SLC6A1 gene involvement in susceptibility to attention-deficit/hyperactivity disorder: A case-control study and gene-environment interaction

Yuan, Fang-fen; Gu, Xue; Huang, Xin; Zhong, Yan; Wu, Jing

doi:10.1016/j.pnpbp.2017.04.015

Cited by 20 publications

(15 citation statements)

References 59 publications

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“…13 Recently, a study found that selected SLC6A1 variants may correlate with a higher risk of Attention-deficit/hyperactivity disorder (ADHD) in humans. 14 …”

Section: | Discussionmentioning

confidence: 99%

“…13 Recently, a study found that selected SLC6A1 variants may correlate with a higher risk of Attention-deficit/hyperactivity disorder (ADHD) in humans. 14 Of interest, 3/34 SLC6A1 variant carriers never had epileptic seizures, but manifested only learnings disabilities or mild ID with or without autistic features, which represent a previously undescribed phenotype associated with SLC6A1. Two of these individuals had relatives, carrying the same variant, with an MAE phenotype, suggesting variable expressivity possibly due to either genetic or environmental modifying factors, and indicating that genotype-phenotype correlations are not straightforward.…”

Section: Cognitive and Behavioral Deficitsmentioning

confidence: 99%

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Defining the phenotypic spectrum of SLC6A1 mutations

et al. 2018

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“…13 Recently, a study found that selected SLC6A1 variants may correlate with a higher risk of Attention-deficit/hyperactivity disorder (ADHD) in humans. 14 …”

Section: | Discussionmentioning

confidence: 99%

Section: Cognitive and Behavioral Deficitsmentioning

confidence: 99%

Defining the phenotypic spectrum of SLC6A1 mutations

et al. 2018

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“…Considering the role of GABA concentrations in sharpening the signal-to-noise ratio, it is not surprising that depletion of GABA transporters can cause hyperactivity and inattention phenotypes in the animal model of ADHD (Chen et al ., 2015). Consistently, several single-nucleotide polymorphisms (SNPS) in GABA transporter 1 ( GAT1) gene are associated with symptoms in people with ADHD (Yuan et al ., 2017). Thus, alterations in GABA and Glx clearance during tasks may be related to reduced GABA and Glx concentrations in subjects with ADHD.…”

Section: Discussionmentioning

confidence: 97%

Task-related excitatory/inhibitory ratios in the fronto-striatal circuitry predict attention control deficits in attention-deficit/hyperactivity disorder

Mamiya

Richards

Edden

et al. 2021

Preprint

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Reduced GABA concentrations at rest in the fronto-striatal circuitry are repeatedly implicated in cognitive symptoms of ADHD. However, recent evidence has suggested that GABA and its precursor, glutamate, are capable of undergoing dynamic modifications in response to environments. Yet, it remains unclear how the dynamics between glutamate and GABA may change when people are exerting their control of attention, and whether they would predict attention control deficits in ADHD. To study this question, we used MR spectroscopy to quantify GABA and glutamate+glutamine (Glx) concentrations in the anterior cingulate cortex (ACC) and the caudate nucleus in the fronto-striatal circuitry while subjects were performing attention control tasks. We studied 19 adults with ADHD (31-51 years) and 16 adults without ADHD (28-54). We found GABA and Glx concentrations during the tasks increased in both subjects with or without ADHD, but the extent of increases was significantly reduced in subjects with ADHD. Notably, E/I ratios (Glx/GABA) also increased and significantly predicted error rates while subjects with or without ADHD performed the Stroop and Flanker tasks. Critically, regression models including E/I ratios, GABA concentrations, and the ADHD diagnosis significantly predicted task performance in these tasks. Furthermore, clear interactions among these factors predicted the impaired attention control in the Flanker task in subjects with ADHD. These findings demonstrate for the first time that E/I ratios in the ACC and the caudate nucleus increased when people exerted their control of attention, and suggest that reduced GABA contribution to E/I ratio in these two brain regions may account for cognitive deficits in ADHD.

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“…The etiopathogenesis of ADHD is not clear; however, both genetic ( Yuan et al, 2017 ) and environmental factors (pre-, peri-, and postnatal environmental factors) are believed to be involved ( Mick et al, 2002 ; Howe, 2010 ; Silva et al, 2014 ). In some studies, the interaction between genetic and environmental factors was also found to increase the risk of ADHD ( Howe, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Attention Deficit/Hyperactivity Disorder With Events Occurring During Pregnancy and Perinatal Period

Shen

Zhou

et al. 2021

Front. Psychol.

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Background: The relationship of events occurring during pregnancy and perinatal period with attention deficit/hyperactivity disorder (ADHD) is not clear. Thus, the focus of the current study was to examine the effects of events occurring during pregnancy and perinatal period on ADHD.Methods: A two-phase cross-sectional study was performed across 13 schools in Changsha and Yiyang cities from March to December, 2014. We preliminarily screened all students using CBCL and established the diagnosis using Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). A total of 3,418 questionnaires were effectively completed in this study.Results: History of threatened abortion (TA) [odds ratio (OR): 1.707 (1.201–2.426)] (vs. No-TA) and neonatal asphyxia (NA) [OR: 2.497(1.225–5.09)] (vs. health) showed a positive association with ADHD. On subgroup analysis, TA [OR: 2.216 (1.458–3.369)] (vs. No-TA) was a risk factor for ADHD without comorbidity; instrumental delivery [OR: 2.748 (1.057–7.142)] (vs. natural birth) and NA [OR: 2.789 (1.222–6.361)] (vs. health) were risk factors for ADHD in the subgroup of ADHD with comorbidity; TA (vs. no-TA) and NA (vs. health) were risk factors for ADHD among male students [ORs: 2.232 (1.439–3.462) and 2.808 (1.115–7.068), respectively], while low birth weight (LBW) (vs. normal birth weight) was a risk factor [OR: 2.054 (1.063–3.967)] for ADHD among female students.Conclusion: TA was a risk factor for ADHD in the absence of comorbid conditions; instrumental delivery and NA were risk factors for ADHD in the subgroup of ADHD with comorbidity; TA and NA were risk factors for ADHD among male students. LBW was a risk factor for ADHD among female students.

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SLC6A1 gene involvement in susceptibility to attention-deficit/hyperactivity disorder: A case-control study and gene-environment interaction

Cited by 20 publications

References 59 publications

Defining the phenotypic spectrum of SLC6A1 mutations

Defining the phenotypic spectrum of SLC6A1 mutations

Task-related excitatory/inhibitory ratios in the fronto-striatal circuitry predict attention control deficits in attention-deficit/hyperactivity disorder

Association of Attention Deficit/Hyperactivity Disorder With Events Occurring During Pregnancy and Perinatal Period

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