Cerebrospinal fluid biomarkers of central nervous system inflammation predict cortical decline in bipolar disorder and ventricular enlargement in healthy controls

Introduction: Bipolar disorder has been associated with significant structural brain changes, potentially driven by central nervous system (CNS) inflammation. This study aimed to investigate the relationship between inflammation biomarkers in cerebrospinal fluid (CSF) and longitudinal structural brain changes.Methods: We included 29 individuals with bipolar disorder and 34 healthy controls, analyzing three selected inflammation-related biomarkers – interleukin-6 (IL-6), interleukin-8 (IL-8), and chitinase-3-like protein 1 (YKL-40) – in both blood serum and CSF. Structural brain changes were assessed through magnetic resonance imaging (MRI) at two time points, focusing on cortical thickness of the middle temporal cortex and inferior frontal gyrus, as well as ventricular volume.Results: In healthy controls, baseline CSF levels of YKL-40 predicted ventricular enlargement in both hemispheres. Among individuals with bipolar disorder, higher baseline levels of IL-8 were associated with a decline in cortical thickness in the right and left middle temporal cortex, as well as the right inferior frontal gyrus. No significant associations were observed with serum biomarkers.Conclusion: These findings suggest that CSF IL-8 may contribute to cortical decline in bipolar disorder. The lack of association between serum biomarkers and brain changes highlights the specificity of CNS inflammation in these processes. Additionally, the observed link between CSF YKL-40 and ventricular enlargement in healthy controls may indicate a role of CNS inflammation processes in normal brain aging.