Abstract
BackgroundPrevious individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD.MethodsIn this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed.ResultsCompared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels.ConclusionsOur results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.
Highlights
Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD)
There were no significant differences in the rate of metabolic syndrome between BD and UD patients
Among the 72 patients with BD, 11 (15.3%) patients were treated with lithium or valproic acid only, 18 (25%) patients were treated with atypical antipsychotics only, 36 (50%) patients were treated with lithium or valproic acid plus atypical antipsychotics, and 7 (9.7%) patients were treated with other medications including lamotrigine and carbamazepine
Summary
Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). Few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD. Increased expressions of inflammatory mediators in depressed patients may lead to a poor response to antidepressant drug therapy [1], affecting brain signaling patterns, cognition, and the production of a constellation of symptoms, termed “sickness behavior” [11, 12]. Pro-inflammatory cytokines have unique and specific actions on neurons and circuits within the central nervous system, influencing the microglial activation [15], signaling molecules in neurotransmission, memory, and glucocorticoid function, as well as activity control [16]. Inflammatory mediators may alter monoamine and glutamate neurotransmissions, glucocorticoid receptor resistance, and hippocampal neurogenesis [17]
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