Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis
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Abstract
Objective: To explore the inflammatory processes in the pathogenesis of psychiatric symptoms and the prognostic value of psychiatric comorbidities in multiple sclerosis (MS).
Methods: Four hundred five patients with relapsing-remitting (RR) MS underwent psychiatric evaluation by means of Beck Depression Inventory II (BDI-II) and State/Trait Anxiety Inventory (STAI-Y). The inflammatory activity level was assessed by MRI. In a subset of 111 treatment-naive patients, CSF levels of proinflammatory cytokines were determined. Correlation and regression analyses were performed to determine associations between variables.
Results: Relapsing patients demonstrated greater values of STAI-state and BDI-II compared with remitting patients but comparable trait-anxiety scores. There were no significant differences in psychometric parameters between relapsing and asymptomatic MRI-active patients, highlighting the effect of subclinical inflammation on mood disturbances. A significant reduction of STAI-state and BDI-II scores was recorded, along with the subsiding of neuroinflammation. Interleukin-2 CSF levels were found to correlate with STAI-state, while tumor necrosis factor-α and interleukin-1β correlated with BDI-II. Because emotional disorders were associated with subclinical inflammation, variations of the psychometric profile were able to detect subclinical reactivation earlier. In line with this, high STAI-state values considerably predicted the possibility of disease reactivation.
Conclusions: Mood alterations are induced by intrathecal inflammation, even though not clinically apparent, and are able to predict inflammatory reactivations in RRMS. Inflammation is therefore a biological event, not less important than the traditional psychosocial factors, involved in mood disorders.
GLOSSARY
- ANOVA=
- analysis of variance;
- BDI-II=
- Beck Depression Inventory–Second Edition;
- COPE-NVI=
- Coping Orientation for Problem Experiences–New Italian Version;
- EDSS=
- Expanded Disability Status Scale;
- HPA=
- hypothalamic-pituitary-adrenal;
- IAS=
- Interaction Anxiousness Scale;
- IL=
- interleukin;
- MS=
- multiple sclerosis;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SLE=
- stressful life event;
- STAI=
- State-Trait Anxiety Inventory;
- TNF-α=
- tumor necrosis factor-α
Footnotes
↵* These authors contributed equally to this work as first authors.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received November 16, 2016.
- Accepted in final form June 13, 2017.
- © 2017 American Academy of Neurology
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