ADHD Endophenotypes in Caribbean Families

Cervantes-Henríquez, Martha L; Acosta-López, Johan E.; Martínez-Banfi, Martha; Vélez, Jorge I.; Mejía-Segura, Elsy; Lozano-Gutiérrez, S. G.; Sánchez-Rojas, Manuel; Zurbarán, Mayra; Zurek, Eduardo; Arcos‐Burgos, Mauricio; Piñeda, David; Puentes-Rozo, Pedro J.

doi:10.1177/1087054718763741

Cited by 9 publications

(23 citation statements)

References 74 publications

(106 reference statements)

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“…The Grupo de Neurociencias del Caribe carried out an extensive clinical, neurological, and neuropsychological evaluation to define ADHD status and the presence of other comorbidities, using a multi-stage scheme. The full evaluation protocol is described elsewhere [30]. Briefly, we employed the Diagnostic Interview for Children and Adolescents version IV (DICA-IV) [31,32] as the gold standard to assess the diagnosis of ADHD and/or ADHD-related comorbidities including CD and ODD in children, adolescents, and adults.…”

Section: Methodsmentioning

confidence: 99%

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Puentes-Rozo

Acosta-López

Cervantes-Henríquez

et al. 2019

Cells

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Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

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Section: Methodsmentioning

confidence: 99%

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Puentes-Rozo

Acosta-López

Cervantes-Henríquez

et al. 2019

Cells

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“…[47] These SNPs were also found to be associated with enhanced susceptibility of patients infected with CHIKV to developing fever, joint pain, and rashes. [47] As our study population has a strong African admixture, [48][49][50] [51] future studies should focus on determining the contribution of these SNPs in this understudied population. Furthermore, considering that CHIKV originated in the African continent, genetic ancestry in our population could help to elucidate its influence on host response.…”

Section: Discussionmentioning

confidence: 99%

Chikungunya outbreak (2015) in the Colombian Caribbean: Latent classes and gender differences in virus infection

et al. 2020

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Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the Togaviridae family, is part of a group of emergent diseases, including arbovirus, constituting an increasing public health problem in tropical areas worldwide. CHIKV causes a severe and debilitating disease with high morbidity. The first Colombian autochthonous case was reported in the Colombian Caribbean region in September 2014. Within the next two to three months, the CHIKV outbreak reached its peak. Although the CHIKV pattern of clinical symptomatology has been documented in different epidemiological studies, understanding of the relationship between clinical symptomatology and variation in phenotypic response to CHIKV infection in humans remains limited. We performed a cross sectional study following 1160 individuals clinically diagnosed with CHIKV at the peak of the Chikungunya outbreak in the Colombian Caribbean region. We examined the relationship between symptomatology and diverse phenotypic responses. Latent Class Cluster Analysis (LCCA) models were used to characterize patients' symptomatology and further identify subgroups of individuals with differential phenotypic response. We found that most individuals presented fever (94.4%), headache (73.28%) and general discomfort (59.4%), which are distinct clinical symptoms of a viral infection. Furthermore, 11/26 (43.2%) of the categorized symptoms were more frequent in women than in men. LCCA disclosed seven distinctive phenotypic response profiles in this population of CHIKV infected individuals. Interestingly, 282 (24.3%) individuals exhibited a lower symptomatic "extreme" phenotype and 74 (6.4%) patients were within the severe complex "extreme" phenotype. Although clinical symptomatology may be diverse, there are distinct symptoms or group of symptoms that can be correlated with differential phenotypic response and perhaps susceptibility to CHIKV infection, especially in the female population. This suggests that, comparatively to men, women are a CHIKV at-risk population. Further study is needed to validate these results and determine whether the distinct LCCA profiles are a result of the immune response or a mixture of genetic, lifestyle and environmental factors. Our findings could contribute to the development of machine learning approaches to PLOS NEGLECTED TROPICAL DISEASES

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“…No children or adults were treated with medication for ADHD at initial assessment. The full neurological, neuropsychological and psychological assessment, as well as demographic information, has been reported elsewhere [49,52,53]. Briefly, 408 individuals belonging to 120 nuclear families and ascertained from probands affected by ADHD initially participated in our clinical and genetic studies of ADHD.…”

Section: Subjectsmentioning

confidence: 99%

“…ADHD diagnosis was assessed in all individuals using behavioral [54][55][56] and psychopathological interviews, which include the structured Diagnostic Interview for Children and Adults (DICA) version IV [57]. This interview (1) considers the A criterion of the DSM-IV, (2) utilizes a systematic approach to collect clinical information about ADHD symptoms exhibited by an individual using a binary classification (0 = absent; 1 = present) system, and (3) has been extensively used by our group and others in genetic studies of ADHD [27,49,52,53,[58][59][60]. ADHD symptom data were collected during the clinical assessment stage, where 11 schools were visited (seven of medium socio-economic stratum).…”

Section: Subjectsmentioning

confidence: 99%

“…We recently identified ADHD cognitive endophenotypes related to working memory and perceptual organization in nuclear families segregating ADHD [49] in a Caribbean community with one of the largest African admixtures in Colombia and South America [50][51][52]. Now, in this study, we explore whether genetic variation is a major component underpinning the biological basis of these traits.…”

Section: Introductionmentioning

confidence: 99%

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ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD

et al. 2021

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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.

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ADHD Endophenotypes in Caribbean Families

Abstract: We have dissected new cognitive endophenotypes in ADHD that can be suitable to assess the neurobiological and genetic basis of ADHD.

Cited by 9 publications

References 74 publications

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Chikungunya outbreak (2015) in the Colombian Caribbean: Latent classes and gender differences in virus infection

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD

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