Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis

Neurology. 2017 Sep 26;89(13):1338-1347. doi: 10.1212/WNL.0000000000004411. Epub 2017 Aug 25.


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.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Anxiety / complications
  • Anxiety / diagnostic imaging
  • Anxiety / drug therapy
  • Anxiety / immunology*
  • Brain / diagnostic imaging
  • Brain / immunology
  • Comorbidity
  • Depression / complications
  • Depression / diagnostic imaging
  • Depression / drug therapy
  • Depression / immunology*
  • Disability Evaluation
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-1beta / cerebrospinal fluid
  • Interleukin-2 / cerebrospinal fluid
  • Linear Models
  • Logistic Models
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / psychology*
  • Multivariate Analysis
  • Psychiatric Status Rating Scales
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid


  • Anti-Inflammatory Agents
  • IL1B protein, human
  • IL2 protein, human
  • Interleukin-1beta
  • Interleukin-2
  • Tumor Necrosis Factor-alpha