Abstract
High levels of peripheral IL-6, a pro-inflammatory cytokine, have been indicated as a key element of the bipolar disorder (BD), allowing to differentiate BD from major depression with high accuracy and to early detect poor responders to antidepressant treatments. IL-6 may contribute to BD pathophysiology through its effects on the neurobiological underpinnings of the disorder, such as grey matter (GM) volumes and resting state functional connectivity (rs-FC) abnormalities. In this study, we primary investigate the relationship between the peripheral plasmatic level of IL-6 and GM volumes, obtained with Voxel-Based Morphometry, in 84 BD inpatients. As secondary aims, we explored if IL-6 levels may be related to self-reported psychopathological dimensions of depression (i.e. symptoms severity and cognitive biases) and seed based rs-FC of brain regions structurally associated with the cytokine. Results showed that higher level of peripheral IL-6 was associated to lower GM volumes in supragenual anterior cingulate cortex, and reduced rs-FC between this area and medial orbito-frontal cortex in BD. Furthermore, in depressed patients IL-6 positively correlated to cognitive biases typically associated to depressive episodes, such as the perceived uncontrollability of negative events, or their generalization across future and situations. Our data provide additional evidence of detrimental effect of systemic inflammation on brain structure in BD and confirm the crucial role of anterior cingulate cortex as neural underpinning of the disorder. However, future studies are needed to replicate our findings in larger samples.