Evidence map›Paper›PMID 40138886›Full record

ArticleEBioMedicine2025

Cerebrospinal fluid metabolomics in autistic regression reveals dysregulation of sphingolipids and decreased β-hydroxybutyrate.

Jingya Yan, Velda X Han, Hannah F Jones, Timothy A Couttas, Beverly Jieu, F Markus Leweke, Jennifer Lee, Catherine Loi, Richard Webster, Kavitha Kothur and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Sphingolipids in Emotional Well-Being.Journal of neurochemistry · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jingya YanKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, NSW, Australia; Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Velda X HanKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hannah F JonesStarship Hospital, Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
Timothy A CouttasNeuroscience Research Australia, Randwick, NSW, Australia; Brain and Mind Centre, The University of Sydney, NSW, Australia.
Beverly JieuBrain and Mind Centre, The University of Sydney, NSW, Australia.
F Markus LewekeBrain and Mind Centre, The University of Sydney, NSW, Australia.
Jennifer LeeDepartment of Endocrinology, The Children's Hospital at Westmead, NSW, Australia.
Catherine LoiDepartment of Endocrinology, The Children's Hospital at Westmead, NSW, Australia.
Richard WebsterTY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, The University of Sydney, Westmead, New South Wales, Australia.
Kavitha KothurKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, The University of Sydney, Westmead, New South Wales, Australia.
Manoj P MenezesClinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, The University of Sydney, Westmead, New South Wales, Australia.
Jayne AntonyTY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, The University of Sydney, Westmead, New South Wales, Australia.
Tejaswi KandulaDepartment of Neurology, Sydney Children's Hospital Network, Sydney, NSW, Australia.
Michael CardamoneDepartment of Neurology, Sydney Children's Hospital Network, Sydney, NSW, Australia.
Shrujna PatelKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Sushil BandodkarClinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Department of Biochemistry, The Children's Hospital at Westmead, NSW, Australia.
Russell C DaleKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia. Electronic address: russell.dale@health.nsw.gov.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutism is highly heritable, however actionable genetic findings are only found in a minority of patients. Many people with autism suffer loss of neurodevelopmental skills, known as autistic regression. The cause of regression is poorly understood, and the diagnostic and therapeutic pathways are lacking.

methodsWe used untargeted metabolomics using a UPLC-Q-Exactive-HFx Mass Spectrometry to examine cerebrospinal fluid (CSF) from twenty-two patients with autistic regression compared to sixteen controls with neurodevelopmental disorders (but not autistic regression) and thirty-four controls with other neurological disease (headache, encephalitis, epilepsy). The twenty-two patients with autistic regression consisted of two groups: early (infantile) autistic regression <2 years of age (n = 8), and later regression of skills >4 years of age, often in the context of pre-existing developmental concerns (n = 14). Metabolites of interest were then quantified and validated using targeted assays.

findingsUntargeted case-control studies revealed good separation of patients from controls using multivariate analysis. β-hydroxybutyrate was significantly decreased in the CSF of patients with autistic regression, and the findings were validated using a targeted β-hydroxybutyrate assay. The sphingolipid, sphingosine-1-phosphate was significantly elevated in the discovery case-control studies, and sphingolipid metabolism pathways were also significantly dysregulated. We therefore developed a targeted metabolite assay of forty sphingolipids. After FDR correction, 21 of the 40 sphingolipids were significantly dysregulated (p

interpretationOur data shows the potential utility of CSF metabolomics in the context of autistic regression, a clinical syndrome which has historically lacked pathophysiological biomarkers and disease modifying therapies.

fundingFinancial support for the study was granted by Dale NHMRC Investigator grant APP1193648, Petre Foundation, Cerebral Palsy Alliance, and Ainsworth and SCHF Neuroscience grant scheme.

Indexed as

3-Hydroxybutyric AcidAutistic DisorderMetabolomeMetabolomicsSphingolipidsAdolescentBiomarkersCase-Control StudiesChildChild, PreschoolFemaleHumansInfantMale3-Hydroxybutyric AcidBiomarkersSphingolipidsInflammationLipidomicsMetabolomicsNeurodevelopmental disorders

Identifiers

PMID40138886
PMCPMC11986237

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.