Cortical thickness differences in the prefrontal cortex in children and adolescents with ADHD in relation to dopamine transporter (DAT1) genotype

Fernández-Jaén, Alberto; López-Martín, Sara; Albert, Jacobo; Fernández-Mayoralas, Daniel Martı́n; Fernández-Perrone, Ana Laura; Peña, Mar Jiménez de la; Calleja‐Pérez, Beatriz; Rodríguez, Manuel Recio; López-Arribas, Sonia; Muñoz-Jareño, Nuria

doi:10.1016/j.pscychresns.2015.07.005

Cited by 39 publications

(25 citation statements)

References 80 publications

(121 reference statements)

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“…There is some evidence that cortical thickness is a better trait for capturing the heritability of the brain's morphology . In children and adolescents with ADHD, thickness of the lateral prefrontal cortex and the cingulated cortex was increased in 98 cases with the 10R‐allele . Interestingly, homozygotes for the SLC6 A3 10R allele showed increased thickness in the right cingulated gyrus, but decreased cortical thickness in the lateral prefrontal cortex.…”

Section: Molecular Genetic Studiesmentioning

confidence: 99%

Recent developments in the genetics of attention‐deficit hyperactivity disorder

Grimm

Kittel‐Schneider

Reif

2018

Psychiatry Clin Neurosci

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Attention-deficit hyperactivity disorder (ADHD) is a developmental psychiatric disorder that affects children and adults. ADHD is one of the psychiatric disorders with the strongest genetic basis according to familial, twin, and single nucleotide polymorphisms (SNP)-based epidemiological studies. In this review, we provide an update of recent insights into the genetic basis of ADHD. We discuss recent progress from genome-wide association studies (GWAS) looking at common variants as well as rare copy number variations. New analysis of gene groups, so-called functional ontologies, provide some insight into the gene networks afflicted, pointing to the role of neurodevelopmentally expressed gene networks. Bioinformatic methods, such as functional enrichment analysis and protein-protein network analysis, are used to highlight biological processes of likely relevance to the etiology of ADHD. Additionally, copy number variations seem to map on important pathways implicated in synaptic signaling and neurodevelopment. While some candidate gene associations of, for example, neurotransmitter receptors and signaling, have been replicated, they do not seem to explain significant variance in recent GWAS. We discuss insights from recent case-control SNP-GWAS that have presented the first whole-genome significant SNP in ADHD.

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Section: Molecular Genetic Studiesmentioning

confidence: 99%

Recent developments in the genetics of attention‐deficit hyperactivity disorder

Grimm

Kittel‐Schneider

Reif

2018

Psychiatry Clin Neurosci

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“…For instance, several studies have reported an increased density of DAT in children and adults diagnosed with ADHD (Cheon et al, 2003; Krause et al, 2003) and meta-analytic studies have found significant associations between the 10r allele of the DAT1 and ADHD (Yang et al, 2007; Gizer et al, 2009; although see Rommelse et al, 2008 for contradictory results). Neuroimaging studies have also shown that homozygosity for the 10r allele is associated with reduced cortical thickness in the prefrontal cortex in children and adolescents diagnosed with ADHD (Fernández-Jaén et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Influence of the SLC6A3-DAT1 Gene on Multifaceted Measures of Self-regulation in Preschool Children

et al. 2017

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Development of self-regulation, the capacity to voluntarily modulate thoughts, emotions and actions is strongly related to the maturation of the dopamine-mediated executive attention network (EAN). The attention control processes associated with the EAN greatly overlap with efficiency of the executive functions and are correlated with measures of effortful control. Regulation of dopamine levels within the EAN, particularly in the basal ganglia is carried out by the action of dopamine transporters. In humans, the SLC6A3/DAT1 gene carries out the synthesis of the DAT protein. The 10-repeat allele has been associated with an enhanced expression of the gene and has been related to ADHD symptoms. Little is known about the impact of DAT1 variations on children's capacity to self-regulate in contexts that impose particular demands of regulatory control such as the school or home. This study defines a multi-domain phenotype of self-regulation and examines whether variations of the DAT1 gene accounts for individual differences in performance in 4–5 year old children. Results show that presence of the 10r allele is related to a diminished ability to exert voluntary regulation of reactivity. These findings shed light on the neurobiological mechanisms underlying individual differences in self-regulation during childhood.

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“…Another strength of this study is the use of modern neuroimaging methods to extend the set and setting hypothesis to include in vivo individual brain structure information. However, future research should also include genomic and epigenetic predictors of individual psilocybin response since allelic variations in monoaminergic genes have been linked to brain structure and therapeutic response to pharmacological treatments [76][77][78][79][80][81]. Lastly, because we assessed these relationships with a healthy sample, future research with patient populations will need to determine if our results prove to be of clinical value.…”

Section: Discussionmentioning

confidence: 99%

Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

Lewis

Preller²,

Braden

et al. 2020

Biomedicines

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Psilocybin is the psychoactive compound of mushrooms in the psilocybe species. Psilocybin directly affects a number of serotonin receptors, with highest affinity for the serotonin 2A receptor (5HT-2Ar). Generally, the effects of psilocybin, and its active metabolite psilocin, are well established and include a range of cognitive, emotional, and perceptual perturbations. Despite the generality of these effects, there is a high degree of inter-individual variability in subjective psilocybin experiences that are not well understood. Others have shown brain morphology metrics derived from magnetic resonance imaging (MRI) can predict individual drug response. Due to high expression of serotonin 2A receptors (5HT-2Ar) in the cingulate cortex, and its prior associations with psilocybin, we investigate if cortical thickness of this structure predicts the psilocybin experience in healthy adults. We hypothesized that greater cingulate thickness would predict higher subjective ratings in sub-scales of the Five-Dimensional Altered State of Consciousness (5D-ASC) with high emotionality in healthy participants (n = 55) who received oral psilocybin (either low dose: 0.160 mg/kg or high dose: 0.215 mg/kg). After controlling for sex, age, and using false discovery rate (FDR) correction, we found the rostral anterior cingulate predicted all four emotional sub-scales, whereas the caudal and posterior cingulate did not. How classic psychedelic compounds induce such large inter-individual variability in subjective states has been a long-standing question in serotonergic research. These results extend the traditional set and setting hypothesis of the psychedelic experience to include brain structure metrics.

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Cortical thickness differences in the prefrontal cortex in children and adolescents with ADHD in relation to dopamine transporter (DAT1) genotype

Cited by 39 publications

References 80 publications

Recent developments in the genetics of attention‐deficit hyperactivity disorder

Recent developments in the genetics of attention‐deficit hyperactivity disorder

Influence of the SLC6A3-DAT1 Gene on Multifaceted Measures of Self-regulation in Preschool Children

Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

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