Characterization of Chemokine Receptor Expression in CD8+ T Lymphocytes in Bipolar Disorder

Bipolar Disorder (BD) is a chronic mood disorder whose underlying biological mechanisms remain incompletely understood. Increasing evidence suggests that immune dysregulation may contribute to its pathophysiology. In particular, alterations involving T lymphocytes and the migration of CD8+ T cells toward the central nervous system have been proposed as potentially relevant mechanisms. Similar immune-cell trafficking mechanisms are well characterized in multiple sclerosis, where chemokine receptors and leukocyte adhesion molecules contribute to lymphocyte recruitment and migration across the vascular endothelium.

The aim of the SPERLIC study is to characterize the expression profile of molecules involved in CD8+ T-cell trafficking in individuals with Bipolar Disorder and to compare these profiles with those observed in healthy controls. The study will primarily investigate the chemokine receptors CCR5 and CXCR3, which are involved in CD8+ T-cell recruitment toward the central nervous system. Expression of the adhesion-related molecules PSGL-1, VLA-4, and LFA-1 will also be evaluated. Secondary analyses will investigate possible differences in the expression of CCR5, CXCR3, PSGL-1, VLA-4, and LFA-1 according to the current mood phase, comparing patients experiencing a depressive episode with those experiencing a manic or hypomanic episode.

The study will include individuals aged 25 to 35 years with a diagnosis of Bipolar I or Bipolar II Disorder who are either drug-naive or have been free from psychopharmacological treatment for at least 6 months, together with a group of healthy controls. Patients will be recruited among individuals receiving care at the Psychiatry Unit of the University Hospital "G. Rodolico-San Marco" in Catania, Italy. Healthy controls will be recruited among volunteers without clinical evidence of Bipolar Disorder and without current psychotropic treatment. Clinical characterization will include demographic and clinical variables and standardized psychopathological assessments, including the Hamilton Depression Rating Scale, Mania Rating Scale, and SCL-90.

Peripheral blood samples will be used to isolate peripheral blood mononuclear cells by density-gradient centrifugation. CD8+ T lymphocytes will subsequently be purified using magnetic cell separation. Total RNA will be extracted from purified CD8+ T cells, and the relative mRNA expression of CCR5, CXCR3, PSGL-1, VLA-4, and LFA-1 will be quantified using SYBR-based one-step real-time PCR.

The planned sample comprises 172 participants, equally distributed between individuals with Bipolar Disorder and healthy controls. The sample size was estimated assuming an independent two-sided t-test, an effect size of 0.5, an alpha level of 0.05, and a statistical power of 0.90. Relative gene-expression differences will be calculated using the 2^-ΔΔCt method, and ΔCt values will be used for between-group statistical comparisons.