Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, Los Angeles (Ching, Villalon Reina, Zavaliangos-Petropulu, Thompson); Department of Biomedical Engineering, Armour College of Engineering, Illinois Institute of Technology, Chicago (Gutman); Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles (Ching, Sun, Lin, Jonas, Pacheco-Hansen, Vajdi, Forsyth, Bearden); Department of Psychology, UCLA, Los Angeles (Ching, Forsyth, Bearden); Department of Biomedical Engineering, Oregon Health and Science University, Portland (Ragothaman); Department of Biomedical Engineering, Duke University, Durham, N.C. (Isaev); Graduate Interdepartmental Program in Neuroscience, UCLA School of Medicine, Los Angeles (Lin, Jonas); Department of Psychiatry, University of Pittsburgh, Pittsburgh (Jalbrzikowski); Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands (Bakker, van Amelsvoort); Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Bakker); Department of Psychology, Syracuse University, Syracuse, N.Y. (Antshel); Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse (Fremont, Kates); School of Psychology, University of Newcastle, Newcastle, Australia (Campbell, McCabe); MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis (McCabe, Durdle, Goodrich-Hunsaker, Simon); Institute of Psychiatry, Psychology, and Neuroscience, Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, King's College London (Craig, Daly, Gudbrandsen, C.M. Murphy, D.G. Murphy); Bethlem Royal Hospital, National Institute for Health Research Maudsley Biomedical Research Centre, and SLaM NHS Foundation Trust, National Autism Unit, London (Craig); Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London (C.M. Murphy, D.G. Murphy); Department of Psychiatry, Royal College of Surgeons in Ireland, and Education and Research Centre, Beaumont Hospital, Dublin (K.C. Murphy); Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands (Fiksinski, Koops, Vorstman); Clinical Genetics Research Program (Bassett, Fiksinski, Chow), Clinical Genetics Service (Chow), Campbell Family Mental Health Research Institute (Bassett), Centre for Addiction and Mental Health, Toronto; Dalglish Family 22q Clinic (Bassett, Fiksinski), Department of Mental Health, and Toronto General Hospital Research Institute (Bassett); University Health Network, Toronto (Fiksinski, Bassett); Department of Psychiatry, University of Toronto, Toronto (Bassett, Vorstman, Chow); Program in Genetics and Genome Biology, Research Institute, and Department of Psychiatry, Hospital for Sick Children, Toronto (Vorstman); Division of Human Genetics and 22q and You Center, Children's Hospital of Philadelphia, Philadelphia (Crowley, Emanuel, McDonald-McGinn, Zackai); Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia (Emanuel, McDonald-McGinn, Zackai); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia (Gur); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia (Roalf, Ruparel); Departments of Radiology and Psychiatry, Hospital of the University of Pennsylvania, Philadelphia (Schmitt); Department of Psychological and Brain Sciences, University of California, Santa Barbara (Durdle); Department of Neurology, University of Utah, Salt Lake City (Goodrich-Hunsaker); Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto (Butcher); Department Psychiatry, University of British Columbia, Vancouver (Vila-Rodriguez); MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Cunningham, Doherty, Linden, Moss, Owen, van den Bree); Cardiff University Brain Research Imaging Centre, Cardiff, U.K. (Doherty, Linden); Department of Psychiatry, Pontificia Universidad Católica de Chile, Santiago (Crossley); Clinica Alemana, Universidad del Desarrollo, Centro de Genética y Genomica, Facultad de Medicina, Santiago (Repetto); Departments of Neurology, Psychiatry, Radiology, Engineering, Pediatrics, and Ophthalmology, University of Southern California, Los Angeles (Thompson).
Am J Psychiatry. 2020 Jul 1;177(7):589-600. doi: 10.1176/appi.ajp.2019.19060583. Epub 2020 Feb 12.
OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.
目的：22q11.2 缺失综合征（22q11DS）是精神分裂症最强的已知遗传风险因素之一。之前的研究报告称，22q11DS 存在皮质下脑结构的变化。为了更好地描述 22q11DS 的皮质下改变，包括临床和遗传异质性的调节作用，作者研究了来自 ENIGMA 22q11.2 缺失综合征工作组的大型多中心神经影像学队列。
方法：使用针对总体积和皮质下形状形态计量学的协调方案，对 533 名 22q11DS 患者和 330 名匹配的健康对照者（年龄范围 6-56 岁；49%为女性）进行了皮质下结构的测量。
结果：与对照组相比，22q11DS 组的颅内体积（ICV）和丘脑、壳核、海马和杏仁核体积较小，而侧脑室、尾状核和伏隔核体积较大（Cohen's d 值为-0.90 至 0.93）。形态分析显示，22q11DS 组所有结构均存在复杂差异。较大的 A-D 缺失与较小的 A-B 缺失相比，与更广泛的形态改变相关。伴有精神病的 22q11DS 患者的 ICV 以及海马、杏仁核和丘脑体积较小（Cohen's d 值为-0.91 至 0.53），而不伴有精神病的 22q11DS 患者则较大。形态分析显示，这些结构的子区域的厚度和表面积较低。与 ENIGMA 联盟研究的其他神经精神障碍的皮质下发现相比，伴有精神病的 22q11DS 患者与精神分裂症、双相情感障碍、重度抑郁症和强迫症患者之间存在显著的趋同。
结论：在迄今为止最大的 22q11DS 神经影像学研究中，作者发现皮质下脑结构广泛改变，这些改变受缺失大小和精神病的影响。研究结果表明，22q11DS 相关精神病、特发性精神分裂症和其他严重神经精神疾病之间存在显著重叠。
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