Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue

Kantorová, Ema; Poláček, Hubert; Bittšanský, Michal; Baranovičová, Eva; Hnilicová, Petra; Čierný, Daniel; Sivák, Štefan; Nosáľ, Vladimír; Zeleňák, Kamil; Kurča, Egon

doi:10.1080/01616412.2016.1275460

Cited by 46 publications

(47 citation statements)

References 34 publications

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“…The increase of Glx/NAA in our RRMS was not statistically significant at the 5% level. This, compared to our previous study with RRMS and secondary progressive (SP) patients 27 can point to lower degree of neuroaxonal loss (indicated by lower NAA) and/or generally lower burden of the disease in RRMS compared to SP stage (indicated by higher Glu).…”

Section: Differences Between Rrms Patients and Healthy Controlscontrasting

confidence: 63%

“…In addition to traditional NAA/Cr, Cho/Cr and NAA/Cho (ref. 8,9 ) we also analysed Glx/Cr, Glx/NAA and mIns/NAA ratios, being encouraged by our previous experience 27 and similar studies 10,11,17 . Since the values from both hypothalamic voxels were highly intercorrelated for all ratios in both patients and controls (r>0.5, P<0.0001), the whole hypothalamus values, calculated as the means from left and right side spectra, were used for statistical analyses.…”

Section: Evaluation Of Structural Mri and 1 H-mrs Spectramentioning

confidence: 99%

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Increased glutamate and deep brain atrophy can predict the severity of multiple sclerosis

Poláček¹,

Kantorová²,

Hnilicová³

et al. 2019

BIOMED PAP

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The results suggest that both NAA and Glx are associated with neurodegeneration of hypothalamic DGM and severe disease course. Glx related H-MRS parameters seem to be superior to other metabolites in determining disease burden, independently of otherwise powerful 3VW planimetry. Significantly increased mIns/NAA in MS patients compared to controls point to gliosis, which parallels the atrophy of hypothalamic DGM.

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Section: Differences Between Rrms Patients and Healthy Controlscontrasting

confidence: 63%

Section: Evaluation Of Structural Mri and 1 H-mrs Spectramentioning

confidence: 99%

Increased glutamate and deep brain atrophy can predict the severity of multiple sclerosis

Poláček¹,

Kantorová²,

Hnilicová³

et al. 2019

BIOMED PAP

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“…To the best of our knowledge, this study is the rst to examine the concentration of hypothalamic glutamine metabolites (Glx, Gln and Glu) in depression with no medical comorbid condition. A study by Kantorová et al studied Glx levels in patients with multiple sclerosis (MS) and healthy subjects 31 , pointing out that Glx levels in MS patients correlated positively with indicators of depression. These results are similar to the results of the current study, which show that patients with primary depression showed higher concentrations of hypothalamic glutamate metabolites than the healthy controls.…”

Section: Association Between the Peripheral Pro-in Ammatory Cytokinesmentioning

confidence: 99%

“…Despite a signi cant number of studies on MRS in depression, there are few studies that involve the hypothalamus or the HPA axis. Only one study found differences between Glx levels in depression 31 . However, this study included multiple sclerosis patients with depression, but not primarily depressed participants without comorbid illness.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: The secret behind peripheral inflammation and depression: The hypothalamus

Pedraz-Petrozzi

Blecker

Neumann

et al. 2020

Preprint

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In recent years there has been increasing evidence of an inflammatory component due to overstimulation of the hypothalamic-pituitary-adrenals (HPA) in depression. The glutamate metabolites (glutamate and glutamine) are important metabolites that are involved in this stimulation. The aim of this study was to determine the concentrations of hypothalamic glutamate metabolites in depression and to investigate their relationship to peripheral inflammation. Participants with diagnosed depression (DE; n = 24) and control subjects without depression (HC; n = 25) were investigated. Hypothalamic glutamate metabolites were recorded using in vivo magnetic resonance spectroscopy. Peripheral cytokines (IL-6, TNF-α, IFN-γ and IL-1β) were assessed using Enzyme-Linked Immunosorbent Assay. For statistical analysis, generalized mixed models were computed using Poisson distributions and a log link function. The results show overall higher hypothalamic glutamate metabolites in DE compared to HC. High TNF-a and IL-1ß concentrations are associated with high hypothalamic glutamate metabolites in DE. These results provide initial evidence that, in depression, increased HPA axis activity is associated with peripheral inflammation favored by hypothalamic glutamate metabolites.

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“…Additionally, the NAA/Glx ratio was calculated. This was based on prior literature suggesting that the ratio of NAA to glutamatergic concentrations (or vice versa) allows measurement of altered glutamatergic metabolism while correcting for the effect of neuronal loss (as indexed by NAA alone) 55,56 and may correspond to impairment in the metabolic cycling of glutamate-glutamine-NAA in neuropsychiatric disease states 57,58 .…”

Section: Group Eligibility and Classificationmentioning

confidence: 99%

Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation

et al. 2020

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The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (1 H-MRS) at 3 T, utilizing a 2-dimensional J-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluidcorrected ACC metabolite concentrations were compared between healthy control (HC, n = 16), depressed without SI (Dep/SI−, n = 13), and depressed with SI (Dep/SI+, n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and the N-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI− and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI− participants (p adj = 0.012) and had lower NAA/Glx than both Dep/SI− (p adj = 0.002) and HC adolescents (p adj = 0.039). There were significant relationships between SI intensity and Glx (p FDR = 0.026), SI severity and NAA/Glx (p FDR = 0.012), and SI intensity and NAA/Glx (p FDR = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI− from Dep/SI+ participants. Uncoupled NAA−glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.

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Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue

Cited by 46 publications

References 34 publications

Increased glutamate and deep brain atrophy can predict the severity of multiple sclerosis

Increased glutamate and deep brain atrophy can predict the severity of multiple sclerosis

WITHDRAWN: The secret behind peripheral inflammation and depression: The hypothalamus

Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation

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