Genetics of attention-deficit/hyperactivity disorder: current findings and future directions

Akutagava-Martins, Gláucia Chiyoko; Salatino-Oliveira, Angélica; Kieling, Christian; Rohde, Luis Augusto; Hutz, Mara H.

doi:10.1586/ern.13.30

Cited by 54 publications

(32 citation statements)

References 89 publications

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“…Targeted genes (eg, DAT1, DRD4) from classic genetic studies and newly identified genes (eg, GRM5, GRM7) from genome-wide association studies contribute all with very small effects. 28 Studies on gene-environment interactions or epigenetic changes are much needed. [29][30][31] It is well known that maternal smoking during pregnancy is a causal risk factor for fetal growth restriction.…”

Section: Discussionmentioning

confidence: 99%

Parental Smoking During Pregnancy and ADHD in Children: The Danish National Birth Cohort

Olsen²,

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Prenatal maternal smoking has been associated with attention-deficit/hyperactivity disorder in children, but the causal nature of this association is unclear. Controlling for the association with paternal smoking has been inconsistent. WHAT THIS STUDY ADDS:Women who used nicotine replacement also had children with a higher risk of attention-deficit/ hyperactivity disorder. Mother' s smoking behavior appears more important than father' s, suggesting a possible causal effect of nicotine exposure or factors related to maternal nicotine dependence.abstract BACKGROUND: Prenatal maternal smoking has been associated with attention-deficit/hyperactivity disorder (ADHD) in children, but the causal nature of this association is still under scrutiny. We examined the association with maternal smoking and nicotine replacement use during pregnancy, using association with paternal smoking as a marker of potential genetic or social confounding. METHODS:We included 84 803 singletons who participated in the Danish National Birth Cohort. Information on parental smoking was reported by the mothers during pregnancy. Children with ADHD were identified from the Danish Psychiatric Central Register, the Danish National Patient Register, and the Register of Medicinal Product Statistics by the International Classification of Diseases, 10th Revision diagnosis or medication. We also used hyperactivity/inattention score of the parent-reported Strengths and Difficulties Questionnaire, included in the 7-year follow-up of the National Birth Cohort.RESULTS: Maternal and paternal smoking during pregnancy were associated with an elevated risk of ADHD defined by hospital diagnosis, medication, and hyperactivity/inattention score, but the association was stronger for maternal smoking than for paternal smoking. Compared with children born to nonsmoking mothers and smoking fathers, children born of smoking mothers and nonsmoking fathers had a higher risk of ADHD (adjusted hazard ratio = 1.26; 95% confidence interval, 1.03 to 1.53). We also saw a higher risk of ADHD in children of mothers who used nicotine replacement during pregnancy. Dr Zhu conceptualized and designed the study, carried out the initial analyses, and drafted the initial manuscript; Drs Olsen and Obel conceptualized and designed the study, and reviewed and revised the manuscript; Mr Liew contributed to the data analyses and reviewed and revised the manuscript; Drs Li and Niclasen contributed to the conception and study design and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted. CONCLUSIONS:www.pediatrics.org/cgi

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Section: Discussionmentioning

confidence: 99%

Parental Smoking During Pregnancy and ADHD in Children: The Danish National Birth Cohort

Olsen²,

et al. 2014

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“…Genetic studies indicate that ADHD is highly heritable but is a polygenetic disorder with thousands of genes likely implicated, all with small effect size (Elia et al, 2012;Akutagava-Martins et al, 2013). Candidate gene studies have shown a small linkage with the DArelated genes DR5 and the DA transporter DAT1, as well as the catecholamine-related genes DRD4 and catechol-O-methyltransferase and the NE-related genes DBH and ADRA2A (Caylak, 2012).…”

Section: Relevance To Human Disordersmentioning

confidence: 99%

Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders

2015

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“…Candidate gene studies focused primarily on genes involved in monoamine systems (Gizer et al 2009). Altogether, these studies have identified many variants, generally of small effect, which do not explain the great ADHD heritability (Akutagava-Martins et al 2013).…”

Section: Received 16 March 2015 Revised 28 April 2015 Accepted For mentioning

confidence: 99%

LPHN3 and attention‐deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study

Bruxel

Salatino-Oliveira

Akutagava-Martins

et al. 2015

Genes Brain and Behavior

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Latrophilin 3 (LPHN3) is a brain-specific member of the G-protein coupled receptor family associated to both attention-deficit/hyperactivity disorder (ADHD) genetic susceptibility and methylphenidate (MPH) pharmacogenetics. Interactions of LPHN3 variants with variants harbored in the 11q chromosome improve the prediction of ADHD development and medication response. The aim of this study was to evaluate the role of LPHN3 variants in childhood ADHD susceptibility and treatment response in a naturalistic clinical cohort. The association between LPHN3 and ADHD was evaluated in 523 children and adolescents with ADHD and 132 controls. In the pharmacogenetic study, 172 children with ADHD were investigated. The primary outcome measure was the parent-rated Swanson, Nolan and Pelham Scale -version IV applied at baseline, first and third months of treatment with MPH. The results reported herein suggest the CGC haplotype derived from single nucleotide polymorphisms (SNPs) rs6813183, rs1355368 and rs734644 as an ADHD risk haplotype (P = 0.02, OR = 1.46). Although non-significant after multiple testing correction, its interaction with the 11q chromosome SNP rs965560 slightly increases risk (P = 0.03, OR = 1.55). Homozygous individuals for the CGC haplotype showed faster response to MPH treatment as a significant interaction effect between CGC haplotype and treatment over time was observed (P < 0.001). Homozygous individuals for the GT haplotype derived from SNPs rs6551665 and rs1947275 showed a nominally significant interaction with treatment over time (P = 0.04). Our findings replicate previous findings reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment response in children and adolescents with ADHD.

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Genetics of attention-deficit/hyperactivity disorder: current findings and future directions

Cited by 54 publications

References 89 publications

Parental Smoking During Pregnancy and ADHD in Children: The Danish National Birth Cohort

Parental Smoking During Pregnancy and ADHD in Children: The Danish National Birth Cohort

Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders

LPHN3 and attention‐deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study

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