Liang Nana, Xue Zhenpeng, Yu Wenwen, Yang Xiujuan, Ma Yuejiao, Xu Jianchang, Sun Yumeng, Shen Yuan, Li Huiyan, Lu Jianping, Liu Jianbo
State Key Laboratory of Chemical Oncogenomics, Shenzhen Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China; Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Institute of Mental Health, Shenzhen, China.
Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Institute of Mental Health, Shenzhen, China.
J Affect Disord. 2025 May 1;376:497-506. doi: 10.1016/j.jad.2025.01.116. Epub 2025 Jan 23.
The potential pairwise connections among high-sensitivity C-reactive protein (hs-CRP), striatum-based circuits, and anhedonia in adolescents with depressive disorder are not clear. This study aimed to explore whether hs-CRP levels in adolescents with depressive disorder influence anhedonia via alterations of striatum-based functional connectivity (FC).
A total of 201 adolescents (92 with depressive episodes with anhedonia (anDE), 58 with DE without anhedonia (non-anDE), and 51 healthy controls (HCs)) underwent resting-state functional magnetic resonance imaging (fMRI) and completed the anhedonia subscale of the Children's Depression Inventory (CDI). hs-CRP levels were measured from peripheral blood samples in all DE patients.
Compared with HCs, the anDE and non-anDE groups showed increased FC between the left dorsal caudate putamen (DCP_L) and bilateral cerebellum crus I, and decreased FC between the left ventral rostral putamen (VRP_L) and right parahippocampal cortex (PHC) (all p < 0.05). Only the non-anDE group exhibited increased FC between the right visual cortex (VC_R) and left cerebellum VI, VC_R and right fusiform gyrus (FG), and the left visual cortex (VC_L) and right inferior temporal gyrus (ITG) compared to HCs (all p < 0.05). Compared to the non-anDE group, the anDE group showed reduced FC between the VC_R and left cerebellum VI and between the DCP_L and right superior frontal gyrus (SFG) (all p < 0.05). Multiple regression analysis revealed that the FC between DCP_L and right SFG negatively predicted anhedonia severity (β = -0.288, p = 0.007) in the anDE group. Although hs-CRP levels had no direct effect for anhedonia, FC between the DCP_L and right SFG fully mediated the relationship between hs-CRP and anhedonia in the anDE group (effect = 0.184, Bootstrapping 95 % CI = 0.0156, 0.436).
The findings suggest that hs-CRP influences anhedonia through a fully mediated pathway involving alterations in the frontostriatal network, contributing to a greater understanding of the neurobiological mechanisms underlying anhedonia.
抑郁症青少年中，高敏C反应蛋白（hs-CRP）、纹状体相关回路和快感缺失之间潜在的两两关联尚不清楚。本研究旨在探讨抑郁症青少年的hs-CRP水平是否通过改变基于纹状体的功能连接（FC）来影响快感缺失。
共有201名青少年（92名有快感缺失的抑郁发作患者（anDE）、58名无快感缺失的抑郁发作患者（non-anDE）和51名健康对照者（HCs））接受静息态功能磁共振成像（fMRI）检查，并完成儿童抑郁量表（CDI）的快感缺失分量表。对所有抑郁发作患者采集外周血样本测量hs-CRP水平。
与HCs相比，anDE组和non-anDE组左侧背侧尾状壳核（DCP_L）与双侧小脑脚I之间的FC增加，左侧腹侧吻侧壳核（VRP_L）与右侧海马旁皮质（PHC）之间的FC降低（均p<0.05）。与HCs相比，仅non-anDE组右侧视觉皮质（VC_R）与左侧小脑VI、VC_R与右侧梭状回（FG）以及左侧视觉皮质（VC_L）与右侧颞下回（ITG）之间的FC增加（均p<0.05）。与non-anDE组相比，anDE组VC_R与左侧小脑VI之间以及DCP_L与右侧额上回（SFG）之间的FC降低（均p<0.05）。多元回归分析显示，anDE组中DCP_L与右侧SFG之间的FC对快感缺失严重程度具有负向预测作用（β=-0.288，p=0.007）。虽然hs-CRP水平对快感缺失无直接影响，但anDE组中DCP_L与右侧SFG之间的FC完全介导了hs-CRP与快感缺失之间的关系（效应=0.184，Bootstrapping 95%CI=0.0156，0.436）。
研究结果表明，hs-CRP通过涉及额纹状体网络改变的完全介导途径影响快感缺失，有助于更深入了解快感缺失背后的神经生物学机制。
