ReviewMolecular psychiatry2026
The role of sphingolipids in major depressive disorder and associated cognitive impairment: interactions with monoaminergic signaling, neuroinflammation, and neurogenesis.
Review in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Major depressive disorder (MDD) represents a leading cause of disability. Despite decades of research focused on monoaminergic dysregulation, the exact pathophysiological mechanisms underlying MDD remain incompletely understood. This gap in knowledge has contributed to suboptimal therapeutic outcomes, with approximately one-third of MDD patients showing resistance to conventional treatments. Recent advances in lipidomics support that sphingolipids-including ceramides, sphingomyelins, and their metabolites-could play important roles in depression pathophysiology. This review examines the role of sphingolipid dysregulation in MDD and associated cognitive impairment, with a particular focus on interactions with neurogenesis and apoptosis, monoaminergic signaling, neuroinflammation, mitochondrial dysfunction and oxidative stress, glutamatergic signaling, and synaptic plasticity. Several clinical studies demonstrate altered sphingolipid profiles in MDD patients, with elevated ceramide levels correlating with depression severity. Preclinical evidence supports potential causal relationships between sphingolipid alterations and depressive behaviors through effects on neurotransmission, neuroplasticity, neurogenesis, mitochondrial function, and inflammatory processes. Many established antidepressants influence sphingolipid metabolism through distinct mechanisms-acting directly as functional inhibitors of acid sphingomyelinase (ASM) or modulating this pathway indirectly. This mechanistic convergence positions sphingolipid dysregulation as a potential central mediating node across major pathophysiological pathways in MDD and as a common pathway through which key risk factors may converge, potentially explaining its biological heterogeneity. Sphingolipid metabolism also offers a potential mechanistic explanation for the frequently observed cognitive deficits in MDD. This review synthesizes current evidence regarding sphingolipid involvement in depression pathophysiology and outlines promising avenues for personalized medicine through biomarker development and sphingolipid-targeted therapeutics.
Identifiers
42129477What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.