The SLC6A3 gene polymorphism is related to the development of attentional functions but not to ADHD

Katarzyna Kuc,Anita Cybulska-Klosowicz,Ewa Racicka-Pawlukiewicz,Michał B Czerwinski,Maksymilian Bielecki

doi:10.1038/s41598-020-63296-x

Abstract

Neuropharmacological and human clinical studies have suggested that the brain dopaminergic system is substantively involved in normal and pathological phenotypes of attention. Dopamine transporter gene (SLC6A3) was proposed as a candidate gene for Attention-Deficit/Hyperactivity Disorder (ADHD). We investigated the effect of the SLC6A3 variants on cognitive performance in ADHD and healthy children and teenagers. Participants completed cognitive tasks measuring attentional switching, selective and sustained attention, and effectiveness of alerting, orienting and executive attention. We estimated the effects of 40 bp variable number of tandem repeat (VNTR) polymorphism located in the 3′ untranslated region (3′ UTR) (9-repeat vs 10-repeat allele) of the SLC6A3 gene, ADHD diagnosis, age, and their interactions as predictors of cognitive performance. ADHD children demonstrated deficits in most of the examined attention processes, persistent within the examined age range (9–16 years). No significant effects were observed for the interaction of ADHD and the SLC6A3 polymorphism, but the results revealed a significant main effect of SLC6A3 genotype in the entire research sample. Subjects carrying 9R allele performed the switching task significantly worse in comparison to children with 10R/10R or 10R/11R genotype. SLC6A3 polymorphism moderated age-related improvements in orienting and attentional switching. Results suggest that SLC6A3 genotype influence these attentional/cognitive functions which deficits are not the key symptoms in ADHD.

Highlights

Attention is usually conceptualized as a set of cognitive processes responsible for filtering and selecting behaviorally relevant information
The diagnosis was conducted at the clinic by an experienced team of psychiatrists and psychologists according to the diagnostic criteria of the DSM-IV TR (4th edition, text revision; American Psychiatric Association, 2000) as previously described[39] and included: an interview with patients’ parents, Diagnostic Structured Interview for Attention-Deficit/Hyperactivity Disorder (ADHD) and Hyperkinetic Disorder according to ICD-10 and DSM-IV TR40, the Behavioral Disorders Supplement of Diagnostic Interview Kiddie-SADS-Present and Lifetime Version, as well as observation of patients’ behavior
To the best of our knowledge, this is the first study on ADHD and control cohort using such a detailed and wide assessment of the attention and regression approach to analyze in more details how the attention functioning changes with age and what is the contribution of SLC6A3 3′ untranslated region (3′ UTR) variable number of tandem repeat (VNTR) variants in these processes

Summary

Introduction

Attention is usually conceptualized as a set of cognitive processes responsible for filtering and selecting behaviorally relevant information. Top-down processes rely on goals, cognitive strategies and effortful control, aiming to prioritize some stimuli over others This distinction is clearly reflected in the Posner and Petersen (1990) model of attention, where three functionally and anatomically independent networks are proposed, each of them modulated by a different neurotransmitter[2]. In prefrontal areas norepinephrine transporter (NET), is capable of mediating the reuptake of DA, which indicates its importance in regulating prefrontal brain activity[17] Both DAT and NET are established targets of therapeutics. Studies on the genetic basis of differences in attention in healthy individuals suggested the link of SLC6A3 polymorphism to executive attention[8,26]. A recent meta-analysis demonstrated no effects of SLC6A3 on cognitive functions, including attention, in healthy adults[30]

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