Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

Lipids Health Dis. 2021 Aug 26;20(1):93. doi: 10.1186/s12944-021-01522-9.


Background: About 20-40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon.

Methods: A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low-density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents.

Results: Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors.

Conclusions: Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

Keywords: Autistic regression; Cholesterol; Lipid; Retinol binding protein 4; Triglyceride; autism spectrum disorder.

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / blood*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cholesterol / blood
  • Female
  • Humans
  • Lipids / blood*
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Male
  • Patient Acuity
  • Psychiatric Status Rating Scales
  • Retinol-Binding Proteins, Plasma / analysis*
  • Triglycerides / blood


  • Lipids
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • Triglycerides
  • Cholesterol