A retrospective comparative study: Novel diagnostical markers of inflammation and cardiovascular risk for bipolar disorder and manic episodeRunning Title: Novel inflammatory markers in bipolar disorder

Objective Pan-immune inflammation value (PIV),inflammation burden index (IBI) and atherogenic index of plasma (AIP), neutrophil/ high-density lipoprotein (HDL) raito (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR) and platelet/HDL ratio (PHR) have been recently investigated as novel inflammatory and cardiovascular markers. The aim of our study was to compare these indices with the manic episode and remission period of bipolar disorder (BD) patients with controls and to investigate the relationship between these indices and the clinical characteristics of the patients and whether these indices can be biomarkers for the disease and manic episode. Methods In this retrospective observational study, data were collected from 66 patients in remission, 67 patients in manic episode and 70 controls. Differences in PIV, IBI, AIP, NHR, MHR, LHR and PHR were analyzed, logistic regression analysis was performed to identify predictors of manic episodes, and the diagnostic potential of these parameters was evaluated using ROC curves. Results Significant differences were found between the three groups in NHR (p<0.001), MHR (p=0.001), LHR (p=0.013), AIP (p<0.001), PIV (p<0.001) and IBI (p<0.001). IBI (p<0.001) and PIV (p:0.001) were found to be positive predictors of manic episode. ROC analysis showed that IBI (p<0.001) and PIV (p<0.001) can be used to define manic episode; IBI (p<0.001), PIV (p<0.001) and AIP (p:0.001) can be used to define BD. Conclusion Given the inflammatory and atherogenic processes in the etiopathogenesis, the novel biomarkers PIV, IBI and AIP may be promising therapeutic targets for BD. In addition, these biomarkers can be used as easily accessible, inexpensive clinical tools to predict illness, manic episode and severity of manic episode.