Targeting inflammation to influence mood following spinal cord injury: a randomized clinical trial

David J. Allison, David S. Ditor

The purpose of the present study was to examine the efficacy of targeting inflammation as a means of improving mood following spinal cord injury (SCI) and explore the potential mechanisms of action. The study was a randomized, parallel-group, controlled, clinical trial (NCT02099890) whereby 20 participants with varying levels and severities of SCI were randomized (3:2) to either the treatment group, consisting of a 12-week anti-inflammatory diet, or control group. Outcome measures were assessed at baseline, 1 and 3 months, and consisted of CES-D scores of depression, markers of inflammation as assessed by various pro- and anti-inflammatory cytokines and several amino acids related to depression. A significant group × time interaction was found for CES-D (Center for Epidemiologic studies Depression Scale) score (p = 0.01), the TRP/LNAA (tryptophan/large neutral amino acid) ratio (p = 0.04), the composite score of pro-inflammatory cytokines (p = 0.04), IL-1β (interleukin-1 beta) (p = 0.04), and IFN-γ (interferon gamma) (p = 0.03). Pearson's r correlation showed significance between the ∆IL-1β and both the ∆CES-D score (r = 0.740, p < 0.01) and the ∆KYN/TRP (kynurenine/tryptophan) ratio (r = 0.536, p = 0.02). The ∆KYN/TRP ratio was also significantly correlated with the ∆CES-D score (r = 0.586, p = 0.01). Mediation analysis showed that the relationship between the ∆KYN/TRP ratio and the ∆CES-D score was mediated by the ∆IL-1β. Subgroup analysis showed that participants with high CES-D scores had significantly higher concentrations of IL-1β, and all correlations were maintained or strengthened within this subgroup. Overall, the results demonstrated the effectiveness of targeting inflammation as a means of improving mood in SCI, with potential mechanisms relating to the reduction in IL-1β and improvements in levels of neuroactive compounds related to the kynurenine pathway. Due to the limited sample size, results should be interpreted with caution; however, they are worthy of further examination due to the potential impact of inflammation on depression. ClinicalTrials.gov ID: NCT02099890 .