Characterizing Unipolar and Bipolar Depression by Alterations in Inflammatory Mediators and the Prefrontal-Limbic Structural Network

Abstract

Objective. The prefrontal-limbic system is closely associated with emotion processing in both unipolar depression (UD) and bipolar depression (BD). Evidence for this link is derived mostly from task-fMRI studies, with limited support from structural findings. Therefore, this study explores the differences in the emotional circuit in these two disorders on a structural, large-scale network basis, coupled with the highly noted inflammatory and growth factors. Methods. In this study, 31 BD patients, 37 UD patients, and 61 age-, sex-, and education-matched healthy controls (HCs) underwent diffusion-weighted imaging (DWI) scanning and serum cytokine sampling. The study compared cytokine levels and prefrontal-limbic network alterations among the three groups and explored potential biological and neurobiological markers to distinguish the two disorders using graph theory, network-based statistics (NBS), and logistic regression. Results. Compared to BD patients, UD patients showed greater s-100β protein levels, higher efficiency of the right amygdala, and significantly elevated prefrontal-cingulate-amygdala subnetwork intensity. Importantly, the altered prefrontal-cingulate-amygdala subnetwork, nodal efficiency of the right amygdala, IL-8, IL-17, and s-100β levels were risk factors for the diagnosis of UD, whereas anxiety symptoms tended to closely correlate with BD. Moreover, binary logistic regression manifested these factors achieved an area under the curve (AUC) of the receiver operating characteristics (ROC) of 0.949, with 0.875 sensitivity and 0.938 specificity in UD vs. BD classification. Conclusions. These findings narrow the gap in the structural network of emotional circuits in bipolar and unipolar depression, pointing to distinct emotion-processing mechanisms in both disorders.

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review

“…Conflicting results are reported in MDD patients with longer illness duration. An increase in S100B levels [ 60 , 61 , 64 , 65 ], no differences [ 66 , 67 , 68 , 69 , 70 , 71 ], or lower [ 61 , 72 , 73 ] S100B levels in recurrent episodes of MDD compared to HC were found. Rothermundt et al (2001) described a S100B increase in melancholic depression compared to HC and no differences in non-melancholic depression [ 74 ].…”

“…At the whole-brain level, only the MDD group showed differences compared to HC, with significantly enhanced global efficiency, local efficiency, and decreased shortest path length. MDD patients showed higher efficiency of the right amygdala, significantly elevated prefrontal-cingulate-amygdala subnetwork intensity, and higher S100B levels compared to BD patients [ 70 ].…”

“…S100B levels were also studied in the context of cognitive functions [ 10 , 17 , 28 , 45 , 54 , 115 ], event-related potentials [ 64 , 69 , 90 ], neuroimaging [ 11 , 52 , 70 , 72 , 97 , 98 ], and electroconvulsive therapy [ 83 , 85 , 86 , 87 , 88 , 89 ]. Finally, suicidal behavior, regardless of diagnosis status, was investigated concerning its correlation with S100B levels, also with inconsistent results, where no relationships [ 118 ], positive correlation with severity of suicidal ideations [ 119 ], or negative correlation with the number of suicidal attempts [ 43 ] were found.…”

“…In the cross-sectional comparisons of patient groups with healthy controls, most of the studies consistently reported elevated S100B levels in both drug-naïve/drug-free or SCH-medicated patients , but also no differences [34,37,38], or lower S100B, in SCH compared to HC [39,40] were reported. Results of the studies in MDD are more conflicting, with fewer publications concerning first-episode patients [58][59][60][61], showing elevated [58][59][60][61][63][64][65], decreased [61,62,72,73], or no differences [60,61,[66][67][68][69][70][71] in S100B levels compared to HC. In BD, studies are conducted in manic [62,[93][94][95][96] or depressive episodes [77,97,98], as well as in euthymia [71,[99][100][101][102], also with inconsistent results; however, a recent meta-analysis confirmed increased S100B levels in bipolar disorder [120].…”

“…In the study by Lei et al (2023), 31 BD patients, 37 MDD patients, and 61 matched HC underwent diffusion-weighted imaging (DWI). At the whole-brain level, only the MDD group showed differences compared to HC, with significantly enhanced global efficiency, local efficiency, and decreased shortest path length.…”