我们对有可能患躁郁症的后代了解多少?

IF 6.1 2区 医学 Q1 CLINICAL NEUROLOGY European Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1016/j.euroneuro.2024.08.020
John Nurnberger , Melvin McInnis , Janice Fullerton , Philip Mitchell , Howard Edenberg , Leslie Hulvershorn , Emma Stapp , Holly Wilcox , Neera Ghaziuddin , Masoud Kamali , Gloria Roberts
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引用次数: 0

摘要

高风险模式本质上是一种遗传流行病学研究,类似于双胞胎研究、领养研究和家庭研究。提出的问题是疾病在发病前是什么样的? 是什么决定了风险状态与发病之间的转变?这些问题与风险基因型的发育表现以及风险与恢复力之间的相互作用有关。我们一直在跟踪的特定样本包括 307 名处于风险中的年轻人(躁狂症患者的直系亲属)和 166 名对照组,这些样本在过去 15 年中一直在跟踪。美国的确定地点包括印第安纳大学医学院、约翰霍普金斯大学、密歇根大学和圣路易斯华盛顿大学。我们还与澳大利亚悉尼的新南威尔士大学进行了合作。所有研究地点都采用了类似的评估方法(KSADS-BP 和 DIGS)以及一系列自我评估工具。所有参与者都提供了 DNA 血液。所有参与者都完成了基因组学分析并计算了多基因风险评分,103 人获得了 DNA 甲基化数据。诊断结果与多基因风险有关(Fullerton 等人,2015 年,PMID 26178159;Zwicker 等人,2023 年,PMID 36856707;Freeman 等人,未发表)。多基因风险与创伤史相互作用,增加了高风险后代企图自杀的几率(Wilcox 等人,2017 PMID 29173741)。多基因风险还与感知到的家庭互动模式有显著的相互作用(Stapp et al, 2023 PMID 37378048)。不同的合并症模式预示着高风险后代的主要情绪障碍,包括儿童期和青春期早期的内化障碍和外化障碍。这些合并症模式与不同的多基因特征有关(Fullerton 等人,未发表)。在文献中,专门针对 BD 出现的研究表明,阈下躁狂/狂躁症状是发病前的指标(Hafeman 等人,2017 PMID 28678992)。对高危后代早期症状指标的研究也牵涉到睡眠障碍(Duffy et al, 2019 PMID 30525908),这可能与病前昼夜节律紊乱有关。虽然BD在临床上表现为一种独特的综合征,但该疾病的遗传易感性和发育过程却很复杂。虽然 BD 在临床上表现为一种独特的综合征,但其遗传倾向和发育过程是复杂的。BD 风险在表型上可能表现为内化障碍、外化障碍或昼夜节律紊乱。成人躁狂症可能是单相躁狂症,也可能是双相躁狂症,病程和治疗反应受发病前和合并症的影响。米切尔博士和富勒顿博士对其中的一些大脑机制进行了描述。
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WHAT DO WE KNOW ABOUT OFFSPRING AT RISK FOR BIPOLAR DISORDER AND WHAT REMAINS TO BE DISCOVERED
The High Risk paradigm is inherently a genetic epidemiologic study, similar to twin studies, adoption studies, and family studies. The questions posed are: What does the disorder look like before its onset? and What determines the transition between the risk state and onset of illness? These questions relate to the developmental expression of the risk genotype and interactions between risk and resilience.
Many studies have been done using this paradigm in bipolar disorder (BD). The particular sample we have been following comprises 307 young people at risk (first-degree relative of a proband with BD) and 166 controls, followed over the past 15 years. Ascertainment sites in the US are Indiana University School of Medicine, Johns Hopkins University, the University of Michigan and Washington University in St. Louis. We have collaborated with the University of New South Wales in Sydney, Australia. Similar methods of assessment (KSADS-BP and DIGS) have been used in all sites, along with a battery of self-assessment instruments. All participants have provided blood for DNA. All have had GWAS completed and polygenic risk scores calculated and 103 have DNA methylation data. A series of follow-up assessments were carried out over 2007-2020.
Diagnostic outcome is related to polygenic risk (Fullerton et al, 2015 PMID 26178159; Zwicker et al, 2023 PMID 36856707, Freeman et al, unpublished). Polygenic risk interacts with history of trauma to increase the chances of attempted suicide in high-risk offspring (Wilcox et al, 2017 PMID 29173741). Polygenic risk also interacts dramatically with perceived pattern of family interaction (Stapp et al, 2023 PMID 37378048).
Different patterns of comorbidity predicted major mood disorder in high-risk offspring, including both internalizing and externalizing disorders during childhood and early adolescence. These patterns of comorbidity are related to distinct polygenic signatures (Fullerton et al, unpublished).
In the literature, studies focused specifically on the emergence of BD have implicated subthreshold hypomanic/manic symptomatology as a premorbid indicator of developing illness (Hafeman et al, 2017 PMID 28678992). Study of early symptomatic indicators in high-risk offspring have also implicated sleep disorders (Duffy et al, 2019 PMID 30525908) and this may relate to premorbid disruption of circadian rhythms.
Although BD presents clinically as a distinctive syndrome, the genetic predisposition and developmental course of the disorder is complex. Risk for BD may be expressed phenotypically as an internalizing disorder, an externalizing disorder, or a disruption of circadian rhythms. The adult form of the disorder may be unipolar or bipolar, and course and treatment response are influenced by premorbid and comorbid conditions. Brain mechanisms involved are emerging and some of these are described by Drs. Mitchell and Fullerton.
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来源期刊
European Neuropsychopharmacology
European Neuropsychopharmacology 医学-精神病学
CiteScore
10.30
自引率
5.40%
发文量
730
审稿时长
41 days
期刊介绍: European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.
期刊最新文献
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