Psychopathology in adults with copy number variants.
Psychopathology in adults with copy number variants.
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DOI：
10.1017/s0033291721005201
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发表时间：
2023-05
影响因子：
6.9
通讯作者：
Linden, Stefanie C.
中科院分区：
文献类型：
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作者：
Adams, Rachael L.;Baird, Alister;Smith, Jacqueline;Williams, Nigel;van den Bree, Marianne B. M.;Linden, David E. J.;Owen, Michael J.;Hall, Jeremy;Linden, Stefanie C.
关键词：
拷贝数变异(CNV)与精神分裂症、自闭症和智力残疾的风险有关。然而，人们对他们成年后的精神病理谱知之甚少。我们调查了成年CNV携带者的精神表型，并比较了通过临床遗传学服务确定的先证者和不是携带者的先证者。124名成年参与者(年龄18-76岁)，每人携带15个罕见的CNV之一，通过各种来源招募，包括临床遗传学服务、基因变异携带者慈善机构和在线广告。一系列精神病学评估被用来确定精神病理学。与普通人群相比，CNV组的精神病理频率一直较高。我们发现，神经发育障碍(NDDS)(48%)、情绪障碍(42%)、焦虑障碍(47%)和人格障碍(73%)的发病率特别高，精神疾病多发病的比例也很高(诊断中位数：非先证者2例，先证者3例)。先证者(N=45；NDD：39[87%]；精神病：8[18%])和精神障碍(OR=6.8，95%CI 1.3~36.3；p=0.025)的发生率显著高于非先证者(N=79；NDD：20[25%]；精神病：3[4%])。参与者也有与所有器官系统有关的躯体诊断，特别是圆锥干心脏畸形(特别是22q11.2缺失综合征患者)、肌肉骨骼疾病、免疫学和内分泌疾病。成年CNV携带者焦虑和人格障碍的发生率明显增加，以前没有报道过，精神多发病的发生率也很高。我们的发现支持对CNV携带者进行深入的精神病学和医学评估，并建立多学科的临床服务。
Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood. We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18–76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology. The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32–16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3–36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases. Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.