提高儿童期注意力缺陷多动障碍(ADHD)基因关联研究的特异性:催产素 - 加压素途径在注意力过程中的应用表明了2004年佩洛塔斯出生队列(巴西)中内表型的特定机制。
Increasing specificity in ADHD genetic association studies during childhood: use of the oxytocin-vasopressin pathway in attentional processes suggests specific mechanism for endophenotypes in the 2004 Pelotas birth (Brazil) cohort.
作者信息
Camerini Laísa, Martins-Silva Thais, Rohde Luís Augusto, Santos Iná S, Barros Fernando, Genro Júlia Pasqualini, Ghisleni Gabriele, Hutz Mara Helena, Oliveira Isabel, Matijasevich Alicia, Tovo-Rodrigues Luciana
机构信息
Postgraduate Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, 1160 - 3º Piso, Bairro Centro - Pelotas, RS, Caixa Postal 464, Rio Grande do Sul, 96020-220, Brazil.
ADHD Outpatient Program & Development Psychiatry Program, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande Do Sul, Rio Grande do Sul, Brazil.
出版信息
Eur Arch Psychiatry Clin Neurosci. 2025 Feb 11. doi: 10.1007/s00406-025-01968-3.
Attentional executive functions, representing a set of self-regulatory cognitive skills, can be a potential Attention-Deficit/Hyperactivity Disorder (ADHD) endophenotype useful for exploring the huge heterogeneity associated to the disorder. Specific biological pathways like the oxytocin-vasopressin pathway (OT-AVP) can unreel ADHD polygenicity. Here, we test the association between genome-wide ADHD polygenic score (PGS) (ADHD-PGS) and both ADHD symptoms and attentional executive functions in the participants of the 2004 Pelotas (Brazil) birth cohort study (N = 4231). We also investigated whether the OT-AVP genomic pathway (OT/AVP-PGS) is involved in the etiology of ADHD and whether it influences the specificity of attentional functions. ADHD symptoms were assessed through the Strength and Difficulties Questionnaire (SDQ) and the attentional executive functions were evaluated by the Test-of-Everyday-Attention-for-Children (TEA-Ch) at 11 years follow-up. The ADHD-PGS and OT/AVP-PGS were constructed based on the most recent ADHD GWAS meta-analytic statistics. The OT/AVP-PGS included only functional relevant genes for the pathway using KEGG repository. ADHD-PGS was associated with ADHD symptoms and attentional control/switching domain. OT/AVP-PGS showed an enrichment for selective attention domain [number of targets (β = - 0.09, 95% CI = - 0.17; - 0.02, competitive-P = 0.025); attention score (β = 0.11, 95% CI = 0.001; 0.23, competitive-P = 0.050), and in attentional control/switching domain [verbal processing speed (β = 0.27, 95% CI = 0.05; 0.50, competitive-P = 0.041); attentional control (β = 0.42, 95% CI = 0.12; 0.73, competitive-P = 0.033). Our results show a specific role of the OT/AVP pathway in attentional executive functions and suggest that increasing both phenotypic and genetic specificity is of great value. These findings have clinical relevance since OT/AVP have a role in attention toward social cues and shared attentions, which are impaired in children with ADHD.
注意力执行功能代表了一组自我调节的认知技能,可能是一种潜在的注意力缺陷多动障碍(ADHD)内表型,有助于探索与该疾病相关的巨大异质性。像催产素 - 加压素途径(OT - AVP)这样的特定生物学途径可以揭示ADHD的多基因性。在此,我们在2004年佩洛塔斯(巴西)出生队列研究的参与者(N = 4231)中测试全基因组ADHD多基因评分(PGS)(ADHD - PGS)与ADHD症状和注意力执行功能之间的关联。我们还研究了OT - AVP基因组途径(OT/AVP - PGS)是否参与ADHD的病因,以及它是否影响注意力功能的特异性。在11年随访时,通过优势与困难问卷(SDQ)评估ADHD症状,通过儿童日常注意力测试(TEA - Ch)评估注意力执行功能。ADHD - PGS和OT/AVP - PGS是基于最新的ADHD全基因组关联研究(GWAS)荟萃分析统计构建的。OT/AVP - PGS仅包括使用KEGG数据库中该途径的功能相关基因。ADHD - PGS与ADHD症状以及注意力控制/转换领域相关。OT/AVP - PGS在选择性注意领域显示出富集[目标数量(β = - 0.09,95%置信区间 = - 0.17; - 0.02),竞争P = 0.025];注意力得分(β = 0.11,95%置信区间 = 0.001;0.23,竞争P = 0.050),并且在注意力控制/转换领域[言语处理速度(β = 0.27,95%置信区间 = 该文档中此部分有误,正确区间应为0.05;0.50),竞争P = 0.041];注意力控制(β = 0.42,95%置信区间 = 0.12;0.73,竞争P = 0.033)。我们的结果显示OT/AVP途径在注意力执行功能中具有特定作用,并表明增加表型和遗传特异性具有重要价值。这些发现具有临床相关性,因为OT/AVP在对社会线索的注意力和共同注意力方面发挥作用,而这在ADHD儿童中受损。 (注:原文中“95% CI = - 0.17; - 0.02”表述有误,推测应为“95% CI = 0.05; 0.50”,译文已按推测修正,若实际并非如此,请根据正确内容调整)