The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels

ABSTRACT

Objectives

Vitamin D deficiency has been associated with psychiatric disorders and behavioral phenotypes such as Attention-Deficit/Hyperactivity Disorder (ADHD). Considering that vitamin D levels are polygenic, we aim to evaluate the overall effects of its genetic architecture on symptoms of inattention, hyperactivity, and impulsivity and on the serum levels of vitamin D in two independent samples of adults, as well as the specific effects of five relevant polymorphisms in vitamin D-related genes.

Methods

We evaluated 870 subjects from an ADHD sample (407 cases and 463 controls) and 319 subjects from an academic community (nutrigenetic sample). Vitamin D serum levels were obtained through Elisa test and genetic data by TaqMan™ allelic discrimination and Infinium PsychArray-24 BeadChip genotyping. Polygenic Scores (PGS) were calculated on PRSice2 based on the latest GWAS for Vitamin D and statistical analyses were conducted at Plink and SPSS software.

Results

Vitamin D PGSs were associated with inattention in the ADHD sample and with hyperactivity when inattention symptoms were included as covariates. In the nutrigenetic sample, CYP2R1 rs10741657 and DHCR7 rs12785878 were nominally associated with impulsivity and hyperactivity, respectively, and both with vitamin D levels. In the clinical sample, RXRG rs2134095 was associated with impulsivity.

Discussion

Our findings suggest a shared genetic architecture between vitamin D levels and ADHD symptoms, as evidenced by the associations observed with PGS and specific genes related to vitamin D levels. Interestingly, differential effects for vitamin D PGS were found in inattention and hyperactivity, which should be considered in further studies involving ADHD.

KEYWORDS:

• ADHD
• Vitamin D
• Polygenic scores
• CYP2R1
• DHCR7
• RXRG

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Disclosure statement

The author(s) declare the following potential conflict of interest with respect to the research, authorship and/or publication of the present article: Dr. EHG was on the speaker's bureau for Novartis and Shire for the last 3 years. He also received travel awards (air tickets and hotel accommodations) for participating in two psychiatric meetings from Shire and Novartis. All other authors report no financial interests or potential conflicts of interest.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação de Amparo à Pesquisa do Estado de São Paulo; Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul; Fundação Vale do Taquari de Educação e Desenvolvimento/FUVATES.

Notes on contributors

Cibele Edom Bandeira

Cibele Edom Bandeira is a postdoctoral researcher at the University of São Paulo, Brazil. Her research focuses on the genetics of ADHD.

Fernando Godoy Pereira das Neves

Fernando Godoy Pereira das Nevesis a psychiatry, with M.Sc. in Biotechnology. His research focused on vitamin D and psychiatric-related behaviors.

Diego Luiz Rovaris

Diego Luiz Rovaris is a professor at the University of São Paulo, Brazil. His main research comprises exploring the neurobiological basis underlying the relationship between educational attainment and ADHD.

Eugenio Horacio Grevet

Eugenio Horacio Grevet is a professor at the Federal University of Rio Grande do Sul, Brazil. His projects are related to clinical and demographic aspects of ADHD in adults.

Monique Dias-Soares

Monique Dias-Soares is a biomedicine undergrad student at the University of São Paulo, Brazil.

Caroline da Silva

Caroline da Silva is a biomedicine undergrad student at the University of Vale do Taquari, Brazil.

Fabiane Dresch

Fabiane Dresch is a nutritionist, with Ph.D. in Biotechnology. Her research focused on the nutrigenetic aspects of caffeine consumption.

Bruna Santos da Silva

Bruna Santos da Silva is a postdoctoral researcher at the University of São Paulo, Brazil, working on the genetics of ADHD in adults.

Claiton Henrique Dotto Bau

Claiton Henrique Dotto Bau is a senior professor at the Federal University of Rio Grande do Sul, Brazil. His projects are related to genetics and genomics of adulthood ADHD.

Flávio Milman Shansis

Flávio Milman Shansis is a senior psychiatry and a professor at the University of Vale do Taquari, Brazil. His projects are related to mood disorders.

Júlia Pasqualini Genro

Júlia Pasqualini Genro is a professor at the Federal University of Health Sciences of Porto Alegre, Brazil. Her research is related to the genetics of ADHD in children.

Verônica Contini

Verônica Contini is a professor at the University of Vale do Taquari, Brazil. Her research is primarily focused on exploring the interplay between nutrition, genetics, and psychiatric-related behaviors.