Mood Disorders and Inflammatory Markers: Pathophysiology and Implications for Treatment

INTRODUCTION: Mood disorders are chronic disorders, responsible for disability worldwide. In recent years a growing body of literature has proposed a psycho-neuro-immunological hypothesis, according to which inflammation may play a role in the development and response to treatment of such diseases. Both Major Depressive Disorder and Bipolar Disorder have been associated with peculiar patterns of cytokine alterations and, on the other hand, some psychotropic drugs showed the ability to affect cytokines production, making an immunomodulatory action of these drugs plausible. METHODS: Our research also included a comparison of Neurokinin-1Receptor (NK-1R) expression and Substance P (SP) ability to induce NF-κB activation in monocytes from BD patients and healthy donors (HD). A further study was conducted on human monocytes, which were used as such or differentiated into M1 and M2 macrophages. Cells were treated with vortioxetine before or after differentiation, and their responsiveness, in terms of included oxy-radical and TNFα production, TNFα and PPARγ gene expression, and NF-κB translocation was evaluated. RESULTS: An increase in pro-inflammatory cytokines such as IL-4, TNF-α, soluble interleukin-2receptor (sIL2-R), IL-1β, IL-6, soluble receptor of TNF-alpha type1 (STNFR1) and C-reactive protein (CRP) is reported in BD patients, during all phases of the disease. IL‐1β, IL‐6, and TNF‐α serum levels are elevated and an increased microglial activation can be observed in some brain regions in MDD patients. NK-1R expression showed relevant alterations in BD patients and SP involvement appeared plausible. Vortioxetine showed anti-inflammatory effect. CONCLUSIONS: Neuro-immunomodulation must be taken into consideration when dealing with the pathophysiology of psychiatric disorders and in the choice of antidepressants; the effect of medications affecting the serotoninergic pathway on the innate immune system should be further investigated, also in a disease-specific context