Dataset Information

The longitudinal relationship between fatigue, depression, anxiety, disability, and adherence with cognitive status in patients with early multiple sclerosis treated with interferon beta-1a.

ABSTRACT:

Background

Cognitive dysfunction is common in multiple sclerosis and may worsen with reduced treatment adherence. We examined longitudinal relationships between anxiety, depression, fatigue, disability and adherence with cognitive status in patients with relapsing-remitting multiple sclerosis (MS) treated with interferon beta-1a in four countries.

Methods

The Confidence study is a prospective study in 165 people with MS with four visits (baseline/12/24/36 months). Physical and psychological symptoms were assessed using standardized questionnaires. Adherence was calculated as the number of injections divided by number of expected injections. Cognitive status was assessed by the Brief Repeatable Battery of Neuropsychological Tests and converted to a global Z-score.

Results

At baseline, mean age was 35.7 ± 11 years and 66% were female (n = 109). Adherence to treatment was very high throughout the study (>99%). A depression score ≥ 8 was significantly associated with a higher risk of low cognitive status compared with a lower score (0-7): relative risk 1.79 (1.14-2.83) adjusted for education and time since diagnosis. The P-value-for-time was not significant (P = 0.304) meaning that associations existed since baseline and remained stable during follow-up.

Conclusion

Our findings provide evidence for a longitudinal association between depression and low cognitive status in patients treated with interferon beta-1a in routine medical practice.

SUBMITTER: van Ballegooijen H

PROVIDER: S-EPMC9207145 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

The longitudinal relationship between fatigue, depression, anxiety, disability, and adherence with cognitive status in patients with early multiple sclerosis treated with interferon beta-1a.

van Ballegooijen Hanne H van der Hiele Karin K Enzinger Christian C de Voer Gert G Visser Leo H LH

eNeurologicalSci 20220614

<h4>Background</h4>Cognitive dysfunction is common in multiple sclerosis and may worsen with reduced treatment adherence. We examined longitudinal relationships between anxiety, depression, fatigue, disability and adherence with cognitive status in patients with relapsing-remitting multiple sclerosis (MS) treated with interferon beta-1a in four countries.<h4>Methods</h4>The Confidence study is a prospective study in 165 people with MS with four visits (baseline/12/24/36 months). Physical and psy ...[more]

PMID: 35733640

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Project description:Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy.

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Project description:Interferon-alpha (IFN-?) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-? on immune cells in vivo and its relationship to IFN-?-induced behavioral changes.Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-? therapy (n=10) or at 12 weeks of IFN-? treatment (n=11).Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2'-5'-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-?-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-?-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-? signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-?-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-? and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.Depression and fatigue during chronic IFN-? administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

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Dataset Information

The longitudinal relationship between fatigue, depression, anxiety, disability, and adherence with cognitive status in patients with early multiple sclerosis treated with interferon beta-1a.

Background

Methods

Results

Conclusion

Publications

The longitudinal relationship between fatigue, depression, anxiety, disability, and adherence with cognitive status in patients with early multiple sclerosis treated with interferon beta-1a.

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