# Sphingolipids in Emotional Well‐Being

**Authors:** L. S. Kalinichenko, I. Zoicas, C. Mühle, J. Kornhuber, C. P. Müller

PMC · DOI: 10.1111/jnc.70379 · Journal of Neurochemistry · 2026-02-17

## TL;DR

This paper explores how sphingolipids, important components of brain cell membranes, influence emotional well-being and may contribute to mental health and resilience.

## Contribution

The paper highlights sphingolipids as a novel potential mechanism underlying emotional well-being and psychiatric disorders.

## Key findings

- Sphingolipids like ceramides and gangliosides influence neuronal plasticity and brain function.
- Imbalances in sphingolipid metabolism may contribute to psychiatric disorders such as depression and anxiety.
- Sphingolipids are proposed as potential biomarkers for emotional well-being and mental resilience.

## Abstract

Emotional well‐being is a multifactorial concept, which comprises not only life quality of human individuals, but also their mental and physical health. It encompasses several key parameters, many of which have behavioral representation in daily life. These include finding positive meaning of life events, ability to maintain supportive and caring social interactions, reward‐oriented behavior, and many others. It is well‐known that the behavioral phenotype is tightly bound to certain physiological and metabolic factors, among which sphingolipid (SL) balance of the organism and especially central nervous system might play an important role. Recent research proposes that SLs mediate multiple components of emotional well‐being. The most abundant brain SL types, ceramides and gangliosides, dynamically shape the composition of protein carrying cellular membranes and overall neuronal plasticity. Multiple studies show the contribution of SLs to normal brain functioning and corresponding beneficial behavioral phenotypes, such as stress resilience, cognitive performance, and social interactions, which determine emotional well‐being. On the other hand, an imbalance in SL metabolism affects normal functioning of cells and thus contributes to the development of several psychiatric disorders, such as depression, anxiety, cognitive decline, schizophrenia, and others. SLs are suggested as a potentially new mechanism of the key behavioral manifestations of emotional well‐being, which might be further investigated as new biomarkers of life quality as well as physical and mental resilience.

Sphingolipids are essential constituents of neuronal membranes and are increasingly recognized as contributors to the key behavioral manifestations associated with emotional well‐being.

## Linked entities

- **Diseases:** depression (MONDO:0002050), anxiety (MONDO:0005618), schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** Ctss (cathepsin S) [NCBI Gene 13040] {aka Cats}, B4galnt1 (beta-1,4-N-acetyl-galactosaminyl transferase 1) [NCBI Gene 14421] {aka 4933429D13Rik, Gal-NAc-T, GalNAc-T, GalNAcT, Galgt1, Ggm-2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Dcx (doublecortin) [NCBI Gene 13193] {aka Dbct}, Htr2c (5-hydroxytryptamine (serotonin) receptor 2C) [NCBI Gene 15560] {aka 5-HT-1C, 5-HT-2C, 5-HT1C, 5-HT2C, 5-HT2cR, 5-HTR2C}, Chat (choline O-acetyltransferase) [NCBI Gene 290567], NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, Asah1 (N-acylsphingosine amidohydrolase 1) [NCBI Gene 84431] {aka Asah}, Gba1 (glucosylceramidase beta 1) [NCBI Gene 14466] {aka GC, GCase, GLUC, Gba, betaGC}, PRKCE (protein kinase C epsilon) [NCBI Gene 5581] {aka PKCE, nPKC-epsilon}, PLPP2 (phospholipid phosphatase 2) [NCBI Gene 8612] {aka LPP2, PAP-2c, PAP2-g, PPAP2C}, S1pr1 (sphingosine-1-phosphate receptor 1) [NCBI Gene 13609] {aka Edg1, Lpb1, S1p, S1p1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Ormdl2 (ORM1-like 2 (S. cerevisiae)) [NCBI Gene 66844] {aka 0610012C09Rik}, Degs2 (delta 4-desaturase, sphingolipid 2) [NCBI Gene 70059] {aka 2210008A03Rik, DES2}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, GBA1 (glucosylceramidase beta 1) [NCBI Gene 2629] {aka GBA, GCB, GLUC}, Ugcg (UDP-glucose ceramide glucosyltransferase) [NCBI Gene 22234] {aka Epcs21, GlcT-1, Ugcgl}, SMPDL3B (sphingomyelin phosphodiesterase acid like 3B) [NCBI Gene 27293] {aka ASML3B}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, SPTLC3 (serine palmitoyltransferase long chain base subunit 3) [NCBI Gene 55304] {aka C20orf38, LCB 3, LCB2B, LCB3, SPT 3, SPT3}, Rai1 (retinoic acid induced 1) [NCBI Gene 19377] {aka Gt1}, Prkce (protein kinase C, epsilon) [NCBI Gene 18754] {aka 5830406C15Rik, PKC[e], PKCepsilon, Pkce}, Spt (salivary protein cluster) [NCBI Gene 111363], SPHK2 (sphingosine kinase 2) [NCBI Gene 56848] {aka SK 2, SK-2, SPK 2, SPK-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Sms (spermine synthase) [NCBI Gene 20603] {aka Gy, SPMSY, SpmST, gyro}, Cert1 (ceramide transporter 1) [NCBI Gene 68018] {aka 2810404O15Rik, 9230101K08Rik, CERT, Col4a3bp, GPBP}, ELOVL5 (ELOVL fatty acid elongase 5) [NCBI Gene 60481] {aka HELO1, SCA38, dJ483K16.1}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, CERS3 (ceramide synthase 3) [NCBI Gene 204219] {aka ARCI9, LASS3}, Smpd3 (sphingomyelin phosphodiesterase 3, neutral) [NCBI Gene 58994] {aka 4631433G07Rik, Nsm2, fro, nSMase2}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Htr2a (5-hydroxytryptamine (serotonin) receptor 2A) [NCBI Gene 15558] {aka 5-HT-2, 5-HT-2A, E030013E04, Htr-2, Htr2}, Cers6 (ceramide synthase 6) [NCBI Gene 241447] {aka 4732462C07Rik, Lass6, T1L}, ACER2 (alkaline ceramidase 2) [NCBI Gene 340485] {aka ALKCDase2, ASAH3L}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, St3gal5 (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) [NCBI Gene 20454] {aka 3S-T, Siat9, [a]2}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, ASAH2 (N-acylsphingosine amidohydrolase 2) [NCBI Gene 56624] {aka BCDase, HNAC1, LCDase, N-CDase, NCDase}, DEGS1 (delta 4-desaturase, sphingolipid 1) [NCBI Gene 8560] {aka DEGS, DEGS-1, DES1, Des-1, FADS7, HLD18}, Grin1 (glutamate receptor, ionotropic, NMDA1 (zeta 1)) [NCBI Gene 14810] {aka GluN1, GluRdelta1, GluRzeta1, M100174, NMD-R1, NMDAR1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, PRKCD (protein kinase C delta) [NCBI Gene 5580] {aka ALPS3, CVID9, MAY1, PKCD, nPKC-delta}, Asah1 (N-acylsphingosine amidohydrolase 1) [NCBI Gene 11886] {aka 2310081N20Rik, AC, Asah}, St8sia1 (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) [NCBI Gene 20449] {aka 9330109E03Rik, GD3S, Sia-T, Siat8, Siat8a}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, Ntrk1 (neurotrophic tyrosine kinase, receptor, type 1) [NCBI Gene 18211] {aka Tkr, TrkA, trk}, Anxa6 (annexin A6) [NCBI Gene 11749] {aka Anx6, AnxVI, Cabm, Camb}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, ASAH1 (N-acylsphingosine amidohydrolase 1) [NCBI Gene 427] {aka AC, ACDase, ASAH, PHP, PHP32, SMAPME}, MBTPS1 (membrane bound transcription factor peptidase, site 1) [NCBI Gene 8720] {aka CAOP, PCSK8, S1P, SEDKF, SKI-1}, SMPD5 (sphingomyelin phosphodiesterase 5 (pseudogene)) [NCBI Gene 392275] {aka MA-nSMase, SMPD5P}, FADS3 (fatty acid desaturase 3) [NCBI Gene 3995] {aka CYB5RP, LLCDL3}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, CERK (ceramide kinase) [NCBI Gene 64781] {aka LK4, dA59H18.2, dA59H18.3, hCERK}, Cers1 (ceramide synthase 1) [NCBI Gene 93898] {aka Lass1, Uog-1, to}, SMPD3 (sphingomyelin phosphodiesterase 3) [NCBI Gene 55512] {aka NSMASE2}, CERS2 (ceramide synthase 2) [NCBI Gene 29956] {aka L3, LASS2, SP260, TMSG1}, Sort1 (sortilin 1) [NCBI Gene 20661] {aka 2900053A11Rik, Ntr3, Ntsr3}
- **Diseases:** liver cirrhosis (MESH:D008103), autism (MESH:D001321), deviations (MESH:D010262), CPP (MESH:D000073397), traumatic brain injury (MESH:D000070642), developmental arrest (MESH:D006323), CerS (MESH:D000795), neurodegenerative lysosomal storage disorder (MESH:D016464), hippocampal atrophy (MESH:D001284), Anxiety (MESH:D001007), schizophrenia (MESH:D012559), neuroinflammation (MESH:D000090862), dementia with Lewy bodies (MESH:D020961), PSD (MESH:C536311), nonalcoholic fatty liver disease (MESH:D065626), insomnia (MESH:D007319), white matter atrophy (MESH:D000090122), mental disorder (MESH:D001523), SL (MESH:D013106), brain atrophy (MESH:C566985), addiction (MESH:D019966), Alzheimer disease (MESH:D000544), memory decline (MESH:D060825), ischemic (MESH:D002545), SFC (MESH:C000719212), Huntington disease (MESH:D006816), HAM-D (MESH:C538175), alterations (MESH:D004408), anhedonia (MESH:D059445), Sleep (MESH:D012893), ASD (MESH:D000067877), AUD (MESH:D000437), PD (MESH:D010300), inflammation (MESH:D007249), Neurodegeneration (MESH:D019636), metabolic syndrome (MESH:D024821), SLs (MESH:C536329), L1 (MESH:C536029), neuropsychological disorders (MESH:D009358), GM2-gangliosidosis (MESH:D020143), AC (MESH:D055577), Niemann-Pick disease deficient in ASM (MESH:D052556), squamous cell carcinoma (MESH:D002294), MDD (MESH:D003865), BP (MESH:D007022), CUS (MESH:D013313), hyperactivity (MESH:D006948), affective disorders (MESH:D019964), mental health problems (MESH:D000076082), Obesity (MESH:D009765), Niemann-Pick diseases (MESH:D009542), dysrhythmia (MESH:D001145), insulin resistance (MESH:D007333), social dysfunction (MESH:D000067404), mental health (OMIM:603663), impaired social interaction (MESH:C563663), psychosis (MESH:D011618), ADHD (MESH:D001289), cerebral ischemic injury (MESH:D017202), DH (MESH:D000092142)
- **Chemicals:** phosphatidic acid (MESH:D010712), corticosterone (MESH:D003345), sialic acid (MESH:D019158), triacylglycerols (MESH:D014280), paroxetine (MESH:D017374), dihydrosphingosine (MESH:C005682), carbon (MESH:D002244), GM1 (MESH:D005677), choline (MESH:D002794), cortisol (MESH:D006854), glycosphingolipid (MESH:D006028), vincristine (MESH:D014750), glycerophospholipid (MESH:D020404), sugar (MESH:D000073893), ceramide-1-phosphate (MESH:C065576), reserpine (MESH:D012110), O (MESH:D010100), haloperidol (MESH:D006220), fat (MESH:D005223), GD3 (MESH:C026226), SR33557 (MESH:C059901), nitric oxide (MESH:D009569), cholesterol (MESH:D002784), Ceramide (MESH:D002518), b (MESH:D001895), myriocin (MESH:C001996), NA (MESH:D009638), GABA (MESH:D005680), glutamate (MESH:D018698), amphetamine (MESH:D000661), pO (MESH:D011059), ACh (MESH:D000109), sphingosine-1-phosphate (MESH:C060506), GM2 ganglioside (MESH:D005678), GluCer (MESH:D005963), serine (MESH:D012694), acylcarnitines (MESH:C116917), GalCer (MESH:D005699), FDG (MESH:D019788), valproate (MESH:D014635), hydrocarbon (MESH:D006838), fatty acid (MESH:D005227), carbohydrate (MESH:D002241), selenium (MESH:D012643), sulfatides (MESH:D013433), fumonisin B1 (MESH:C056933), dihydroceramide (MESH:C109343), Cocaine (MESH:D003042), Ganglioside (MESH:D005732), ceramide phosphoethanolamine (MESH:C060281), lysophospholipid (MESH:D008246), AMPA (MESH:D018350), ethanolamine (MESH:D019856), D-PDMP (MESH:C033110), lactosylceramides (MESH:D007790), Cer20:0 (-), SM (MESH:D013109), melatonin (MESH:D008550), 5-HIAA (MESH:D006897), GW4869 (MESH:C468773)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Cercopithecidae (monkey, family) [taxon 9527], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Mutations:** rs4668077, rs2099527, rs143078230, serine residues 896, rs139609178, A53T, rs398607, rs35785620, rs2574985, rs1805078
- **Cell lines:** CHO — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_0213), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), /6Cr — Homo sapiens (Human), Alpha-1 antitrypsin deficiency, Induced pluripotent stem cell (CVCL_C934), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), Hela — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), CHO-K1 — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_0214)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12910332/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12910332/full.md

## References

390 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910332/full.md

---
Source: https://tomesphere.com/paper/PMC12910332