Neuregulin-1 mRNA Levels Downregulated in Autism Spectrum Disorder and Linked to Executive Function Deficits
In a large study of 1,540 ASD patients and 1,490 controls, quantitative RT-PCR of peripheral blood revealed significant downregulation of all three NRG1 mRNA types in ASD patients. The expression changes correlated with deficits in working memory, response inhibition, and vigilance, as well as with ASD symptom severity. These findings suggest NRG1 as a potential peripheral biomarker and therapeutic target in autism.
The original study
Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.
- Authors
- Abbasy S, Shahraki F, Haghighatfard A, Qazvini MG, Rafiei ST, Noshadirad E, et al.
- Journal
- EBioMedicine
- Type
- Clinical Trial, Journal Article
- PMID
- 30415889
Original abstract
BACKGROUND: Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia. METHODS: mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQ > 70) and 1490 control children by quantitative Real Time PCR. Also three domains of executive functions (working memory, response inhibition and vigilance) were examined in all subjects. FINDINGS: All three types were significantly down regulated in ASD patients. Significant deficiencies in executive functions (EF) were found in ASD patients. EF deficiencies mostly were associated with down expression of mRNA level of types I and III. Also correlations were found between NRG1 expression with gender and severity of ASD symptoms. INTERPRETATIONS: Findings primarily have been suggested involvement of NRG1 in etiology of ASD. Also correlation of NRG1 mRNA level with EF deficiencies could shed lights on EF mechanisms and may suggest targeted treatments to improve particular executive functions. FUND: Young researchers and elites club funded the project due to the annual grant of special talents of Club that gave to Arvin Haghighatfard.