Clin Psychopharmacol Neurosci.  2017 Aug;15(3):229-236. 10.9758/cpn.2017.15.3.229.

Low Retinal Dehydrogenase 1 (RALDH1) Level in Prepubertal Boys with Autism Spectrum Disorder: A Possible Link to Dopamine Dysfunction?

Affiliations
  • 1Department of Molecular Sciences, Faculty of Medicine, Iuliu HaÅ£ieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. eleonora.dronca@umfcluj.ro
  • 2Alexandru Obregia Psychiatry Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  • 3Department of Molecular Sciences, Faculty of Medicine, Iuliu HaÅ£ieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • 4Department of Medical Informatics and Biostatistics, Faculty of Medicine, Iuliu HaÅ£ieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Abstract

OBJECTIVE: Retinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorder (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients. To further assess the detoxification function of RALDH1, we also explored 4-hydroxynonenal protein adducts (4-HNE PAs) and reduced glutathione (GSH) levels. Moreover, considering the effect of testosterone on RALDH1 expression, we measured the second to fourth digit ratio (2D:4D ratio) for both hands, which reflects exposure to prenatal testosterone.
METHODS
Male patients with ASD (n=18; age, 62.9±4.3 months) and healthy controls (n=13; age, 78.1±4.9 months) were examined. Erythrocyte RALDH1, serum 4-HNE PAs and erythrocyte GSH levels were measured using colorimetric assays, and digit lengths were measured using digital calipers.
RESULTS
We found significantly lower (−42.9%) RALDH1 levels in autistic patients as compared to controls (p=0.032). However, there was no difference in 4-HNE PAs levels (p=0.368), GSH levels (p=0.586), or 2D:4D ratios (p=0.246 in the left hand, p=0.584 in the right hand) between healthy controls and autistic subjects.
CONCLUSION
We concluded that a subset of autistic patients had a low RALDH1 level. These results suggest that low RALDH1 levels could contribute to the autistic phenotype by reflecting a dopaminergic dysfunction.

Keyword

Autistic disorder; Retinal dehydrogenase; Dopamine; 4-Hydroxy-2-nonenal; Glutathione
Full Text Links
  • CPN
Share
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr