  J Psychosom Med. 1994;  38 193-201
• 34 Glaser R, Kiecolt-Glaser J K, Bonneau R H, Malarkey W, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine.  Psychosom Med. 1992;  54 22-29
• 35 Gollob J A, Schnipper C P, Murphy E A, Ritz J, Frank D A. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmenta-tion of STAT serine phosphorylation.  J Immunol. 1999;  162 4427-4481
• 36 Goodin D S, Ebers G C, Johnson K P, Rodriguez M, Sibley W A, Wolinsky J S. The relationship of MS to physical trauma and psychological stress. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.  Neurology. 1999;  52 1737-1745
• 37 Grant I, Brown G W, Harris T, McDonald W I, Patterson T, Trimble M R. Severely threatening events and marked life difficulties preceding onset or exacerbation of multiple sclerosis.  J Neurol Neurosurg Psychiat. 1989;  52 8-13
• 38 Grasser A, Möller A, Backmund H, Yassouridis A, Holsboer F. Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis.  Exp Clin Endocrinol Diab. 1996;  104 31-37
• 39 Guthrie T C, Nelson D A. Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.  J Neurol Sci. 1995;  129 1-8
• 40 Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis.  J Psychiat Res. 1999;  33 407-418
• 41 Hemmer B, Martin R. Neuroimmunologie und multiple Sklerose.  Akt Neurol. 1998;  25 83-95
• 42 Herbert T B, Cohen S. Stress and immunity in humans: a meta-analytic review.  Psychosom Med. 1993;  55 364-379
• 43 Hohlfeld R. Multiple Sklerose.  Akt Neurol. 1995;  22 125-130
• 44 Inman W S. Can emotional conflict induce disseminated sclerosis?.  Brit J Med Psychol. 1948;  21 135-154
• 45 Ironson G, Friedman A, Klimas N. Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus.  Int J Behav Med. 1994;  1 90-105
• 46 Ironson G, Wynings C, Schneiderman N, Baum A, Rodriguez M, Greenwood D, Benight C, Antoni M, LaPerriere A, Huang H S, Klimas N, Fletcher M A. Posttraumatic stress symptoms, intrusive thoughts, loss, and immune function after Hurricane Andrew.  Psychosom Med. 1997;  59 128-141
• 47 Irwin M, Daniels M, Bloom E T, Smith T L, Weiner H. Life events, depressive symptoms, and immune function.  Am J Psychiat. 1987;  144 437-441
• 48 Issazadeh S, Lorentzen J C, Mustafa M I, Hojeberg B, Mussener A, Olsson T. Cytokines in relapsing experimental autoimmune encephalomyelitis in DA rats: persistent mRNA expression of proinflammatory cytokines and absent expression of interleukin-10 and transforming growth factor-beta.  J Neuroimmunol. 1996;  69 103-115
• 49 Jean V M, Paul R H, Beatty W W. Psychological and neuropsychological predictors of coping patterns by patients with multiple sclerosis.  J Clin Psychol. 1999;  55 21-26
• 50 Kagan B L, Baldwin R L, Munoz D, Wisnieski B J. Formation of ion-permeable channels by tumor necrosis factor-alpha.  Science. 1992;  255 1427-1430
• 51 Karp C L. Interleukin-12: Amiss in MS.  Ann Neurol. 1999;  45 689-692
• 52 Karussis D M, Abramsky O. Immunomodulating therapeutic approaches for multiple sclerosis.  J Neurol Sci. 1998;  153 239-250
• 53 Kiecolt-Glaser J K, Fisher L D, Ogrocki P, Stout J C, Speicher C, Glaser R. Marital quality, marital disruption, and immune function.  Psychosom Med. 1987;  49 13-34
• 54 Kiecolt-Glaser J K, Garner W, Speicher C, Penn G M, Holliday J, Glaser R. Psychosocial modifiers of immunocompetence in medical students.  Psychosom Med. 1984;  46 7-14
• 55 Kiecolt-Glaser J K, Glaser R. Psychoneuroimmunology: can psychological interventions modulate immunity?.  J Consult Clin Psychol. 1992;  60 569-575
• 56 Kiecolt-Glaser J K, Jason R D, Speicher C E, Trask O J, Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health.  Psychosom Med. 1991;  53 345-362
• 57 Kiecolt-Glaser J K, Malarkey W B, Chee M A, Newton T, Cacioppo J T, Mao H Y, Glaser R. Negative behavior during marital conflict is associated with immunological down-regulation.  Psychosom Med. 1993;  55 395-409
• 58 Koh K B. Emotion and immunity.  J Psychosom Res. 1998;  45 107-115
• 59 Landmann R, Schaub B, Link S, Wacker H R. Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy.  Biol Psychiat. 1997;  41 675-681
• 60 Larcombe N A, Wilson P H. An evaluation of cognitive-behaviour therapy for depression in patients with multiple sclerosis.  Brit J Psychiat. 1984;  145 366-371
• 61 La Via M F, Munno I, Lydiard R B, Workman E W, Hubbard J R, Michel Y, Paulling E. The influence of stress intrusion on immunodepression in generalized anxiety disorder patients and controls.  Psychosom Med. 1996;  58 138-142
• 62 Leonard J P, Waldburger K E, Schaub R G, Smith T, Hewson A K, Cuzner M L, Goldman S J. Regulation of the inflammatory response in animal models of multiple sclerosis by interleukin-12.  Crit Rev Immunol. 1997;  17 545-553
• 63 Leventhal H, Patrick-Miller L, Leventhal E A. It's long-term stressors that take a toll: comment on Cohen et al. (1998).  Health Psychol. 1998;  17 211-213
• 64 Levy S, Herberman R, Lippman M, d'Angelo T. Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer.  J Clin Oncol. 1987;  5 348-353
• 65 Levy S M, Herberman R B, Whiteside T, Sanzo K, Lee J, Kirkwood J. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients.  Psychosom Med. 1990;  52 73-85
• 66 Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression.  Cytokine. 1997;  9 853-858
• 67 Maes M, Scharpe S, Meltzer H Y, Okayli G, Bosmans E, D'Hondt P, Vanden Bossche B V, Cosyns P. Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response.  Psychiat Res. 1994;  54 143-160
• 68 Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpe S, Smith R S. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety.  Cytokine. 1998;  10 313-318
• 69 Marshall G D, Agarwal S K, Lloyd C, Cohen L, Henninger E M, Morris G J. Cytokine dysregulation associated with exam stress in healthy medical students.  Brain Behav Immun. 1998;  12 297-307
• 70 Martin R, McFarland H F. Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis.  Crit Rev Clin Lab Sci. 1995;  32 121-182
• 71 Martino G, Brambilla E, Filippi M, Martinelli V, Colombo B, Rodegher M, Comi G, Grimaldi L M. Interferon-gamma activated calcium influx in peripheral blood lymphocytes from patients with primary and secondary progressive multiple sclerosis.  J Neurol Neurosurg Psychiat. 1996;  61 515-517
• 72 McEwen B S. Protective and damaging effects of stress mediators.  New Engl J Med. 1998;  338 171-179
• 73 McFarland H F. The path to damage in multiple sclerosis.  Ann Neurol. 1999;  46 141-142
• 74 Mei-Tal V, Meyerowitz S, Engel G L. The role of psychological process in a somatic disorder: multiple sclerosis. 1. The emotional setting of illness onset and exacerbation.  Psychosom Med. 1970;  32 67-86
• 75 Michelson D, Stone L, Galliven E, Magiakou M A, Chrousos G P, Sternberg E M, Gold P W. Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function.  J Clin Endocrinol Metab. 1994;  79 848-853
• 76 Miller A, Shapiro S, Gershtein R, Kinarty A, Rawashdeh H, Honigman S, Lahat N. Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation.  J Neuroimmunol. 1998;  92 113-121
• 77 Mohr D C, Goodkin D E, Likosky W, Gatto N, Baumann K A, Rudick R A. Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis.  Arch Neurol. 1997;  54 531-533
• 78 Mohr D C, Goodkin D E, Likosky W, Gatto N, Neilley L K, Griffin C, Stiebling B. Therapeutic expectations of patients with multiple sclerosis upon initiating interferon beta-1b: relationship to adherence to treatment.  Mult Scler. 1996;  2 222-226
• 79 Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis.  Brain. 1996;  119 225-237
• 80  MS-Therapie Konsensus Gruppe (MSTKG). Immunmodulatorische Stufentherapie der multiplen Sklerose.  Nervenarzt. 1999;  70 371-386
• 81 Müller N. Die Rolle des Zytokinnetzwerks im ZNS und psychische Störungen.  Nervenarzt. 1997;  68 11-20
• 82 Muthny F A, Bechtel M, Spaete M. Laienätiologie und Krankheitsverarbeitung bei schweren körperlichen Erkrankungen. Eine empirische Vergleichsstudie mit Herzinfarkt-, Krebs-, Dialyse- und MS-Patientinnen.  Psychother Psychosom med Psychol. 1992;  42 41-53
• 83 Naliboff B D, Benton D, Solomon G F, Morley J E, Fahey J L, Bloom E T, Makinodan T, Gilmore S L. Immunological changes in young and old adults during brief laboratory stress.  Psychosom Med. 1991;  53 121-132
• 84 Nicoletti F, Patti F, Cocuzza C, Zaccone P, Nicoletti A, Di Marco R, Reggio A. Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis.  J Neuroimmunol. 1996;  70 87-90
• 85 Nisipeanu P, Korczyn A D. Psychological stress as risk factor for exacerbations in multiple sclerosis.  Neurology. 1993;  43 1311-1312
• 86 Noy S, Achiron A, Gabbay U, Barak Y, Rotstein Z, Laor N, Sarova-Pinhas I. A new approach to affective symptoms in relapsing-remitting multiple sclerosis.  Compr Psychiat. 1995;  36 390-395
• 87 O'Connor P, Detsky A S, Tansey C, Kucharczyk W. Effect of diagnostic testing for multiple sclerosis on patient health perceptions.  Arch Neurol. 1994;  51 46-51
• 88 Ostrow D G. Editorial: The search for the elusive psychosocial modulators of human immunodeficiency virus disease progression.  Psychosom Med. 1996;  58 232-233
• 89 Ozenci V, Kouwenhoven M, Huang Y M, Xiao B, Kivisakk P, Fredrikson S, Link H. Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment.  Scand J Immunol. 1999;  49 554-561
• 90 Panitch H S. Influence of infection on exacerbations of multiple sclerosis.  Ann Neurol. 1994;  36, Suppl S25-S28
• 91 Panitch H S, Hirsch R L, Schindler J, Johnson K P. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system.  Neurology. 1987;  37 1097-1102
• 92 Philippopoulos G S, Wittkower E D, Cousineau A. The etiologic significance of emotional factors in onset and exacerbations of multiple sclerosis. A preliminary report.  Psychosom Med. 1958;  20 458-474
• 93 Poser C M. Trauma, stress, and multiple sclerosis. Bull Am Acad Psychiat Law 1980 Vol VII, No 3
• 94 Purba J S, Raadsheer F C, Hofman M A, Ravid R, Polman C H, Kamp-horst W, Swaab D F. Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.  Neuroendocrinology. 1995;  62 62-70
• 95 Rabins P V, Brooks B R, O'Donnell P, Pearlson G D, Moberg P, Jubelt B, Coyle P, Dalos N, Folstein M F. Structural brain correlates of emotional disorder in multiple sclerosis.  Brain. 1986;  109 585-597
• 96 Rep M H, Schrijver H M, van Lopik T, Hintzen R Q, Roos M T, Ader H J, Polman C H, van Lier R A. Interferon (IFN)-beta treatment enhances CD95 and interleukin 10 expression but reduces interferon-gamma producing T cells in MS patients.  J Neuroimmunol. 1999;  96 92-100
• 97 Rieckmann P, Albrecht M, Kitze B, Weber T, Tumani H, Broocks A, Luer W, Helwig A, Poser S. Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity.  Ann Neurol. 1995;  37 82-88
• 98 Riether A M. Anxiety in patients with multiple sclerosis. Semin.  Clin Neuropsychiat. 1999;  4 103-113
• 99 Roos R A, Wintzen A R, Vielvoye G, Polder T W. Paroxysmal kinesigenic choreoathetosis as presenting symptom of multiple sclerosis.  J Neurol Neurosurg Psychiat. 1991;  54 657-658
• 100 Schubert D S, Foliart R H. Increased depression in multiple sclerosis patients. A meta-analysis.  Psychosomatics. 1993;  34 124-130
• 101 Schwartz C E. Teaching coping skills enhances quality of life more than peer support: results of a randomized trial with multiple sclerosis patients.  Health Psychol. 1999;  18 211-220
• 102 Selmaj K, Raine C S, Farooq M, Norton W T, Brosnan N F. Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin.  J Immunol. 1991;  147 1522-1529
• 103 Sharief M K, Hentges R. Association between tumor necrosis factor-a and disease progression in chronic progressive multiple sclerosis.  New Engl J Med. 1991;  325 467-472
• 104 Shrikant P, Weber E, Jilling T, Benveniste E N. Intercellular adhession molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6.  J Immunol. 1995;  155 1489-1501
• 105 Sibley W A. Risk factors in multiple sclerosis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. London; Chapman & Hall 1997: 141-148
• 106 Sibley W A, Bamford C R, Clark K. Clinical viral infections and multiple sclerosis. Lancet 1985; i: 1313-1315
• 107 Sorkin L S, Xiao W H, Wagner R, Myers R R. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibers.  Neuroscience. 1997;  81 255-262
• 108 Sriram S, Stratton C W, Yao S, Tharp A, Ding L, Bannan J D, Mitchell W M. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis.  Ann Neurol. 1999;  46 6-14
• 109 Stenager E, Knudsen L, Jensen K. Multiple sclerosis: correlation of anxiety, physical impairment and cognitive dysfunction.  Ital J Neurol Sci. 1994;  15 97-101
• 110 Stenager E N, Stenager E, Koch-Henriksen N, Brönnum-Hansen H, Hyllested K, Jensen K, Bille-Brahe U. Suicide and multiple sclerosis: an epidemiological investigation.  J Neurol Neurosurg Psychiat. 1992;  55 542-545
• 111 Sullivan M J, Edgley K, Mikail S, Dehoux E, Fisher R. Psychological correlates of health care utilization in chronic illness.  Can J Rehab. 1992;  6 13-21
• 112 Then Bergh F, Grasser A, Trenkwalder C, Backmund H, Holsboer F, Rupprecht . Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis.  J Neurol. 1999;  246 292-298
• 113 Tselis A C, Lisak R P. Multiple sclerosis. Therapeutic update.  Arch Neurol. 1999;  56 277-280
• 114 Van Boxel-Dezaire A H, Hoff S C, van Oosten B W, Verweij C L, Dräger A M, Adér H J, van Houwelingen J C, Barkhof F, Polman C H, Nagelkerken L. Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis.  Ann Neurol. 1999;  45 695-703
• 115 Wandinger K P, Wessel K, Trillenberg P, Heindl N, Kirchner H. Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients.  Acta Neurol Scand. 1998;  97 359-365
• 116 Warren S, Greenhill S, Warren K G. Emotional stress and the development of multiple sclerosis: case-control evidence of a relationship.  J Chron Dis. 1982;  35 821-831
• 117 Warren S, Warren K G, Cockerill R. Emotional stress and coping in multiple sclerosis (MS) and exacerbations.  J Psychosom Res. 1991;  35 37-47
• 118 Wei T, Lightman S L. The neuroendocrine axis in patients with multiple sclerosis.  Brain. 1997;  120 1067-1076
• 119 Winterholler M, Erbguth F, Neundörfer B. Verwendung paramedizinischer Verfahren durch MS-Patienten - Patientencharakterisierung und Anwendungsgewohnheiten.  Fortschr Neurol Psychiat. 1997;  65 555-561
• 120 Wisniewski H M, Keith A B. Chronic relapsing experimental allergic encephalomyelitis. An experimental model of multiple sclerosis.  Ann Neurol. 1977;  1 144-149
• 121 Woiciechowsky C, Asadullah K, Nestler D, Eberhardt D, Platzer C, Schoning B, Glockner F, Lanksch W R, Volk H D, Docke W D. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury.  Nat Med. 1998;  4 808-813
• 122 Xia Z, DePierre J W, Nassberger L. Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells.  Immunopharmacology. 1996;  34 27-37
• 123 Yehuda R, Southwick S M, Krystal J H, Bremner D, Charney D S, Mason J W. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder.  Am J Psychiat. 1993;  150 83-86
• 124 Yehuda R, Teicher M H, Trestman R L, Levengood R A, Siever L J. Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.  Biol Psychiat. 1996;  40 79-88