Oligodendrocyte lineage cells dysfunction in depression: early life stress, adolescent vulnerability and the emerging role of lipid metabolism

TL;DR

This paper explores how oligodendrocyte lineage cells may contribute to depression, especially in adolescents, and how early life stress and lipid metabolism play a role.

Contribution

Highlights the novel role of oligodendrocyte lineage cells and lipid metabolism in depression, particularly in developmental vulnerability.

Findings

Oligodendrocyte lineage cells have non-myelinating roles in depression pathology.

Early life stress impacts oligodendrocyte development and increases depression risk.

Lipid metabolic dysregulation is a potential contributor to depression.

Abstract

Depression, as a serious global public health issue, is exhibiting an increasing incidence among younger populations, particularly adolescents, who face unique diagnostic challenges and poorer prognoses. Despite extensive studies on monoaminergic dysfunction, neuroinflammation, and synaptic deficits, its pathophysiological mechanisms remain incompletely understood, particularly in relation to developmental stage-specific vulnerabilities. Oligodendrocyte (OL) lineage cells have recently emerged as potential contributors to depression pathology, not only through their myelinating roles but also via non-myelinating functions, such as metabolic support, neuroimmune interaction, and circuit modulation. Early life represents a critical development window characterized by rapid proliferation, differentiation, and lipid synthesis of oligodendrocyte precursor cells, during which these cells are highly susceptible to environmental stressors. Such developmental susceptibility may underlie the long-lasting impact of early life stress (ELS) contribute to depression risk across the lifespan. This review summarizes recent advances in understanding the myelinating and non-myelinating functions of OL lineage cells related to depression pathology, with particular emphasis on their developmental vulnerability to ELS and potential contribution of lipid metabolic dysregulation. We further review emerging pharmacological and non-pharmacological strategies targeting OL lineage cells as potential therapeutic methods.

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