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Related Experiment Video

Updated: Jan 9, 2026

Author Spotlight: Understanding Adolescent Social Adversity Effects on Neurodevelopment in Mice
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Structure-function coupling alterations in adolescent depression correlate with neurotransmitter systems and

Peiyi Wu1, Ziyi Wang2, Caijiu Deng1

  • 1Department of Psychiatry, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, Liaoning, China.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|December 4, 2025
PubMed
Summary
This summary is machine-generated.

Adolescent major depressive disorder (AMDD) shows altered brain connectivity, linked to neurotransmitters and specific gene expression in neurons and glial cells. These findings may guide new depression treatments.

Keywords:
AdolescentCell-type specificityMajor depression disorderNeuroimagingStructural-functional couplingTranscriptomics

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Adolescent major depressive disorder (AMDD) pathophysiology is unclear, despite occurring during critical brain development.
  • Understanding structural-functional brain coupling (SC-FC coupling) is key to elucidating AMDD mechanisms.

Purpose of the Study:

  • Investigate SC-FC coupling alterations in AMDD.
  • Examine the relationship between SC-FC coupling, neurotransmitter systems, and molecular profiles in adolescents with depression.

Main Methods:

  • Multimodal neuroimaging (DTI, resting-state fMRI) and clinical assessments were used in 107 adolescents with AMDD and 78 controls.
  • Analyzed SC-FC coupling abnormalities, neurotransmitter associations, and gene expression profiles using Allen Human Brain Atlas and BrainSpan data.
  • Performed cell-type enrichment analysis to identify specific cell lineages involved in coupling alterations.

Main Results:

  • AMDD exhibited default mode network decoupling and somatomotor network hypercoupling, with diagnostic potential (AUC=0.83-0.85).
  • Coupling alterations correlated with symptom severity and were associated with dopaminergic and serotonergic systems.
  • Transcriptomic analysis revealed distinct gene expression profiles linked to neuronal (decoupled) and glial (hypercoupled) cell types.

Conclusions:

  • SC-FC alterations in AMDD are associated with neurotransmitter systems and cell-type-specific gene expression.
  • These findings highlight developmentally sensitive mechanisms in adolescent depression.
  • Potential to inform age-appropriate intervention strategies for AMDD.