Low retinal dehydrogenase 1 (RALDH1) level in prepubertal boys with autism spectrum disorders: a possible link to dopamine dysfunction?
Denis Paval 1, Florina Rad 2, Razvan L. Rusu 3, Alexandru-Stefan Niculae 1, Horatiu A. Colosi 4, Iuliana Dobrescu 2, Eleonora Dronca 3*
1Faculty of Medicine, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy, 2‘Alexandru Obregia’ Psychiatry Hospital, ‘Carol Davila’ University of Medicine and Pharmacy, 3Department of Molecular Sciences, Faculty of Medicine, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy, 4Department of Medical Informatics and Biostatistics, Faculty of Medicine, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy
Received: June 28, 2016; Revised: August 23, 2016; Accepted: September 5, 2016; Published online: September 5, 2016.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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 disorders (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.
Keywords: autism, retinal dehydrogenase, dopamine, 4-hydroxynonenal, glutathione


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