Deciphering Depressive Mood in Relapsing-Remitting and Progressive Multiple Sclerosis and Its Consequence on Quality of Life

<div><p>Background</p><p>Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the “Echelle d’Humeur Dépressive” (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS).</p><p>Objectives</p><p>First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR-QOL).</p><p>Results</p><p>Regardless of their phenotype, PwMS had significantly higher EHD-PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD-PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL.</p><p>Conclusion</p><p>The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS.</p></div

Linear regression models describing EHD scores in PwPPMS.

<p>^a variables significantly correlated with EHD scores in multivariate analyses.</p><p>^b variables with a p value <0.25 in univariate analyses. Age, gender, EDSS score were included in multivariate analyses.</p><p>PPMS: primary progressive multiple sclerosis. EDSS: Expanded Disability Status Scale; BDI-FS: Beck Depression Inventory-Fast Screen; S-Anxiety: State Anxiety scale of State-Trait Anxiety Inventory-State Form Y; EHD-EC-PRO: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB-PRO: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes; EHD-PRO: total score corresponding to an addition of EHD-EC and EHD-EB.</p><p>Linear regression models describing EHD scores in PwPPMS.</p

Multivariate analyses of HR-QOL in RRMS patients (models including EHD PRO-subscales).

<p>^a variables significantly correlated with EHD scores in multivariate analyses.</p><p>^b variables with a p value <0.25 in univariate analyses. Age, gender, EDSS score were included in multivariate analyses.</p><p>RRMS, relapsing–remitting multiple sclerosis. HR-QOL: Health-Related Quality of life; PCS/SF-36: Physical Composite Score of the Short-Form-36 MCS/SF-36: Mental Composite Score of the Short-Form-36; EHD-EC: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes.</p><p>Multivariate analyses of HR-QOL in RRMS patients (models including EHD PRO-subscales).</p

Clinical and PRO scores of PwMS.

<p>F: female; M: male. RRMS, relapsing–remitting multiple sclerosis; PPMS, primary progressive MS. For all clinical data, scores are expressed as the mean ± standard deviation (SD), except for EDSS, which are expressed as the median (range).</p><p>EDSS: Expanded Disability Status Scale; BDI: Beck Depression Inventory II; BDI-FS: Beck Depression Inventory-Fast screen; STAI-S: State Anxiety scale of State-Trait Anxiety Inventory-State Form Y; EHD-PRO: Echelle d’Humeur Dépressive-Patient-reported outcomes; EHD-EC: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes; EHD-PRO: total score corresponding to an addition of EHD-EC and EHD-EB; PCS/SF-36 MCS/SF-36. p values from a chi-squared test comparing sex; p values from non-matched t-tests comparing means; p values between each MS group and matched controls, 60 PwRRMS and 310 matched controls, 41 PwPPMS and 263 matched controls: ^ns,non significant</p><p>*<0.05</p><p>**<0.01</p><p>***<0.001.</p><p>Clinical and PRO scores of PwMS.</p

Multivariate analyses of HR-QOL in PPMS patients (models including EHD PRO-subscales).

<p>^a variables significantly correlated with EHD scores in multivariate analyses.</p><p>^b variables with a p value <0.25 in univariate analyses. Age, gender, EDSS score were included in multivariate analyses</p><p>^ns: non significant</p><p>PPMS, primary progressive multiple sclerosis. HR-QOL: Health-Related Quality of life; PCS/SF-36: Physical Composite Score of the Short-Form-36 MCS/SF-36: Mental Composite Score of the Short-Form-36; EHD-EC: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes.</p><p>Multivariate analyses of HR-QOL in PPMS patients (models including EHD PRO-subscales).</p

Linear regression model describing EHD scores in PwRRMS.

<p>^a variables significantly correlated with EHD scores in multivariate analyses.</p><p>^b variables with a p value <0.25 in univariate analyses. Age, gender, EDSS score were included in multivariate analyses.</p><p>RRMS: relapsing–remitting multiple sclerosis; EDSS: Expanded Disability Status Scale; BDI-FS: Beck Depression Inventory-Fast Screen; S-Anxiety: State Anxiety scale of State-Trait Anxiety Inventory-State Form Y; EHD-EC: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes; EHD-PRO: total score corresponding to an addition of EHD-EC and EHD-EB.</p><p>Linear regression model describing EHD scores in PwRRMS.</p

Multivariate analysis model 2 –Cognitive prediction and MD analysis.

<p>Multivariate analysis model 2 –Cognitive prediction and MD analysis.</p

Microstructural analyses of the posterior cerebellar lobules in relapsing-onset multiple sclerosis and their implication in cognitive impairment - Fig 1

<p>A: Detailed image processing used to obtain lobular and peduncular diffusity data. Cropping and non-linear registration of T1w images over the SUIT template and ROI delineation. B: Registration of the diffusivity map using the transformation estimated with the T1w, diffusivity estimation into ROI. C: Non-linear registration of diffusivity maps and estimation within ROI determined by the JHU-ICBM-DTI-81 WM atlas (FSL).</p

Multivariate analysis model 1 –Cognitive prediction and FA analysis.

<p>Multivariate analysis model 1 –Cognitive prediction and FA analysis.</p

Correlations between MD and cognitive outcome.

<p>Correlations between MD and cognitive outcome.</p