Rossi S, et al. – The present study was designed to investigate the inflammatory processes in the pathogenesis of psychiatric symptoms and the prognostic value of psychiatric comorbidities in multiple sclerosis (MS). Even though not clinically apparent, mood alterations were induced by intrathecal inflammation and were able to predict inflammatory reactivations in relapsing–remitting (RR) MS. Thus, inflammation was a biological event, not less important than the traditional psychosocial factors, involved in mood disorders.

• In this study, 405 patients with relapsing-remitting (RR) MS underwent a psychiatric evaluation by means of Beck Depression Inventory II (BDI-II) and State/Trait Anxiety Inventory (STAI-Y).
• The researchers evaluated the inflammatory activity level by MRI.
• CSF levels of proinflammatory cytokines were determined in a subset of 111 treatment-naive patients.
• They performed correlation and regression analyses to determine associations between variables.

• Compared with remitting patients, relapsing patients demonstrated greater values of STAI-state and BDI-II but comparable trait-anxiety scores.
• No significant differences in psychometric parameters were found between relapsing and asymptomatic MRI-active patients, highlighting the effect of subclinical inflammation on mood disturbances.
• Along with the subsiding of neuroinflammation, a significant reduction of STAI-state and BDI-II scores was recorded.
• While tumor necrosis factor-α and interleukin-1β correlated with BDI-II, interleukin-2 CSF levels were found to correlate with STAI-state.
• Variations of the psychometric profile were able to detect subclinical reactivation earlier because emotional disorders correlated with subclinical inflammation.
• In accordance with this, high STAI-state values considerably anticipated the possibility of disease reactivation.