Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception

Santoro, Massimo; Nociti, Viviana; Fino, Chiara De; Caprara, Ana Letícia Fornari; Giordano, Rocco; Palomba, Nicole Piera; Losavio, Francesco Antonio; Marra, Camillo; Patanella, Agata Katia; Mirabella, Massimiliano; Gainotti, Guido; Quaranta, Davide

doi:10.1111/ene.12913

Cited by 14 publications

(10 citation statements)

References 71 publications

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“…In a Polish cohort, the Val homozygotes were found to have increased MS susceptibility in females and earlier onset of disease in males, suggesting a gender difference in the effect of the polymorphism on MS [ 38 ]. The BDNF Val66Met polymorphism showed no significant influence on the severity of depression in MS patients, though the result was in disagreement with the findings based in the general population [ 85 ]. Negative results were also reported in MS susceptibility and clinical course in human cohorts from the UK, Norway, and Spain [ 44 , 86 , 87 ].…”

Section: The Effects Of Val66met Polymorphism On Neurodegenerative DIcontrasting

confidence: 76%

BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders

et al. 2018

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Brain-derived neurotrophic factor (BDNF) has a unique role in the neuronal development, differentiation, and survival in the developing and adult nervous system. A common single-nucleotide polymorphism in the pro-region of the human BDNF gene, resulting in a valine to methionine substitution (Val66Met), has been associated with the susceptibility, incidence, and clinical features of several neurodegenerative disorders. Much research has been dedicated to evaluating the effects of polymorphism in the past decade, and functional effects of this genetic variation. A better understanding of how this naturally occurring polymorphism associates with or influences physiology, anatomy, and cognition in both healthy and diseased adults in neurodegenerative conditions will help understand neurochemical mechanisms and definable clinical outcomes in humans. Here we review the role and relevance of the BDNF Val66Met polymorphism in neurodegenerative diseases, with particular emphasis on glaucoma, multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several controversies and unresolved issues, including small effect sizes, possible ethnicity, gender, and age effects of the BDNF Val66Met are also discussed with respect to future research.

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Section: The Effects Of Val66met Polymorphism On Neurodegenerative DIcontrasting

confidence: 76%

BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders

et al. 2018

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“…Methylation analysis was focused upon genomic region including one CpG site that can be created or abolished by rs6265 SNP ( Fig 1A ). Before methylation analysis, we performed genotyping for this polymorphism in our cohort of study using HRM technique [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…We analyzed the BDNF rs6265 polymorphism using HRM technique that characterizes nucleic acid samples based on their disassociation (melting) behavior using StepOnePlus thermocycler (Applied Biosystems, Foster City, CA, USA). The amplification of BDNF rs6265 polymorphism was carried out as previously reported [ 27 ]: in brief, the reaction mix (total volume of 20μl), contained 20 nanograms (ng) of genomic DNA, 0.5 μM of either forward/reverse primers and 1X of MeltDoctor HRM Master Mix (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

et al. 2018

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IntroductionBrain-Derived Neurotrophic Factor (BDNF) and its most common polymorphism Val66Met are known to have a role in Multiple Sclerosis (MS) pathogenesis. Evidence is accumulating that there is an involvement of DNA methylation in the regulation of BDNF expression. The aim of this study was to assess in blood samples of MS patients the correlation between the methylation status of the CpG site near BDNF-Val66Met polymorphism and the severity of the disease.MethodsWe recruited 209 MS patients that were genotyped for the BDNF Val66Met polymorphism. For each patient we quantitatively measured the methylation level of cytosine included in the exonic CpG site that can be created or abolished by the Val66Met BDNF polymorphism. Furthermore, we analyzed the clinical history of each patient and determined the time elapsed since the onset of the disease and an EDSS score of 6.0.ResultsThe genetic analysis identified 122 (58.4%) subjects carrying the Val/Val genotype, 81 (38.8%) with Val/Met genotype, and 6 (2.8%) carrying the Met/Met genotype. When the endpoint of an EDSS score of 6 was taken into account by means of a survival analysis, 52 failures (i.e., reaching an EDSS score of 6) were reported. When the sample was stratified according to the percentage of the BDNF methylation, subjects falling below the median (median methylation = 81%) were at higher risk of failure (IRD = 0.016; 95%CI = 0.0050–0.0279; p = 0.004).ConclusionsIn patients with a high disease progression the hypomethylation of the BDNF gene could increase the secretion of the protective neurotrophin, so epigenetic modifications could be the organism response to limit a brain functional reserve loss. Our study suggests that the percentage of methylation of the BDNF gene could be used as a prognostic factor for disease progression toward a high disability in MS patient.

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“…Communication and education were considered essential for raising awareness and understanding of MS and dispelling misconceptions about the disease. Misconceptions about MS can hinder acceptance of the diagnosis in new PwMS (Fallahi-Khoshknab et al, 2014) and can cause health anxiety in all PwMS, with a subsequent impact on QoL, perception of symptoms (Hayter et al, 2016), and an increased risk of depression (Santoro et al, 2016). Conversely, positive personal perceptions about MS, such as a perception of treatment control or a realistic MS timeline perspective, are more strongly correlated with disease self-management than are objective clinical variables such as the severity, type and duration of MS (Wilski and Tasiemski, 2016).…”

Section: Foster Greater Understanding and Awareness Of The Challengesmentioning

confidence: 99%

Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: A combined perspective from the MS in the 21st Century Steering Group

Rieckmann¹,

Centonze

Elovaara

et al. 2018

Multiple Sclerosis and Related Disorders

110

102

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Our study of PwMS and HCPs in the MS in the 21st Century initiative has highlighted eight practical actions. These actions identify how differences and gaps in unmet needs, treatment burden, and patient engagement between PwMS and HCPs can be bridged to improve MS disease management. Of particular interest now are patient-centred educational resources that can be used during time-limited consultations to enhance understanding of disease and improve communication. Actively bridging these gaps in a joint approach enables PwMS to take part in shared decision-making; with improved communication and reliable information, patients can make informed decisions with their HCPs, as part of their own personalised disease management.

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Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception

Abstract: Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

Cited by 14 publications

References 71 publications

BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders

BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders

BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: A combined perspective from the MS in the 21st Century Steering Group

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