Scholarlink

<p>Major depressive disorder (MDD) involves multiscale alterations ranging from molecular signaling to large-scale brain network dysfunction. However, how molecular topography constrains system-level connectome reorganization remains inadequately understood, limiting the development of biologically grounded diagnostic markers. We established a biologically grounded framework by integrating molecular organization with systems-level connectome analysis to characterize and classify MDD. Using resting-state functional magnetic resonance imaging data from a discovery cohort of 237 first-episode, medication-naïve MDD patients and 305 healthy controls (HC), as well as an independent multi-site validation cohort comprising 243 MDD patients and 340 HCs, we systematically mapped connectome-wide reconfigurations onto 14 normative neurotransmitter receptor and transporter density distributions. Our findings revealed widespread connectivity alterations (6.38% of edges). These alterations spatially correlated with normative densities of serotonin 1A (5-HT<sub>1A</sub>; <i>ρ</i> = −0.217) and dopaminergic markers, including the dopamine transporter (DAT) and dopamine receptors (D1 and D2; <i>ρ</i> range: −0.204 to −0.227). To translate these mechanistic insights into individual-level predictions, we developed the Neurotransmitter Transporter/Receptor-Annotated Connectome Classification Model (NTR-CCM), which incorporates molecular maps as biological priors to guide feature selection. The NTR-CCM achieved superior diagnostic performance in the discovery cohort (area under the curve [AUC] = 0.83–0.86) and maintained robust generalization in the external validation cohort (AUC = 0.73–0.75). These results indicate that macroscale connectome reorganization in MDD is spatially constrained by the brain’s underlying neurochemical architecture. By bridging molecular and systems scales, the NTR-CCM provides a high-performing and mechanistically interpretable framework for precision psychiatry.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Bridging molecules and connectome: network biomarkers guided by neurotransmitter architecture in major depressive disorder

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月13日

查看全文
  • Qiuyu Lv,
  • Daifeng Dong,
  • Shulin Fang,
  • Xuanyi Wang,
  • Pan Lin,
  • Jianfeng Feng,
  • Qiang Luo,
  • Xiang Wang

摘要

Major depressive disorder (MDD) involves multiscale alterations ranging from molecular signaling to large-scale brain network dysfunction. However, how molecular topography constrains system-level connectome reorganization remains inadequately understood, limiting the development of biologically grounded diagnostic markers. We established a biologically grounded framework by integrating molecular organization with systems-level connectome analysis to characterize and classify MDD. Using resting-state functional magnetic resonance imaging data from a discovery cohort of 237 first-episode, medication-naïve MDD patients and 305 healthy controls (HC), as well as an independent multi-site validation cohort comprising 243 MDD patients and 340 HCs, we systematically mapped connectome-wide reconfigurations onto 14 normative neurotransmitter receptor and transporter density distributions. Our findings revealed widespread connectivity alterations (6.38% of edges). These alterations spatially correlated with normative densities of serotonin 1A (5-HT1A; ρ = −0.217) and dopaminergic markers, including the dopamine transporter (DAT) and dopamine receptors (D1 and D2; ρ range: −0.204 to −0.227). To translate these mechanistic insights into individual-level predictions, we developed the Neurotransmitter Transporter/Receptor-Annotated Connectome Classification Model (NTR-CCM), which incorporates molecular maps as biological priors to guide feature selection. The NTR-CCM achieved superior diagnostic performance in the discovery cohort (area under the curve [AUC] = 0.83–0.86) and maintained robust generalization in the external validation cohort (AUC = 0.73–0.75). These results indicate that macroscale connectome reorganization in MDD is spatially constrained by the brain’s underlying neurochemical architecture. By bridging molecular and systems scales, the NTR-CCM provides a high-performing and mechanistically interpretable framework for precision psychiatry.