Dataset Information

Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort.

ABSTRACT:

Background

Consistent findings on underlying brain features or specific structural atrophy patterns contributing to depression in multiple sclerosis (MS) are limited.

Objective

To investigate how deep gray matter (DGM) features predict depressive symptom trajectories in MS patients.

Methods

We used data from the MS Partners Advancing Technology and Health Solutions (MS PATHS) network in which standardized patient information and outcomes are collected. We performed whole-brain segmentation using SLANT-CRUISE. We assessed if DGM structures were associated with elevated depressive symptoms over follow-up and with depressive symptom phenotypes.

Results

We included 3844 participants (average age: 46.05 ± 11.83 years; 72.7% female) of whom 1905 (49.5%) experienced ⩾1 periods of elevated depressive symptoms over 2.6 ± 0.9 years mean follow-up. Higher caudate, putamen, accumbens, ventral diencephalon, thalamus, and amygdala volumes were associated with lower odds of elevated depressive symptoms over follow-up (odds ratio (OR) range per 1 SD (standard deviation) increase in volume: 0.88-0.94). For example, a 1 SD increase in accumbens or caudate volume was associated with 12% or 10% respective lower odds of having a period of elevated depressive symptoms over follow-up (for accumbens: OR: 0.88; 95% confidence interval (CI): 0.83-0.93; p < 0.001; for caudate: OR: 0.90; 95% CI: 0.85-0.96; p = 0.003).

Conclusion

Lower DGM volumes were associated with depressive symptom trajectories in MS.

SUBMITTER: Hu C

PROVIDER: S-EPMC10277218 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort.

Hu Chen C Dewey Blake E BE Mowry Ellen M EM Fitzgerald Kathryn C KC

Multiple sclerosis (Houndmills, Basingstoke, England) 20230124 7

<h4>Background</h4>Consistent findings on underlying brain features or specific structural atrophy patterns contributing to depression in multiple sclerosis (MS) are limited.<h4>Objective</h4>To investigate how deep gray matter (DGM) features predict depressive symptom trajectories in MS patients.<h4>Methods</h4>We used data from the MS Partners Advancing Technology and Health Solutions (MS PATHS) network in which standardized patient information and outcomes are collected. We performed whole-br ...[more]

PMID: 36691798

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Project description:ObjectiveThis study aimed to investigate longitudinal deep gray matter (DGM) shape changes and their relationship with measures of clinical disability and white matter lesion-load in a large multiple sclerosis (MS) cohort.Materials and methodsA total of 230 MS patients (179 relapsing-remitting, 51 secondary progressive; baseline age 44.5 ± 11.3 years; baseline disease duration 12.99 ± 9.18) underwent annual clinical and MRI examinations over a maximum of 6 years (mean 4.32 ± 2.07 years). The DGM structures were segmented on the T1-weighted images using the "Multiple Automatically Generated Templates" brain algorithm. White matter lesion-load was measured on T2-weighted MRI. Clinical examination included the expanded disability status scale, 9-hole peg test, timed 25-foot walk test, symbol digit modalities test and paced auditory serial addition test. Vertex-wise longitudinal analysis of DGM shapes was performed using linear mixed effect models and evaluated the association between average/temporal changes of DGM shapes with average/temporal changes of clinical measurements, respectively.ResultsA significant shrinkage over time of the bilateral ventrolateral pallidal and the left posterolateral striatal surface was observed, whereas no significant shape changes over time were observed at the bilateral thalamic and right striatal surfaces. Higher average lesion-load was associated with an average inwards displacement of the global thalamic surface with relative sparing on the posterior side (slight left-side predominance), the antero-dorso-lateral striatal surfaces bilaterally (symmetric on both sides) and the antero-lateral pallidal surface (left-side predominance). There was also an association between shrinkage of large lateral DGM surfaces with higher clinical motor and cognitive disease severity. However, there was no correlation between any DGM shape changes over time and measurements of clinical progression or lesion-load changes over time.ConclusionsThis study showed specific shape change of DGM structures occurring over time in relapse-onset MS. Although these shape changes over time were not associated with disease progression, we demonstrated a link between DGM shape and the patients' average disease severity as well as white matter lesion-load.

Project description:Background and purposeDeep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures.Materials and methodsForty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.ResultsCompared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.ConclusionsQuantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

Project description:OBJECTIVE:Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. METHODS:We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. RESULTS:SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION:This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222.

Project description:Background and purposeModifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS.Materials and methodsQuantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models.ResultsWe identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = -0.341, P = .02), iron concentration (B = -0.379, P = .005) and content (B = -0.406, P = .009), as well as pulvinar iron (B = -0.415, P = .003) and myelin (B = -0.415, P = .02) content, independent of atrophy.ConclusionsQuantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.

Dataset Information

Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort.

Background

Objective

Methods

Results

Conclusion

Publications

Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort.

Similar Datasets

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