Alexithymie bei Multipler Sklerose – eine narrative Übersicht

Zusammenfassung

Alexithymie ist ein multidimensionales Konstrukt der Persönlichkeit, welches durch ein nach außen hin orientiertes Denken sowie Schwierigkeiten bei der Gefühlsbeschreibung und -identifizierung einer anderen Person gekennzeichnet ist. Obwohl sie bei psychiatrischen Patienten gut beschrieben ist, wurde ihr Vorkommen und die Pathophysiologie im Zusammenhang mit der Multiplen Sklerose (MS) erst neuerdings untersucht. In dieser narrativen Übersichtsarbeit sollen Prävalenzen, Ursachen, neurobiologische und klinische Befunde dargestellt werden. Die Prävalenz der Alexithymie in MS reicht von 10 bis 53%. Es scheint Assoziationen mit Angststörungen, Depressionen, Fatigue und einigen kognitiven Aspekten zu geben. Die Beziehung zu klinischen und klassischen kognitiven Variablen/Kriterien ist bislang wenig untersucht. Schlussendlich stellt eine Arbeit einen pathophysiologischen Bezug dar und diskutiert eine aberrante interhemisphärische Übertragung. Zusammenfassend zeigt die Alexithymie bei MS eine negative Auswirkung auf die Lebensqualität, deshalb stellt das Screening nach ihr einen wichtigen Punkt im Krankheitsmanagement dar. Ihre Beziehung zu klinischen, emotionalen und kognitiven Kofaktoren bedarf weiterer Untersuchungen. Größer angelegte Studien inklusive bildgebender Verfahren sind dringend notwendig, um ein besseres Verständnis für die neuronalen Mechanismen der Alexithymie bei MS zu gewinnen.

Abstract

Alexithymia is a multidimensional construct of personality implicating difficulties in identifying and describing another’s feelings, and externally oriented thinking. It is broadly reported in psychiatric patients but has gained little attention regarding its occurrence and pathophysiology in multiple sclerosis (MS). This narrative review aims to address prevalence, etiology, neurobiological, and clinical findings of alexithymia. The prevalence of alexithymia in MS ranges from 10 to 53%. There seems to be an association with anxiety, depression, fatigue, and some aspects of social cognition, while the relationship with clinical and classical cognitive variables was rarely evaluated. Only a few studies referred to its pathophysiology assuming an aberrant interhemispheric transfer or regional cerebral abnormalities. The prevalence of alexithymia in MS and the potential negative impact on quality of life and interpersonal communication could severely impact clinical MS management and a screnning for these factors should be mandatory. Thus, further evaluation is needed concerning its relationship with clinical, emotional, and cognitive confounders. Large-scale studies employing neuroimaging techniques are needed for a better understanding of the neural underpinnings of this MS feature.

Schlüsselwörter

Alexithymie - Multiple Sklerose - Emotionsverarbeitung - Emotionswahrnehmung

Key words

alexithymia - multiple sclerosis - emotional processing - emotional awareness

Publication History

Received: 14 February 2020

Accepted: 14 June 2022

Article published online:
10 August 2022

• Literatur

• 1 Pelletier J, Benoit N, Montreuil M, Habib M. Cognitive and emotional disorders in multiple sclerosis. Can a suitable management strategy be envisaged?. Pathol Biol 2000; 48: 121-131
• 2 Chalah MA, Ayache SS. Psychiatric event in multiple sclerosis: Could it be the tip of the iceberg?. Rev Bras Psiquiatr 2017; 39: 365-368
• 3 Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41: 685-691
• 4 Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 1991; 41: 692-696
• 5 Benedict R, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N. et al. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc 2006; 12: 549-558
• 6 Sanfilipo MP, Benedict RHB, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 2006; 66: 685-692
• 7 Ayache SS, Chalah MA. Cortical excitability changes: A mirror to the natural history of multiple sclerosis?. Neurophysiol Clin 2017; 47: 221-223
• 8 Mohr DC, Cox D. Multiple sclerosis: Empirical literature for the clinical health psychologist. J Clin Psychol 2001; 57: 479-499
• 9 Ayache SS, Palm U, Chalah MA, Nguyen R, Farhat WH, Créange A. et al. Orienting network dysfunction in progressive multiple sclerosis. J Neurol Sci 2015; 351: 206-207
• 10 Van Schependom J, D’Hooghe MB, Cleynhens K, D’Hooge M, Haelewyck MC, De Keyser J. et al. Reduced information processing speed as primum movens for cognitive decline in MS. Mult Scler J 2015; 21: 83-91
• 11 Chalah MA, Ayache SS. Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis. J Int Neuropsychol Soc 2017; 23: 266-286
• 12 Cacioppo JT, Decety J. Social neuroscience: Challenges and opportunities in the study of complex behavior. Ann N Y Acad Sci 2011; 1224: 162-173
• 13 Bird G, Cook R. Mixed emotions: The contribution of alexithymia to the emotional symptoms of autism. Transl Psychiatry 23; 3: e285
• 14 Conrad R, Wegener I, Imbierowicz K, Liedtke R, Geiser F. Alexithymia, temperament and character as predictors of psychopathology in patients with major depression. Psychiatry Res 2009; 165: 137-144
• 15 Luminet O. Commentary on the paper “Is alexithymia a risk factor for major depression, personality disorder, or alcohol use disorders?” A prospective population-based study. J Psychosom Res 2010; 68: 275-277
• 16 Ayache SS, Chalah MA, Kuempfel T, Padberg F, Lefaucheur JP, Palm U. Emotionserkennung, Theory of Mind und Empathie bei Multipler Sklerose. Fortschr Neurol Psychiatr 2017; 85: 663-674
• 17 Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry 2003; 54: 504-514
• 18 Gross JJ. Antecedent- and Response-Focused Emotion Regulation: Divergent Consequences for Experience, Expression, and Physiology. J Pers Soc Psychol 1998; 74: 224-237
• 19 Roedema TM, Simons RF. Emotion-processing deficit in alexithymia. Psychophysiology 1999; 36: 379-387
• 20 Mueller J, Alpers GW, Reim N. Dissociation of rated emotional valence and Stroop interference in observer-rated alexithymia. J Psychosom Res 2006; 61: 261-269
• 21 Swart M, Kortekaas R, Aleman A. Dealing with feelings: Characterization of trait Alexithymia on emotion regulation strategies and cognitive-emotional processing. PLoS One 2009; 4: e5751
• 22 Grynberg D, Chang B, Corneille O, Maurage P, Vermeulen N, Berthoz S. et al. Alexithymia and the processing of emotional facial expressions (EFEs): Systematic review, unanswered questions and further perspectives. PLoS One 2012; 7: e42429
• 23 Bermond B, Bierman DJ, Cladder MA, Moormann PP, Vorst HCM. The cognitive and affective alexithymia dimensions in the regulation of sympathetic responses. Int J Psychophysiol 2010; 75: 227-233
• 24 Van der Velde J, Van Tol MJ, Goerlich-Dobre KS, Gromann PM, Swart M, De Haan L. et al. Dissociable morphometric profiles of the affective and cognitive dimensions of alexithymia. Cortex 2014; 54: 190-199
• 25 Parker JDA, Keightley ML, Smith CT, Taylor GJ. Interhemispheric transfer deficit in alexithymia: An experimental study. Psychosom Med 1999; 61: 464-468
• 26 Taylor GJ, Bagby RM. New Trends in Alexithymia Research. Psychother Psychosom 2004; 73: 68-77
• 27 Walker S, O’Connor DB, Schaefer A. Brain potentials to emotional pictures are modulated by alexithymia during emotion regulation. Cogn Affect Behav Neurosci 2011; 11: 463-475
• 28 Pollatos O, Gramann K. Attenuated modulation of brain activity accompanies emotion regulation deficits in alexithymia. Psychophysiology 2012; 49: 651-658
• 29 Venta A, Hart J, Sharp C. The relation between experiential avoidance, alexithymia and emotion regulation in inpatient adolescents. Clin Child Psychol Psychiatry 2013; 18: 398-410
• 30 Chalah MA, Riachi N, Ahdab R, Créange A, Lefaucheur J-P, Ayache SS. Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation. Front Cell Neurosci 2015; 9: 460
• 31 Bermond B, Vorst HCM, Moormann PP. Cognitive neuropsychology of alexithymia: Implications for personality typology. Cogn. Neuropsychiatry 2006; 11: 332-360
• 32 Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S. et al. Functional atlas of emotional faces processing: A voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 2009; 34: 418-432
• 33 Van der Velde J, Servaas MN, Goerlich KS, Bruggeman R, Horton P, Costafreda SG. et al. Neural correlates of alexithymia: A meta-analysis of emotion processing studies. Neurosci Biobehav Rev 2013; 37: 1774-1785
• 34 Vuilleumier P. How brains beware: Neural mechanisms of emotional attention. Trends Cogn Sci 2005; 9: 585-594
• 35 Jacob H, Kreifelts B, Brück C, Erb M, Hösl F, Wildgruber D. Cerebral integration of verbal and nonverbal emotional cues: Impact of individual nonverbal dominance. Neuroimage 2012; 61: 738-747
• 36 Critchley HD, Wiens S, Rotshtein P, Öhman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci 2004; 7: 189-195
• 37 Tsuchiya N, Adolphs R. Emotion and consciousness. Trends Cogn Sci 2007; 11: 158-167
• 38 Terasawa Y, Fukushima H, Umeda S. How does interoceptive awareness interact with the subjective experience of emotion? An fMRI Study. Hum Brain Mapp 2013; 34: 598-612
• 39 Adolphs R. Recognizing emotion from facial expressions: psychological and neurological mechanisms. Behav Cogn Neurosci Rev 2002; 1: 21-62
• 40 Adolphs R. Neural systems for recognizing emotion. Curr Opin Neurobiol 2002; 12: 169-177
• 41 Kandel EJ, Schwartz J, Jessel TM. (eds). Principles of Neural Science. London: Prentice-Hall; 1991
• 42 Salloway SP, Malloy PF, Duffy JD. The frontal lobes and neuropsychiatric illness. J Neuropsychiatry Clin Neurosci 1994; 6: 341-477
• 43 Alexander GE, Crutcher MD, Delong MR. Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” & “limbic” functions. Prog Brain Res 1990; 85: 119-147
• 44 Wingbermühle E, Theunissen H, Verhoeven WMA, Kessels RPC, Egger JIM. The neurocognition of alexithymia: Evidence from neuropsychological and neuroimaging studies. Acta Neuropsychiatr 2012; 24: 67-80
• 45 Moriguchi Y, Komaki G. Neuroimaging studies of alexithymia: Physical, affective, and social perspectives. Biopsychosoc Med 2013; 7: 8
• 46 Larsen JK, Brand N, Bermond B, Hijman R. Cognitive and emotional characteristics of alexithymia: A review of neurobiological studies. J Psychosom Res 2003; 54: 533-541
• 47 Bermond B, Bleys JW, Stoffels EJ. Left hemispheric preference and alexithymia: A neuropsychological investigation. Cogn Emot 2005; 19: 151-160
• 48 McClelland JL, Rumelhart DE, Hinton GE. Une nouvelle approche de la cognition : le connexionnisme. Debat 1987; 47: 45-64
• 49 Gazzaniga MS. Organization of the human brain. Science 1989; 245: 947-952
• 50 Kolb B, Wishaw IQ. (eds). Fundamentals of human neuropsychology. New York: Worth; 1990
• 51 Tucker DM. Lateral brain function, emotion, and conceptualization. Psychol Bull 1981; 89: 19-46
• 52 Hoppe KD. Hemispheric specialization and creativity. Psychiatr Clin North Am 1988; 11: 303-315
• 53 Gainotti G, Caltagirone C, Zoccolotti P. Left/right and cortical/subcortical dichotomies in the neuropsychological study of human emotions. Cogn Emot 1993; 7: 71-93
• 54 Bear DM. Hemispheric Specialization and the Neurology of Emotion. Arch Neurol 1983; 40: 195-202
• 55 Gazzaniga MS, LeDoux J. (eds). The integrated mind. New York: Plenum Press; 1978
• 56 Parker JDA, Taylor GJ, Michael Bagby R. Alexithymia and the recognition of facial expressions of emotion. Psychother Psychosom 1993; 59: 197-202
• 57 Jessimer M, Markham R. Alexithymia: A right hemisphere dysfunction specific to recognition of certain facial expressions?. Brain Cogn 1997; 34: 246-258
• 58 Hoppe KD, Bogen JE. Alexithymia in twelve commissurotomized patients. Psychother Psychosom 1977; 28: 148-155
• 59 TenHouten WD, Hoppe KD, Bogen JE, Walter DO. Alexithymia and the split brain. I. Lexical-level content analysis. Psychother Psychosom 1985; 43: 202-208
• 60 Houtveen JH, Bermond B, Elton MR. Alexithymia: A disruption in a cortical network? An EEG power and coherence analysis. J Psychophysiol 1997; 11: 147-157
• 61 Ross ED. Right hemisphere’s role in language, affective behavior and emotion. Trends Neurosci 1984; 7: 342-346
• 62 Borod JC. Interhemispheric and Intrahemispheric Control of Emotion: A Focus on Unilateral Brain Damage. J Consult Clin Psychol 1992; 60: 339-348
• 63 Borod JC, Obler LK, Erhan HM, Grunwald IS, Cicero BA, Welkowitz J. et al. Right hemisphere emotional perception: Evidence across multiple channels. Neuropsychology 1998; 12: 446-458
• 64 Mandal MK, Borod JC, Asthana HS, Mohanty A, Mohanty S, Koff E. Effects of lesion variables and emotion type on the perception of facial emotion. J Nerv Ment Dis 1999; 187: 603-609
• 65 Borod JC, Andelman F, Obler LK, Tweedy JR, Wilkowitz J. Right hemisphere specialization for the identification of emotional words and sentences: Evidence from stroke patients. Neuropsychologia 1992; 30: 827-844
• 66 Bermond B. Brain and alexithymia. In: Vingerhoets A, van Bussen F, Boelhouwers J, editors. The (non) Expression of Emotion in Health and Disease. Tilburg: Tilburg University Press; 1997
• 67 Zeitlin SB, Lane RDS, O’Leary D, Schrift MJ. Interhemispheric transfer deficit and alexithymia. Am J Psychiatry 1989; 146: 1434-1439
• 68 Dewaraja R, Sasaki Y. A left to right hemisphere callosal transfer deficit of nonlinguistic information in alexithymia. Psychother Psychosom 1990; 54: 201-207
• 69 Neafsey EJ. Prefrontal cortical control of the autonomic nervous system: Anatomical and physiological observations. Prog Brain Res 1991; 85: 147-166
• 70 Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behaviour. Brain 1995; 118: 279-306
• 71 Lane RD, Ahern GL, Schwartz GE, Kaszniak AW. Is alexithymia the emotional equivalent of blindsight?. Biol Psychiatry 1997; 42: 834-844
• 72 Milad MR, Quirk GJ, Pitman RK, Orr SP, Fischl B, Rauch SL. A Role for the Human Dorsal Anterior Cingulate Cortex in Fear Expression. Biol Psychiatry 2007; 62: 1191-1194
• 73 Gündel H, López-Sala A, Ceballos-Baumann AO, Deus J, Cardoner N, Marten-Mittag B. et al. Alexithymia Correlates with the Size of the Right Anterior Cingulate. Psychosom Med 2004; 66: 132-140
• 74 Paradiso S, Vaidya JG, McCormick LM, Jones A, Robinson RG. Aging and alexithymia: Association with reduced right rostral cingulate volume. Am J Geriatr Psychiatry 2008; 16: 760-769
• 75 Borsci G, Boccardi M, Rossi R, Rossi G, Perez J, Bonetti M. et al. Alexithymia in healthy women: A brain morphology study. J Affect Disord 2009; 14: 208-215
• 76 Sturm VE, Levenson RW. Alexithymia in neurodegenerative disease. Neurocase 2011; 17: 242-250
• 77 Ihme K, Dannlowski U, Lichev V, Stuhrmann A, Grotegerd D, Rosenberg N. et al. Alexithymia is related to differences in gray matter volume: A voxel-based morphometry study. Brain Res 2013; 1491: 60-67
• 78 Grabe HJ, Wittfeld K, Hegenscheid K, Hosten N, Lotze M, Janowitz D. et al. Alexithymia and brain gray matter volumes in a general population sample. Hum Brain Mapp 2014; 35: 5932-5945
• 79 Koven NS, Roth RM, Garlinghouse MA, Flashman LA, Saykin AJ. Regional gray matter correlates of perceived emotional intelligence. Soc Cogn Affect Neurosci 2011; 6: 582-590
• 80 Heinzel A, Minnerop M, Schäfer R, Müller HW, Franz M, Hautzel H. Alexithymia in healthy young men: A voxel-based morphometric study. J Affect Disord 2012; 136: 1252-1256
• 81 Kubota M, Miyata J, Hirao K, Fujiwara H, Kawada R, Fujimoto S. et al. Alexithymia and regional gray matter alterations in schizophrenia. Neurosci Res 2011; 70: 206-213
• 82 Zhang X, Salmeron BJ, Ross TJ, Geng X, Yang Y, Stein EA. Factors underlying prefrontal and insula structural alterations in smokers. Neuroimage 2011; 54: 42-48
• 83 Goerlich-Dobre KS, Bruce L, Martens S, Aleman A, Hooker CI. Distinct associations of insula and cingulate volume with the cognitive and affective dimensions of alexithymia. Neuropsychologia 2014; 53: 284-292
• 84 Pouga L, Berthoz S, De Gelder B, Grèzes J. Individual differences in socioaffective skills influence the neural bases of fear processing: The case of alexithymia. Hum Brain Mapp 2010; 31: 1469-1481
• 85 Koch K, Wagner G, Schachtzabel C, Peikert G, Schultz CC, Sauer H. et al. Aberrant anterior cingulate activation in obsessive-compulsive disorder is related to task complexity. Neuropsychologia 2012; 50: 958-964
• 86 Mulert C, Menzinger E, Leicht G, Pogarell O, Hegerl U. Evidence for a close relationship between conscious effort and anterior cingulate cortex activity. Int J Psychophysiol 2005; 56: 65-80
• 87 Goerlich KS, Aleman A, Martens S. The Sound of Feelings: Electrophysiological Responses to Emotional Speech in Alexithymia. PLoS One 2012; 7: e36951
• 88 Singer T, Critchley HD, Preuschoff K. A common role of insula in feelings, empathy and uncertainty. Trends Cogn Sci 2009; 13: 334-340
• 89 Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci 2011; 15: 85-93
• 90 Kano M, Fukudo S, Gyoba J, Kamachi M, Tagawa M, Mochizuki H. et al. Specific brain processing of facial expressions in people with alexithymia: An H215O-PET study. Brain 2003; 126: 1474-1484
• 91 Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 4: 215-222
• 92 Amaral DG, Price JL, Pitkanen A, Carmichael ST. Anatomical organization of the primate amygdaloid complex. In: Goldstein L (eds). The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. Yale: Yale J Biol Med; 1992
• 93 Giuliani NR, Drabant EM, Gross JJ. Anterior cingulate cortex volume and emotion regulation: Is bigger better?. Biol Psychol 2011; 86: 379-382
• 94 Uher T. Alexithymia and immune dysregulation: A critical review. Act Nerv Super (Praha) 2010; 52: 40-44
• 95 Guilbaud O, Corcos M, Hjalmarsson L, Loas G, Jeammet P. Is there a psychoneuroimmunological pathway between alexithymia and immunity? Immune and physiological correlates of alexithymia. Biomed Pharmacother 2003; 57: 292-295
• 96 De Berardis D, Conti C, Iasevoli F, Valchera A, Fornaro M, Cavuto M. et al. Alexithymia and its relationships with acute phase proteins and cytokine release: an updated review. J Biol Regul Homeost Agents 2014; 28: 795-799
• 97 Uher T, Bob P. Cerebrospinal fluid IL-8 levels reflect symptoms of alexithymia in patients with non-inflammatory neurological disorders. Psychoneuroendocrinology 2011; 36: 1148-1153
• 98 Bruni R, Serino FM, Galluzzo S, Coppolino G, Cacciapaglia F, Vadacca M. et al. Alexithymia and neuroendocrine-immune response in patients with autoimmune diseases: Preliminary results on relationship between alexithymic construct and TNF-α levels. Ann N Y Acad Sci 2006; 1069: 208-211
• 99 Vadacca M, Bruni R, Caccipaglia F, Serino F, Arcarese L, Buzzulini F. et al. Alexithymia and immunoendocrine parameters in patients affected by systemic lupus erythematosus and rheumatoid arthritis. Reumatismo 2008; 60: 50-56
• 100 Bossu P, Salani F, Cacciari C, Picchetto L, Cao M, Bizzoni F. et al. Disease Outcome, Alexithymia and Depression are Differently Associated with Serum IL-18 Levels in Acute Stroke. Curr Neurovasc Res 2009; 6: 163-170
• 101 Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Prog Neurobiol 2005; 76: 77-98
• 102 Kawanokuchi J, Mizuno T, Takeuchi H, Kato H, Wang J, Mitsuma N. et al. Production of interferon-γ by microglia. Mult Scler 2006; 12: 558-564
• 103 Muzio L, Martino G, Furlan R. Multifaceted aspects of inflammation in multiple sclerosis: The role of microglia. J Neuroimmunol 2007; 191: 39-44
• 104 Chalah MA, Riachi N, Ahdab R, Créange A, Lefaucheur JP, Ayache SS. Fatigue in multiple sclerosis: Neural correlates and the role of non-invasive brain stimulation. Front Cell Neurosci 2015; 9: 460
• 105 Ayache SS, Chalah MA. Fatigue in multiple sclerosis – Insights into evaluation and management. Neurophysiol Clin 2017; 47: 139-117
• 106 Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α. J Neurosci 2005; 25: 3219-3228
• 107 Lai AY, Swayze RD, El-Husseini A, Song C. Interleukin-1 beta modulates AMPA receptor expression and phosphorylation in hippocampal neurons. J Neuroimmunol 2006; 175: 97-106
• 108 Mizuno T, Zhang G, Takeuchi H, Kawanokuchi J, Wang J, Sonobe Y. et al. Interferon-γ directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-γ receptor and AMPA GluR1 receptor. FASEB J 2008; 22: 1797-1806
• 109 Ham BJ, Lee MS, Lee YM, Kim MK, Choi MJ, Oh KS. et al. Association between the catechol O-methyltransferase Val108/158Met polymorphism and alexithymia. Neuropsychobiol 2005; 52: 151-154
• 110 Walter NT, Montag C, Markett SA, Reuter M. Interaction effect of functional variants of the BDNF and DRD2/ANKK1 gene is associated with alexithymia in healthy human subjects. Psychosom Med 2011; 73: 23-28
• 111 Koh MJ, Kang JI, Namkoong K, Lee SY, Kim SJ. Association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder. Yonsei Med J 2016; 57: 721-727
• 112 Ernst J, Böker H, Hättenschwiler J, Schüpbach D, Northoff G, Seifritz E. et al. The association of interoceptive awareness and alexithymia with neurotransmitter concentrations in insula and anterior cingulate. Soc Cogn Affect Neurosci 2014; 9: 857-863
• 113 Marques AH, Silverman MN, Sternberg EM. Glucocorticoid dysregulations and their clinical correlates: From receptors to therapeutics. Ann N Y Acad Sci 2009; 1179: 1-18
• 114 Kern S, Rohleder N, Eisenhofer G, Lange J, Ziemssen T. Time matters – Acute stress response and glucocorticoid sensitivity in early multiple sclerosis. Brain Behav Immun 2014; 41: 82-89
• 115 Žarković M, Ignjatović S, Dajak M, Ćirić J, Beleslin B, Savić S. et al. Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans. Eur J Endocrinol 2008; 159: 649-652
• 116 Sharp BM, Matta SG, Peterson PK, Newton R, Chao C, McAllen K. Tumor necrosis factor-α is a potent ACTH secretagogue: Comparison to interleukin-1 beta. Endocrinology 1989; 124: 3131-3133
• 117 Gwosdow AR, Kumar MSA, Bode HH. Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis. Am J Physiol – Endocrinol Metab 1990; 258: e65-e70
• 118 Michelson D, Stone L, Galliven E, Magiakou MA, Chrousos GP, Sternberg EM. et al. Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function. J Clin Endocrinol Metab 1994; 79: 848-853
• 119 Fassbender K, Schmidt R, Mößner R, Kischka U, Kühnen J, Schwarte A. et al. Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: Association with cerebral inflammation. Arch Neurol 1998; 55: 66-72
• 120 Bergh FT, Kümpfel T, Trenkwalder C, Rupprecht R, Holsboer F. Dysregulation of the hypothalamopituitary-adrenal axis is related to the clinical course of MS. Neurology 1999; 53: 772-777
• 121 Huitinga I, Erkut ZA, Van Beurden D, Swaab DF. Impaired Hypothalamus-Pituitary-Adrenal Axis Activity and More Severe Multiple Sclerosis with Hypothalamic Lesions. Ann Neurol 2004; 55: 37-45
• 122 Gold SM, Raji A, Huitinga I, Wiedemann K, Schulz KH, Heesen C. Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis. J Neuroimmunol 2005; 165: 186-191
• 123 Ysrraelit MC, Gaitán MI, Lopez AS, Correale J. Impaired hypothalamic-pituitary-adrenal axis activity in patients with multiple sclerosis. Neurology 2008; 71: 1948-1954
• 124 Melief J, De Wit SJ, Van Eden CG, Teunissen C, Hamann J, Uitdehaag BM. et al. HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter. Acta Neuropathol 2013; 126: 237-249
• 125 McCaslin SE, Rogers CE, Metzler TJ, Best SR, Weiss DS, Fagan JA. et al. The impact of personal threat on police officers’ responses to critical incident stressors. J Nerv Ment Dis 2006; 194: 591-597
• 126 Gil FP, Bidlingmaier M, Ridout N, Scheidt CE, Caton S, Schoechlin C. et al. The relationship between alexithymia and salivary cortisol levels in somatoform disorders. Nord J Psychiatry 2008; 62: 366-373
• 127 Alkan Härtwig E, Aust S, Heuser I. HPA system activity in alexithymia: A cortisol awakening response study. Psychoneuroendocrinol 2013; 38: 2121-2126
• 128 de Timary P, Roy E, Luminet O, Fillée C, Mikolajczak M. Relationship between alexithymia, alexithymia factors and salivary cortisol in men exposed to a social stress test. Psychoneuroendocrinol 2008; 33: 1160-1164
• 129 Hua J, Le Scanff C, Larue J, José F, Martin JC, Devillers L. et al. Global stress response during a social stress test: Impact of alexithymia and its subfactors. Psychoneuroendocrinol 2014; 50: 53-61
• 130 Martin JB. The stress-alexithymia hypothesis: Theoretical and empirical considerations. Psychother Psychosom 1985; 43: 169-176
• 131 Friedlander L, Lumley MA, Farchione T, Doyal G. Testing the alexithymia hypothesis: Physiological and subjective responses during relaxation and stress. J Nerv Ment Dis 1997; 185: 133-139
• 132 Fries E, Hesse J, Hellhammer J, Hellhammer DH. A new view on hypocortisolism. Psychoneuroendocrinology 2005; 30: 1010-1016
• 133 Papciak AS, Feuerstein M, Spiegel JA. Stress reactivity in alexithymia: Decoupling of physiological and cognitive responses. J Human Stress 1985; 11: 135-142
• 134 Martin JB, Pihl RO. Influence of alexithymic characteristics on physiological and subjective stress responses in normal individuals. Psychother Psychosom 1986; 45: 66-77
• 135 Rabavilas AD. Electrodermal activity in low and high alexithymia neurotic patients. Psychother Psychosom 1987; 47: 101-104
• 136 Infrasca R. Alexithymia, neurovegetative arousal and neuroticism. An experimental study. Psychother Psychosom 1997; 66: 276-280
• 137 Fukunishi I, Sei H, Morita Y, Rahe RH. Sympathetic activity in alexithymics with mother’s low care. J Psychosom Res 1999; 46: 579-589
• 138 Stone LA, Nielson KA. Intact physiological response to arousal with impaired emotional recognition in alexithymia. Psychother Psychosom 2001; 70: 92-102
• 139 Gündel H, Von Rad M, Greiner A, Förstl H, Jahn T, Ceballos-Baumann AO. Increased level of tonic sympathetic arousal in high- vs. low-alexithymic cervical dystonia patients. Psychother Psychosom Med Psychol 2002; 52: 461-468
• 140 Wehmer F, Brejnak C, Lumley M, Stettner L. Alexithymia and physiological reactivity to emotion-provoking visual scenes. J Nerv Ment Dis 1995; 183: 351-357
• 141 Linden W, Lenz JW, Stossel C. Alexithymia, defensiveness and cardiovascular reactivity to stress. J Psychosom Res 1996; 41: 575-583
• 142 Barbas H, Saha S, Rempel-Clower N, Ghashghaei T. Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression. BMC Neurosci 2003; 4: 25
• 143 Simpson JR, Snyder AZ, Gusnard DA, Raichle ME. Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance. Proc Natl Acad Sci U S A 2001; 98: 683-687
• 144 Gianotti G. Disorders of emotional behaviour. J Neurol 2001; 248: 743-749
• 145 Pavlou M, Stefoski D. Development of somatizing responses in multiple sclerosis. Psychother Psychosom 1983; 39: 236-243
• 146 Grant I. Neuropsychological and psychiatric disturbances in multiple sclerosis. In: McDonald WI, Silberberg DH (eds). Multiple Sclerosis. London: Butterworths; 1986
• 147 Rubens AB, Froehling B, Slater G, Anderson D. Left ear suppression on verbal dichotic tests in patients with multiple sclerosis. Ann Neurol 1985; 18: 459-463
• 148 Lindeboom J, ter Horst R. Interhemispheric disconnection effects in multiple sclerosis. J Neurol Neurosurg Psychiatry 1988; 51: 1445-1447
• 149 Rao SM, Bernardin L, Leo GJ, Ellington L. Cerebral Disconnection in Multiple Sclerosis: Relationship to Atrophy of the Corpus Callosum. Arch Neurol 1989; 46: 918-920
• 150 Pelletier J, Habib M, Poncet M, Khalil R, Salamon G, Lyon Caen O. Functional and Magnetic Resonance Imaging Correlates of Callosal Involvement in Multiple Sclerosis. Arch Neurol 1993; 50: 1077-1082
• 151 Montreuil M, Jouvent R. The phenomenon of visual parallel detection. Construction and validation of a test and application to a psychosomatic model. Encephale 1989; 15: 409-413
• 152 Pelletier J, Suchet L, Witjas T, Habib M, Guttmann CRG, Salamon G. et al. A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis. Arch Neurol 2001; 58: 105-111
• 153 Wishart HA, Strauss E, Hunter M, Moll A. Interhemispheric Transfer in Multiple Sclerosis. J Clin Exp Neuropsychol 1995; 17: 937-940
• 154 Brown LN, Metz LM, Sainsbury RS. Sensory Temporal Thresholds and Interhemispheric Transfer Times in Multiple Sclerosis: A Preliminary Study of a New Outcome Measure. J Clin Exp Neuropsychol 2003; 25: 783-792
• 155 Brown LN, Zhang Y, Mitchell JR, Zabad R, Metz LM. Corpus callosum volume and interhemispheric transfer in multiple sclerosis. Can J Neurol Sci 2010; 37: 615-619
• 156 Warlop NP, Achten E, Debruyne J, Vingerhoets G. Diffusion weighted callosal integrity reflects interhemispheric communication efficiency in multiple sclerosis. Neuropsychologia 2008; 46: 2258-2264
• 157 Bonzano L, Tacchino A, Roccatagliata L, Mancardi GL, Abbruzzese G, Bove M. Structural integrity of callosal midbody influences intermanual transfer in a motor reaction-time task. Hum Brain Mapp 2011; 32: 218-228
• 158 Briones-Buixassa L, Milà R, Arrufat FX, Aragonès JM, Bufill E, Luminet O. et al. A case-control study of psychosocial factors and their relationship to impairment and functionality in multiple sclerosis. J Health Psychol 2019; 24: 1023-1032
• 159 Eboni ACB, Cardoso M, Dias FM, da Gama PD, Gomes S, Goncalves MVM. et al. High levels of alexithymia in patients with multiple sclerosis. Dement e Neuropsychol 2018; 12: 212-215
• 160 Dulau C, Deloire M, Diaz H, Saubusse A, Charre-Morin J, Prouteau A. et al. Social cognition according to cognitive impairment in different clinical phenotypes of multiple sclerosis. J Neurol 2017; 264: 740-748
• 161 Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun 2007; 21: 374-383
• 162 Gay MC, Vrignaud P, Garitte C, Meunier C. Predictors of depression in multiple sclerosis patients. Acta Neurol Scand 2010; 121: 161-170
• 163 Chahraoui K, Pinoit JM, Bonin B, Viegas N, Adnet J, Moreau T. Alexithymia and links with depression and anxiety in multiple sclerosis. Rev Neurol (Paris) 2008; 164: 242-245
• 164 Sá MJ. Psychological aspects of multiple sclerosis. Clin Neurol Neurosurg 2008; 110: 868-877
• 165 Chalah MA, Kauv P, Créange A, Hodel J, Lefaucheur JP, Ayache SS. Neurophysiological, radiological and neuropsychological evaluation of fatigue in multiple sclerosis. Mult Scler Relat Disord 2019; 28: 145-152
• 166 Cecchetto C, Aiello M, D’Amico D, Cutuli D, Cargnelutti D, Eleopra R. et al. Facial and bodily emotion recognition in multiple sclerosis: The role of alexithymia and other characteristics of the disease. J Int Neuropsychol Soc 2014; 20: 1004-1014
• 167 Bodini B, Mandarelli G, Tomassini V, Tarsitani L, Pestalozza I, Gasperini C. et al. Alexithymia in multiple sclerosis: Relationship with fatigue and depression. Acta Neurol Scand 2008; 118: 18-23
• 168 Phillips LH, Saldias A, McCarrey A, Henry JD, Scott C, Summers F. et al. Attentional lapses, emotional regulation and quality of life in multiple sclerosis. Br J Clin Psychol 2009; 48: 101-106
• 169 Phillips LH, Henry JD, Nouzova E, Cooper C, Radlak B, Summers F. Difficulties with emotion regulation in multiple sclerosis: Links to executive function, mood, and quality of life. J Clin Exp Neuropsychol 2014; 36: 831-842
• 170 Gay MC, Bungener C, Thomas S, Vrignaud P, Thomas PW, Baker R. et al. Anxiety, emotional processing and depression in people with multiple sclerosis. BMC Neurol 2017; 17: 43
• 171 Mosson M, Peter L, Montel S. Impact of physical activity level on alexithymia and coping strategies in an over-40 multiple sclerosis population: A pilot study. Rev Neurol (Paris) 2014; 170: 19-25
• 172 Parker PD, Prkachin KM, Prkachin GC. Processing of facial expressions of negative emotion in alexithymia: The influence of temporal constraint. J Pers 2005; 73: 1087-1107
• 173 Goldman AI, Sripada CS. Simulationist models of face-based emotion recognition. Cognition 2005; 94: 193-213
• 174 Prkachin GC, Casey C, Prkachin KM. Alexithymia and perception of facial expressions of emotion. Pers Individ Dif 2009; 46: 412-417
• 175 McDonald PW, Prkachin KM. The expression and perception of facial emotion in alexithymia: A pilot study. Psychosom Med 1990; 52: 199-210
• 176 Moriguchi Y, Ohnishi T, Lane RD, Maeda M, Mori T, Nemoto K. et al. Impaired self-awareness and theory of mind: An fMRI study of mentalizing in alexithymia. Neuroimage 2006; 32: 1472-1482
• 177 Moriguchi Y, Decety J, Ohnishi T, Maeda M, Mori T, Nemoto K. et al. Empathy and judging other’s pain: An fMRI study of alexithymia. Cereb Cortex 2007; 17: 2223-2234
• 178 Guttman H, Laporte L. Alexithymia, empathy, and psychological symptoms in a family context. Compr Psychiatry 2002; 43: 448-455
• 179 Feldman Hall O, Dalgleish T, Mobbs D. Alexithymia decreases altruism in real social decisions. Cortex 2013; 49: 899-904
• 180 Prochnow D, Höing B, Kleiser R, Lindenberg R, Wittsack HJ, Schäfer R. et al. The neural correlates of affect reading: An fMRI study on faces and gestures. Behav Brain Res 2013; 237: 270-277
• 181 Bogdanov VB, Bogdanova OV., Gorlov DS, Gorgo YP, Dirckx JJ, Makarchuk MY. et al. Alexithymia and empathy predict changes in autonomic arousal during affective stimulation. Cogn Behav Neurol 2013; 26: 121-132
• 182 Neumann D, Zupan B, Malec JF, Hammond F. Relationships between alexithymia, affect recognition, and empathy after traumatic brain injury. J Head Trauma Rehabil 2014; 29: 318-327
• 183 Aaron RV, Benson TL, Park S. Investigating the role of alexithymia on the empathic deficits found in schizotypy and autism spectrum traits. Pers Individ Dif 2015; 77: 215-220
• 184 Barsalou L. Grounded cognition. Annu Rev Psychol 2008; 59: 617-645
• 185 Lamm C, Bukowski H, Silani G. From shared to distinct self-other representations in empathy: Evidence from neurotypical function and socio-cognitive disorders. Philos Trans R Soc B Biol Sci 2016; 371: 20150083
• 186 Ochsner KN, Knierim K, Ludlow DH, Hanelin J, Ramachandran T, Glover G. et al. Reflecting upon feelings: An fMRI study of neural systems supporting the attribution of emotion to self and other. J Cogn Neurosci 2004; 16: 1746-1772
• 187 Bird G, Silani G, Brindley R, White S, Frith U, Singer T. Empathic brain responses in insula are modulated by levels of alexithymia but not autism. Brain 2010; 133: 1515-1525
• 188 Al Aïn S, Carré A, Fantini-Hauwel C, Baudouin JY, Besche-Richard C. What is the emotional core of the multidimensional machiavellian personality trait?. Front Psychol 2013; 4: 454
• 189 Lockwood PL, Bird G, Bridge M, Viding E. Dissecting empathy: High levels of psychopathic and autistic traits are characterized by difficulties in different social information processing domains. Front Hum Neurosci 2013; 7: 760
• 190 Gleichgerrcht E, Tomashitis B, Sinay V. The relationship between alexithymia, empathy and moral judgment in patients with multiple sclerosis. Eur J Neurol 2015; 22: 1295-1303
• 191 Patil I, Young L, Sinay V, Gleichgerrcht E. Elevated moral condemnation of third-party violations in multiple sclerosis patients. Soc Neurosci 2017; 12: 308-329