Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder

Sánchez-Mora, Cristina; Richarte, Vanesa; Garcia-Martínez, Iris; Pagerols, Mireia; Corrales, Montse; Bosch, Rosa; Vidal, Raquel; Viladevall, Laia; Casas, Miguel; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Ribasés, Marta

doi:10.1002/ajmg.b.32340

Cited by 21 publications

(14 citation statements)

References 106 publications

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“…The 7R polymorphism has been proposed as one of the genetic risk factors for ADHD (22). In line with the current findings, Sánchez-Mora et al (54) had already demonstrated that the effect of the number of stressful life events on inattention scores was stronger among 7R-non-carriers than 7R-carriers. Note however, that ratings by others are needed to exclude the possibility that 7R-carriers and 7R-non-carriers report their inattention differently.…”

Section: Discussionsupporting

confidence: 90%

The Role of Gene Encoding Variation ofDRD4in the Relationship between Inattention and Seasonal Daylight

Vollebregt

Franke

Buitelaar

et al. 2019

Preprint

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Daylight is the strongest synchronizer of human circadian rhythms. The circadian pathway hypothesis posits that synchrony between daylight and the circadian system relates to (in)attention. The dopamine neurotransmitter system is implicated in regulating the circadian system as well as in (attention)-deficit hyperactivity disorder [ADHD]. We studied the role of functional genetic variation in the gene encoding of dopamine-receptor-D4 (DRD4) in the relationship between inattention and seasonal daylight (changes). Gene-by-environment (GxE) mega-analyses were performed across eight studies including 3757 adult participants (with and without ADHD). We tested 1) the Spring-focus hypothesis, in which attention in 7R-carriers normalizes with increasing daylight levels preceding measurement, 2) the Summer-born ADHD hypothesis, in which 7R-carriers report more inattention when born in spring/summer than in autumn/winter, 3) the Winter-born ADHD hypothesis, opposing the second hypothesis. The Spring-focus hypothesis was upheld (1386 ADHD, 760 controls; d=-0.16 between periods); 7R-carriers reported even less inattention than 7R-non-carriers after winter solstice (d=0.27 between genotype-groups). Results were diagnosis-independent. Sensitivity analyses at individual study level confirmed the circannual patterns for 7Rcarriers. Incorporating geographic changes into the independent measure, we also calculated changes in sunlight levels. This approach likewise showed that inattention correlated negatively with increasing light levels in 7R-carriers (r=-.135). Results emphasize peripheral effects of dopamine and the effects of (seasonal) daylight changes on cognition.

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Section: Discussionsupporting

confidence: 90%

The Role of Gene Encoding Variation ofDRD4in the Relationship between Inattention and Seasonal Daylight

Vollebregt

Franke

Buitelaar

et al. 2019

Preprint

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“…Family-based designs are robust against population admixture and stratification, and allow conducting complex segregation analysis and linkage and association studies that would be next to impossible in case/control-based designs [32,61,62,63]. With few exceptions [64,65,66,67], recent genetic studies on ADHD have primarily focused on case/control-based designs to study genetic contributions to ADHD susceptibility [15,16,18,68,69,70].…”

Section: Discussionmentioning

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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“…A review of the last 4.5 years of the literature included 34 studies that focused on ADHD diagnosis and related symptoms. A majority of studies focused their environmental exposure on related to psychosocial [67][68][69][70][71][72][73][74][75][76][77], stress and adversity [27,75,[77][78][79][80][81][82][83][84], and trauma-related exposures [85]. Very few focused on toxicant exposure such as blood lead levels [86, 87••, 88], phthalate metabolites [89], and organophosphate pesticide exposure [90].…”

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

Musci

Augustinavicius

Volk

2019

Curr Psychiatry Rep

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Purpose of Review-We identify the recent evidence for gene-by-environment interaction studies in relation to psychiatric disorders. We focus on the key genotypic data as well as environmental exposures and how they interact to predict psychiatric disorders and psychiatric symptomatology. We direct our focus on the psychiatric outcomes that were focused on by the Psychiatric Genetics Consortium. Recent Findings-Many of the studies focus on candidate gene approaches, with most of the studies drawing upon previous literature to decide the genes of interest. Other studies used a genome-wide approach. While some studies demonstrated positive replication of previous findings, replication is still an issue within gene-by-environment interaction studies. Summary-Gene-by-environment interaction research in psychiatry globally suggests some susceptibility to environmental exposures based on genotype; however, greater clarity is needed around the idea that genetic risk may not be disorder specific.

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Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder

Cited by 21 publications

References 106 publications

The Role of Gene Encoding Variation ofDRD4in the Relationship between Inattention and Seasonal Daylight

The Role of Gene Encoding Variation ofDRD4in the Relationship between Inattention and Seasonal Daylight

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

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