A NOVEL BIOSIGNATURE OF BIPOLAR DISORDER IDENTIFIES SUBJECTS DURING BOTH AFFECTIVE EPISODES AND EUTHYMIA: ROLE OF THE SYSTEMIC‑INFLAMMATORY (SII) INDEX AND OF GENDER DIFFERENCES

Inflammation and immune functions may play a key role in the etiopathogenesis and outcome of Bipolar Disorder (BD), a psychiatric disease with heterogeneous phenotypic manifestations hampering the achievement of a correct diagnosis. We investigated whether variations in specific peripheral biomarkers might be exploited as a reliable BD biosignature. BD-subjects were enrolled during an active phase of the disease, together with healthy controls (CTRL). Complete blood counts, cytokines, and the neurotrophin BDNF were assessed in serum. Rating scales evaluated psychiatric symptoms, global functioning, stress and metabolic comorbidities. All assessments were carried-out at recruitment (T0-active phase) and after 6 months (T1-euthymia). Rating scales showed clear differences between BDs and CTRLs with sex affecting manic and depressive symptoms respectively in BD-women and BD-men at T0. Metabolic comorbidities were more pronounced in BD-men who showed a reduced ability to return to euthymia. The stepwise logistic regression analysis showed that the biosignatures at T0 and at T1 were comparable in their sensitivity (80%) and specificity (77%) to identify BD subjects. BDNF and TNF-alpha were present only at T0, while the T1-biosignature was characterized by a greater inflammatory component and significant sex differences. Interestingly, a novel Systemic Immune‑Inflammatory (SII:[platelets×neutrophils]/lymphocytes) index was the only marker common to both T0 and T1-signatures. Our data suggest that BD-subjects may be identified in each phase of the disease by specific clusters of biological traits dealing with inflammation and brain plasticity, and point to SII as a novel, reliable diagnostic and prognostic biomarker with an elevated translational value. “Bando-Ricerca-Indipendente-ISS20-9286e4091f8e”