Abstract
Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual–motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.
Highlights
Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 8 to 18% of the population [1,2,3,4]
Genetic studies in ADHD have mainly focused on identifying associations with nuclear symptoms [76], with genes delineating visual–constructional skills at the perceptual organization level being identified in Caucasian and Asian populations [77]
We explore the association between Single nucleotide polymorphisms (SNPs) and endophenotypes of working memory and perceptual organization [49] in 113 nuclear families from an understudied Caribbean community segregating ADHD and inhabiting the metropolitan area of Barranquilla, Colombia
Summary
Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 8 to 18% of the population [1,2,3,4]. ADHD-affected individuals show a myriad of symptoms in different dimensions, and evident difficulties in sensory modalities and perceptual organization [28], working memory [29] and attention use in tasks based on visuospatial aspects [30,31,32,33], which are important constructs for spatial and verbal processing in higher order tasks [34] and are crucial for the identification and recognition of objects and surfaces in the environment [35] Such difficulties coexist with cognitive and behavioral aspects [36]. Our overarching hypothesis is that genetic variation implicated in conferring susceptibility to ADHD is associated with working memory and perceptual organization, which in turn may help to better understand the underlying mechanisms shaping the complexity of multisensorial alterations in ADHD
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