2013-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657890摘要：摘要注意力不足過動症(Attention-Deficit/Hyperactivity Disorder, ADHD)是常見的(5-8%)、早發性、造成長期功能障礙、具有高度遺傳性、且具有臨床上及基因學異質性的神經精神疾患。由於其障礙會持續到成年期，雖然成人ADHD在過去十年已受到西方國家相當多的重視，然而亞洲國家尚未有任何相關的研究探討此議題。此四年創新計畫的目標為追蹤計畫主持人於5年期由國衛院補助的研究發展獎助計畫(CDG, NHRI 2005-2009)所收集在兒童期已確立ADHD診斷的青少年與健康對照組以了解其在青少年後期及成人期的預後。此研究將是世界少有且完整的成人ADHD之神經認知功能及神經影像基因學研究。研究方法研究對象包括兒童期即被診斷為ADHD的217位年輕成人(男性180位，83%)，以及173位一般發展組(男性123位，71%)。在17-24歲時(距青少年期評估約六年後)，受試者將接受精神科診斷會談(ADHD+SADS, CAADID)以確認成人期ADHD診斷與其他符合DSM-IV的精神疾患，並收集血液樣本。評估內容包括標準化自填問卷(ADHD相關症狀：ASRS、CAARS-S:S；人格特質：TPQ；DSM-IV精神病理：ASRI-4；社會功能：AAQoL、WFIRS-S、WFIRS-P；家庭互動：PBI) 以及神經心理學測驗(智力：WAIS-III ；注意力控制與執行功能：CANTAB)。我們將選取30位持續出現ADHD症狀的受試者(persistent ADHD)及無ADHD、同性別、且同慣用手的手足(n=30)，以及30位無ADHD及無其他精神疾患的一般發展組，進行擴散頻譜磁振造影(DSI)及休息狀態功能性造影(resting state fMRI)，共150次腦部照影(以80%成功率計算)。我們將針對3'VNTR基因及其他與多巴胺及腎上腺素系統相關的候選基因 (DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT)，進行個案對照的關聯研究之基因定型與單套體分析。研究目的1.描述ADHD症狀於成人早期的持續性與表現模式，並探討於精神病理、社會、及執行功能層面的成人期預後；2.驗證額葉紋狀體神經迴路(frontostriatal circuitry)之腦部結構性與功能性聯結是否可作為ADHD的腦部照影內在表現型，以及其與ADHD症狀和多巴胺神經傳導系統相關基因變異的關係；3.檢測過去已報告與多巴胺和正腎上腺素傳導系統有關的候選基因(DAT1, DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT)，與ADHD症狀嚴重度、ADHD亞型 (持續性、共病情形、功能障礙、與治療效果)、與內在表現型(執行功能與結構性和功能性腦部造影)的相關性。<br> Abstract: BACKGROUNDS: Attention deficit/hyperactivity disorder (ADHD) is a common (5-8%), early-onset, long-term impairing, clinically heterogeneous neuropsychiatric disorder with high heritability. Due to its lifelong impairments up to adulthood, adult ADHD has drawn much more attention in Western studies in the past decade; however, there is no such study in Asian countries. This 4-year project aims to investigate the outcomes of a cohort of children with ADHD and healthy controls established by the PI’s 5-year CDG (NHRI 2005-2009) and will be one of few world-class studies on the topics of neurocognitive and imaging genomics on adult ADHD.METHODS: The sample consists of a cohort of 217 young adults (180 males, 83%) who were diagnosed with ADHD at childhood and 173 healthy controls (123 males, 71%). At their ages of 17-24 (around 6 years after their assessments at adolescence), they will receive psychiatric interviews (ADHD+SADS, CAADID) to make the diagnosis of ADHD and other psychiatric disorders and blood sample collection. They will complete the following questionnaires: the ASRS and CAARS-S:S for adult ADHD symptoms, the TPQ for personality characteristics, the ASRI-4 for DSM-IV psychopathology, the AAQoL and WFIRS for social functions, and the PBI for parenting styles; and perform the WAIS-III for current IQ and Cambridge Neuropsychological Test Automated Batteries for attention control and executive functioning. Among the cohort subjects, 30 subjects with persistent ADHD and their same-sex and –handedness unaffected siblings (n = 30) and 60 age-, sex-, handedness-, and IQ-matched controls will performed Diffusion Spectrum Imaging and resting-state fMRI assessments (150 assessments due to 80% success rate). We will conduct case-control and family-based association SNP and haplotype analysis of DAT1, DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT.SPECIFIC AIMS:1.To describe the manifestation and persistence of ADHD symptoms and to investigate the psychiatric, social, and executive functioning outcomes at young adulthood among children with ADHD; 2.To validate structural and functional connectivity of frontostriatal circuitry as imaging endophenotypes of ADHD by demonstrating that structural connectivity and functional connectivity of frontostriatal circuitry are altered in patients with ADHD and their unaffected siblings, are associated with ADHD symptoms, and are associated with genes related to dopamine neurotransmitter system; and3.To confirm reported candidate genes related to dopamine and noradrenergic neurotransmitter systems in the association with ADHD severity and subtypes (persistence, comorbidity, functional impairment, and treatment effects) and endophenotypes (executive function and structural and functional brain connectivity) such as DAT1, DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT.注意力不足過動症年輕成人期內在性表現型attention deficit/hyperactivity disorderyoung adulthoodendophenotype