Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder

•Persistent inflammation may be associated with reduction of hippocampal and gray matter volumes in older patients with bipolar disorder.•The peripheral sTNF-R1, sIL-2R, and IL-1β levels may link with the neuroinflammation in the brain of bipolar disorder.•Neuroinflammation due to aging, obesity, and pathophysiology of bipolar disorder may play a role in neuroprogression across the life span of bipolar patients. Bipolar disorder (BD) and aging appear to be associated with inflammatory activation. Inflammatory processes might affect hippocampal function, neurogenesis, and gray matter loss. This study investigated the relationship between BD-specific brain regions and the total gray matter volume, peripheral inflammatory markers, and clinical features in older patients with BD. We recruited euthymic patients with bipolar I disorder aged ≥50 years to undergo whole-brain magnetic resonance imaging. Each brain region was divided by an individual's total intracranial volume to obtain that brain region's volume in percentage relative to the total intracranial volume. We measured the plasma levels of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin (IL)-2 receptor (sIL-2R), sIL-6R, IL-1β, and IL-1 receptor antagonist when patients were euthymic. Clinical data were obtained by reviewing available medical records and interviewing patients along with their reliable others. There were 32 patients with a mean age of 61.2 ± 8.3 years and a mean age at illness onset of 33.4 ± 13.8 years in this study. Stepwise regression showed that the right hippocampal volume was negatively associated with the levels of sIL-2R and sTNF-R1. The left hippocampal volume were negatively associated with the sIL-2R level and body mass index. The total gray matter volume had an inverse relationship with sTNF-R1 and IL-1β levels. The duration of bipolar illness, lithium treatment, and antipsychotic use were not associated with hippocampal and total gray matter volumes. It is suggested that persistent inflammation is associated with reduction of hippocampal and gray matter volumes in older patients with BD. This phenomenon is supported by increases in sTNF-R1, sIL-2R, and IL-1β levels. Neuroinflammation due to aging, obesity, and BD pathophysiology may play a role in BD neuroprogression across the life span.