Patterns of DNA methylation at specific loci of the dopamine transporter 1 gene and psychopathological risk in trios of mothers, fathers and children

ABSTRACT

While accumulating literature is demonstrating the role of the dopamine transporter (DAT) in predicting emotional–behavioural difficulties in adults of at risk populations, only few studies have focused on the possible association between the methylation status of the DAT promoter and the psychopathological risk of mothers, fathers and children in normative samples. The pattern of methylation of M1-M7 loci present in the 5′-untranslated promoter region (5′-UTR) of DAT1, and parental and offspring psychopathological risk were assessed in a sample of 152 families with 5-year-old-children, employing principal components (PCAs) and cluster analyses. Parents’ psychopathological symptoms were assessed through SCL-90/R; children’s emotional-behavioural functioning was evaluated through C-TRF. Cluster analysis allowed to form three clusters; cluster 1 is primarily composed by children with low-/middle-risk profiles; most of children with high-risk are in this cluster, and had parents with mild/high psychopathological risk; children in cluster 2 showed low-risk profiles and their parents had low/mild psychopathological risk; children in cluster 3 were predominantly at middle risk and had parents with low psychopathological risk. Analysis of results shows that DNA methylation occurs in different loci of DAT1 according to patterns of psychopathology and that psychopathological risk is specifically associated with hyper-methylation or hypo-methylation of these loci.

KEYWORDS:

• PCA
• clusters
• methylation
• dopamine transporter
• psychopathological symptoms

Acknowledgements

We thank all the families participating to this study. Special thanks go to Dr. Alessandro Giuliani for help with statistic methodology and interpretation of the results.

Disclosure statement

The authors have one item for conflicts of interest to declare, i.e. the patent: Adriani W., Laviola G., Pascale E., D’Addario C., “METODO PER DETERMINARE IL DEFICIT DI ATTENZIONE CON IPER-ATTIVITÀ”, Italian Patent application (22-DECEMBER-2016) at no. 102016000129938; European patent application (21-DECEMBER-2017) at no. 17830021.6; Publication International Number WO/2018/116228 A1; Holders: Istituto Superiore di Sanità, 50%, Università La Sapienza, 20%; Università di Teramo, 30%.

Additional information

Funding

This study received funds from the ‘Emotional dysregulation as an underpinning mechanism of Attention Problems, Anxiety and Eating Disorders in school-age children: a study on the intergenerational transmission of psychopathological risk and DNA methylation in parents and children’ Sapienza Università di Roma [RG1181643354C478].