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Association of pro-inflammatory cytokines with serum levels of fatty acid in patients with PTSD − a cohort study

Background: Two main types of polyunsaturated fatty acids (PUFA) are omega-6 and omega-3 PUFA. An increasing literature provide evidence that serum omega-3 PUFA levels are associated with the physiopathology of psychiatric disorders[1], with the reduction of inflammation being proposed as one of the mechanisms[2]. Eicosapentaenoic acid (EPA), a member of the omega-3 PUFA, has been reported to have anti-inflammatory properties while omega-6 PUFA, that can be converted into arachidonic acid (AA) has pro-inflammatory properties. Increased levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) have been found in patients with posttraumatic stress disorder (PTSD) [3]. Aims: To investigate the associations between serum PUFA composition and pro-inflammatory cytokines levels in participants suffering from PTSD, at baseline and after 12 weeks of supplementation with omega-3 PUFA. Methods: The present study included 26 Croatian Homeland war veterans, diagnosed with chronic PTSD and without major comorbidities, who were treated with stable dose of sertraline over a three-month treatment period. Levels of pro-inflammatory cytokines (TNF- α, IL-6, and IL-1β) were determined by the enzyme- linked immunosorbent assay method. Fatty acids levels were measured at once after all blood samples have been collected. Gas chromatography was performed on SRI 8610C Gas chromatograph (SRI Instruments Chromatography Systems, Torrance, CA, USA) and the composition of fatty acid methyl esters was analyzed by a validated ISO method 5508:1990(E). Severity of PTSD symptomatology was assessed by Clinician- Administered PTSD Scale (CAPS), Hamilton Anxiety Scale (HAM-A) and 17-item Hamilton Depression Scale (17-HAM-D). During 12 weeks the participants were taking both omega-3 capsules (600mg/day) and the sertraline therapy. The study outcomes were measured at baseline and after 12 weeks. Kendall tau correlation analysis and one sample signed test were used in data analysis. Results: At baseline, cytokine levels were not associated with the serum composition of omega-3 PUFA (P≥0.125 for associations with total omega-3, EPA, or DHA levels), and similar results were found after 12 weeks of omega-3 supplementation (P≥0.127). On the other hand, AA and AA/EPA levels demonstrated a weak association with IL-6 level at the baseline (τ=0.277, P=0.096 for both ; significant at 0.1 level), but not at the end of a study. After 12 weeks of supplementation total omega-3, EPA and DHA serum levels increased (fold increase, P≤0.001), whereas AA/EPA levels decreased (P≤0.001). In addition, the severity of PTSD symptoms at the end of the study significantly decreased, on average by 8 to 13% on the psychometric scales per person (P<0.001 for all). Conclusion: Although we showed that 12-weeks of omega-3 PUFA supplementation affected the serum composition of FA in a favorable way and that the severity of PTSD was reduced, no association between the omega-3 and the tested cytokine levels was identified in a study. The only potential association was found for AA at baseline. The findings indicate that, in these chronic patients suffering from PTSD for at least 20 years, the inflammatory response mediated by FA might be restrained to a certain degree, particularly with regard to protective mechanisms that are mediated by omega-3 PUFA. References [1] Prior, P.L. , Galduróz, J.C. , 2012. (N-3) Fatty acids: molecular role and clinical uses in psychiatric disorders. Adv Nutr 3(3), 257-265. [2] Shelton, R.C. , Miller, A.H. , 2010. Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Prog Neurobiol 91(4), 275–299. [3] Passos, I.C. , Vasconcelos M.M.P. , Cost, L.G. , Kunz, M. , Brietzke, E. , Quevedo, J. , et al. , 2015. Inflammatory markers in *post- traumatic* *stress* disorder: a systematic review, meta- analysis, and meta-regression. Lancet Psychiatry 2(11), 1002-1012.

pro-inflammatory cytokines ; fatty acid ; PTSD

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