PDF(Pubmed)
Abstract：
A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07-7.90, p = 5.31 × 10-11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.
摘要：
涉及遗传物质的微缺失或复制的一系列罕见突变(拷贝数变异(CNV))与高神经发育和精神病风险(ND-CNV)相关。在儿童神经发育状况中经常观察到易怒，然而其病因在很大程度上是未知的。遗传变异可能起作用,但是很少有研究调查ND-CNVs年轻人的易怒表现。这项研究旨在调查与没有ND-CNV的年轻人相比，罕见ND-CNV的年轻人的易怒性是否存在差异。以及在多大程度上易怒与精神病诊断和认知能力（IQ）相关。在485名患有ND-CNV的年轻人和164名兄弟姐妹对照中评估了易怒和更广泛的精神病理学。使用儿童和青少年精神病学评估。自闭症是使用社会沟通问卷进行评估的，和智商(IQ)由韦克斯勒缩写的智力量表。患有ND-CNV的年轻人中有54％达到了易怒的阈值；显着高于对照组（OR=3.77，CI=3.07-7.90，p=5.31×10-11）。当控制其他精神病合并症的存在时，ND-CNV状态仍与易怒有关。没有证据表明易怒与智商之间存在关系。在患有ND-CNV的年轻人中，易怒是临床表现的重要方面。这项工作表明，遗传变异与ND-CNVs年轻人的易怒有关，独立于精神合并症或智商障碍。临床医生应该意识到这种增加的风险，以告知管理和干预措施。
