Neuroinflammation is associated with reduction of hippocampal and gray matter volumes in older patients with bipolar disorder, according to study data published in the Journal of Affective Disorders.

Older adults (≥50 years) in the euthymic phase of bipolar I disorder were recruited to undergo whole-brain magnetic resonance imaging (MRI) for this study. Clinical data were obtained through medical record review and direct interviews with patients and their reliable family members. Affective symptom severity was captured using the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Blood samples were collected at the time of brain scan to measure 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. Brain regions were divided by an individual’s total intracranial volume to obtain regional volume as a percentage of total intracranial volume.

A total of 32 patients were recruited of mean age 61.2±8.3 years and mean age of illness onset 33.4±13.8 years. Duration of bipolar illness, lithium treatment, and antipsychotic use were not associated with hippocampal or total gray matter volumes. Per stepwise regression analyses, right hippocampal volume was negatively associated with age (P =.04) and plasma sIL-2R (P =.03) and sTNF-R1 (P =.01) levels. Left hippocampal volume was negatively associated with sIL-2R level (P =.03) and body mass index (P <.001). Total gray matter volume was negatively associated with IL-1β level (P =.04) and body mass index (P =.002). In addition, higher levels of sTNF-R1 (P =.07) were associated with lower total gray matter volume, suggesting an inverse relationship between total gray matter volume and IL-1β and sTNF-R1 levels.

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As such, inflammation, as indicated by increases in sTNF-R1, sIL-2R, and IL-1β levels, appears to be associated with reductions in hippocampal and gray matter volumes in older patients with bipolar I disorder. Researchers also hypothesized that neuroinflammation related to age, body mass index, and bipolar disorder symptom severity may also affect bipolar disorder progression among older adults.


Tsai S-Y, Gildengers AG, Hsu J-L, Chung K-H, Chen P-H, Huang Y-J. Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder. J Affect Disord. 2019;244:60-66.