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Psycho-neuro-endocrino-immunologic issues in multiple sclerosis: a critical review of clinical and therapeutic implications

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Abstract

Multiple sclerosis (MS) is a multifactorial, chronic, immune-mediated, and neurodegenerative disease, having a well-known hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Several hormones have a great impact in the immune dysregulation, psychology, and cognitive status of patients with MS, as also in the fertility and response to treatment. In this comprehensive review, as an introduction, we mention basic data concerning MS: epidemiology, genetics, immunogenetics, epigenetics, pathophysiology, and neuroimmunology. Hormonal components of the disease cascade, mainly glucocorticoids (stress-related hormone), estrogens, prolactin and dehydroepiandrosterone (sex-related hormones), melatonin, and vitamin D, are discussed, aiming at focusing on core data regarding the impact of these hormones in MS pathophysiology, severity of the disease, correlation with comorbid mental disorders, and fertility. A great focus is given in the pre- and post-pregnancy period of MS patients, in the context of the disease-modifying treatments (DMTs) and HPA status, having in mind that there are only very limited knowledge and few papers on this specific life period of these women, having MS. All this data are presented in the main text and also in the workable tables, for the first time, suggesting targeted topics that need to be addressed in the near future.

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Abbreviations

MS:

Multiple sclerosis

RRMS:

Relapsing remitting multiple sclerosis

PPMS:

Primary progressive multiple sclerosis

SPMS:

Secondary progressive multiple sclerosis

CNS:

Central nervous system

GWAS:

Genome-wide association studies

HLA:

Human leucocyte antigen

DMTs:

Disease-modifying treatments

HPA:

Hypothalamic-pituitary-adrenal

PSS:

Psychosocial stress

DHEA:

Dehydroepiandrosterone

TNF:

Tumor necrosis factor

SAM:

Sympathetic-adrenomedullary system

GC:

Glucocorticoid/s

CRH:

Corticotropin-releasing hormone

ACTH:

Adrenocorticotropic hormone

GRs:

Glucocorticoid receptors

MRs:

Mineralocorticoid receptors

DCs:

Dendritic cells

MHC:

Major histocompatibility complex

EAE:

Experimental autoimmune encephalomyelitis

GnRH:

Gonadotropin-releasing hormone

ER:

Estrogen receptor

PRL:

Prolactin

BD:

Bipolar disorder

SCZ:

Schizophrenia

GA:

Glatiramer acetate

NF-κΒ:

Nuclear factor kappa-light-chain-enhancer of activated B cells

STATs:

Signal transducer and activator of transcription

ICAM-1:

Intercellular adhesion molecule

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Authors and Affiliations

  1. Demyelinating Diseases Clinic, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition Hospital, Vasilissis Sofias 72-74, 115 28, Athens, Greece

    Maria Anagnostouli

  2. Immunogenetics Laboratory, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition Hospital, Vasilissis Sofias 72-74, 115 28, Athens, Greece

    Maria Anagnostouli & Nikolaos Markoglou

  3. University Research Institute of Maternal and Child Health and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    George Chrousos

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  1. Maria Anagnostouli
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Anagnostouli, M., Markoglou, N. & Chrousos, G. Psycho-neuro-endocrino-immunologic issues in multiple sclerosis: a critical review of clinical and therapeutic implications. Hormones 19, 485–496 (2020). https://doi.org/10.1007/s42000-020-00197-8

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