The mediating effect of the striatum-based connectivity on the association between high-sensitivity C-reactive protein and anhedonia in adolescent depression

Nana Liang; Zhenpeng Xue; Wenwen Yu; Xiujuan Yang; Yuejiao Ma; Jianchang Xu; Yumeng Sun; Yuan Shen; Huiyan Li; Jianping Lu; Jianbo Liu

doi:10.1016/j.jad.2025.01.116

The mediating effect of the striatum-based connectivity on the association between high-sensitivity C-reactive protein and anhedonia in adolescent depression

J Affect Disord. 2025 Jan 23:S0165-0327(25)00136-3. doi: 10.1016/j.jad.2025.01.116. Online ahead of print.

Authors

Nana Liang¹, Zhenpeng Xue², Wenwen Yu², Xiujuan Yang¹, Yuejiao Ma², Jianchang Xu², Yumeng Sun², Yuan Shen², Huiyan Li², Jianping Lu³, Jianbo Liu⁴

Affiliations

¹ 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.
² Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Institute of Mental Health, Shenzhen, China.
³ Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Institute of Mental Health, Shenzhen, China. Electronic address: lujianping2018@email.szu.edu.cn.
⁴ Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Institute of Mental Health, Shenzhen, China. Electronic address: jianboliu@aliyun.com.

PMID: 39862985
DOI: 10.1016/j.jad.2025.01.116

Abstract

Background: The potential pairwise connections among high-sensitivity C-reactive protein (hs-CRP), striatum-based circuits, and anhedonia in adolescent depression are not clear. This study aimed to explore whether hs-CRP levels in adolescents with depression influence anhedonia via alterations of striatum-based functional connectivity (FC).

Methods: 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.

Results: 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 DCP_L and right SFG FC negatively predicted anhedonia severity (β = -0.288, p = 0.007). Although hs-CRP levels had no direct effect, 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).

Conclusion: 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.

Keywords: Adolescent depression; Anhedonia; Functional connectivity; High-sensitivity CRP (hs-CRP); Striatum subregions.