Childhood Onset Schizophrenia

儿童期发病的精神分裂症

• 批准号: 6671567
• 负责人: JUDITH L. RAPOPORT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6671567
• 关键词: adolescence (12-20); brain imaging /visualization /scanning; child (0-11); chromosome deletion; chromosome translocation; clinical research; clozapine; developmental psychology; diagnosis quality /standard; disease /disorder onset; family genetics; haloperidol; human subject; human therapy evaluation; interview; magnetic resonance imaging; mass screening; medical records; mental disorder chemotherapy; mental disorder diagnosis; neurobiology; psychopharmacology; visual tracking

Children and adolescents meeting DSM-IV criteria for schizophrenia are being obtained through vigorous national recruiting. Seventy-five subjects and their families have participated to date in this study of the phenomenology, neurobiology and pharmacologic response of childhood onset schizophrenia. Over 1200 medical records have been reviewed from which 250 patients and their families appearing to meet DSM-IV criteria for schizophrenia with onset of psychosis prior to age 12, were screened in person. A total of 85 received the diagnosis of schizophrenia at screening. A large number of children are receiving the diagnosis of schizophrenia inappropriately resulting in inappropriate treatment, even at major academic centers. Our findings to date indicate continuity between childhood onset and later onset schizophrenia, with evidence that childhood onset schizophrenia may result from a more severe neurodevelopment lesion. Pilot family/genetic data indicate three cases (10%) have familial schizophrenia, not higher than seen with NIMH adult cases; one subject had a 1:7 balanced chromosomal translocation; three subjects had a microdeletion at 22q11; one had 45x0 (Turners Syndrome). Three of 45 full siblings are mentally retarded. Probands show greater premorbid developmental delay particularly for language, than seen for the later onset disorder. Autonomic and eye tracking measures parallel these of adult schizophrenia. Brain MRI abnormalities resemble those of adult onset schizophrenia with the exception of more striking and consistent progression with age. A double-blind comparison of olanzapine and clozapine is ongoing. Several lines of evidence indicate greater genetic loading for these cases and our national case finding is being expanded to obtain 120 probands for future genetic studies.

正在通过积极的全国招募来招募符合 DSM-IV 精神分裂症标准的儿童和青少年。迄今为止，已有 75 名受试者及其家人参与了这项关于儿童期发病精神分裂症的现象学、神经生物学和药理学反应的研究。我们审查了 1200 多份医疗记录，对 250 名似乎符合 12 岁之前出现精神病的精神分裂症 DSM-IV 标准的患者及其家人进行了亲自筛查。共有 85 人在筛查时被诊断为精神分裂症。许多儿童被不恰当地诊断为精神分裂症，导致接受不恰当的治疗，即使是在主要的学术中心也是如此。迄今为止，我们的研究结果表明儿童期发病和后期发病的精神分裂症之间存在连续性，有证据表明儿童期发病的精神分裂症可能是由更严重的神经发育病变引起的。飞行员家庭/遗传数据表明 3 例 (10%) 患有家族性精神分裂症，并不高于 NIMH 成人病例；一名受试者有 1:7 平衡染色体易位；三名受试者在 22q11 处有微缺失；其中一名患有 45x0（特纳综合症）。 45 个兄弟姐妹中有 3 个患有智力障碍。先证者表现出比晚发疾病更大的病前发育迟缓，尤其是语言发育迟缓。自主神经和眼球追踪测量与成人精神分裂症的测量相似。脑部 MRI 异常类似于成人发病的精神分裂症，但随着年龄的增长会出现更显着且一致的进展。奥氮平和氯氮平的双盲比较正在进行中。多项证据表明这些病例的基因负荷更大，我们的国家病例发现正在扩大，以获取 120 名先证者用于未来的基因研究。