Depression and anxiety disorders in patients with multiple sclerosis: association with neurodegeneration and neurofilaments

Tauil, Carlos Bernardo; Rocha-Lima, A D; Ferrari, Breno B; Silva, F M da; Machado, Luı́s dos Ramos; Ramari, Cintia; Brandão, Carlos Otávio; Santos, Leonilda Maria Barbosa dos; Santos-Neto, Leopoldo Luiz dos

doi:10.1590/1414-431x202010428

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…These results expand those of prior papers demonstrating that serum levels of NF-L are higher in MDD and treatment-resistant depression (Chen et al, 2022; Domingues et al, 2019; Jakobsson et al, 2014; Rathbone et al, 2018; Spanier et al, 2019). Other research indicates that the mean CSF and serum concentration of NF-L is higher in individuals with bipolar disorder and other mental illnesses compared to healthy controls (Isgren et al, 2017; Spanier et al, 2019; Tauil et al, 2021). People with MDD have lower cognitive function when their serum NF-L levels are higher (Bavato et al, 2021) and people with post-stroke depression also have higher serum NF-L levels (Zhao et al, 2020).…”

Section: Discussionmentioning

confidence: 95%

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

Al‐Hakeim

Al-Naqeeb

Almulla

et al. 2022

Preprint

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Background. Major depressive disorder (MDD) is characterized by elevated activity of peripheral neuro-immune and neuro-oxidative pathways, which may cause neuro-affective toxicity by disrupting neuronal circuits in the brain. No study has explored peripheral indicators of neuroaxis damage in MDD in relation to serum inflammatory and insulin resistance (IR) biomarkers, calcium, and the physio-affective phenome consisting of depressive, anxious, chronic fatigue, and physiosomatic symptoms. Methods. Serum levels of phosphorylated tau protein 217 (P-tau217), platelet-derived growth factor receptor beta (PDGFR), neurofilament light chain (NF-L), glial fibrillary acidic protein (GFAP), C-reactive protein (CRP), calcium and the HOMA2-insulin resistance (IR) index were measured in 94 MDD patients and 47 controls. Results. 61.1% of the variance in the physio-affective phenome (conceptualized as a factor extracted from depression, anxiety, fatigue and physiosomatic symptoms) is explained by the regression on GFAP, NF-L, P-tau2017, PDGFRβ and HOMA2-IR (all positively associated), and decreased calcium. In addition, CRP and HOMA2-IR predicted 28.9% of the variance in the neuroaxis index. We observed significant indirect effects of CRP and calcium on the physio-affective phenome which were partly mediated by the four neuroaxis biomarkers. Annotation and enrichment analysis revealed that the enlarged GFAP, P-tau217, PDGFR, and NF-L network was enriched in glial cell and neuronal projections, the cytoskeleton and axonal transport, including a mitochondrion. Conclusions: Peripheral inflammation and IR may damage the astroglial and neuronal projections thereby interfering with mitochondrial transport. This toxicity, combined with inflammation, IR and lowered calcium, may, at least in part, induce the phenome of MDD.

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Section: Discussionmentioning

confidence: 95%

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

Al‐Hakeim

Al-Naqeeb

Almulla

et al. 2022

Preprint

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“…Yet, another study assessing 38 newly diagnosed CIS and RRMS patients reported no association between serum NfL levels and fatigue 335 . Similarly, another study found no correlation between CSF NfL levels and anxiety or depression 336 . In contrast, a significant correlation was made between baseline serum NfL levels and baseline quality of life measured by the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire, moreover serum NfL levels at baseline and follow-up correlated with changes in MSQoL-54's physical role limitations and social functioning composite scores 294 .…”

Section: Cognitive Impairmentmentioning

confidence: 92%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

Biernacki¹,

Kokas²,

Sandi³

et al. 2022

Preprint

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Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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“…Yet another study assessing 38 newly diagnosed CIS and RRMS patients reported no association between serum NfL levels and fatigue [ 330 ]. Similarly, another study found no correlation between CSF NfL levels and anxiety or depression [ 331 ]. In contrast, a significant correlation was made between baseline serum NfL levels and baseline quality of life measured by the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire; moreover, serum NfL levels at baseline and follow-up correlated with changes in MSQoL-54’s physical role limitations and social functioning composite scores [ 289 ].…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Biernacki

Kokas

Sandi

et al. 2022

IJMS

View full text Add to dashboard Cite

Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient’s health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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Depression and anxiety disorders in patients with multiple sclerosis: association with neurodegeneration and neurofilaments

Cited by 14 publications

References 37 publications

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

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