Zubenko G S, Zubenko W N, Spiker D G, Giles D E, Kaplan B B
Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
Am J Med Genet. 2001 Dec 8;105(8):690-9. doi: 10.1002/ajmg.1554.
Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (> or = 2 episodes), early-onset (< or = 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members.
目前正在协同努力,以确定单相重度抑郁症(MDD)及相关疾病的易感基因。这些研究聚焦于复发性早发性MDD(RE-MDD),这是该疾病中遗传性最强的一种形式。本研究的目的是描述RE-MDD家族中MDD及其他情绪障碍、共病精神障碍和过高死亡率的情况。通过18岁以上的先证者共识别出81个家族,这些先证者符合复发性(≥2次发作)、早发性(≤25岁)、非精神病性、单相MDD(RE-MDD)的标准,包括407名一级亲属和835名远亲。先证者及其提供血液样本的家庭成员的精神科诊断是根据结构化个人访谈、结构化家族史评估和现有医疗记录得出的。其余参与的家庭成员和已故成员则通过家族史方法并结合现有医疗记录进行评估。根据既定诊断标准,在共识会议期间做出最佳估计诊断。RE-MDD先证者的一级亲属中约一半以及远亲中有四分之一患有至少一种情绪障碍,通常为MDD。正如其他寡基因、多因素疾病常见的那样,MDD的严重程度由发病年龄和发作次数反映,随着与先证者家族/遗传距离的增加而减弱。相当一部分RE-MDD先证者及其一级亲属符合其他精神疾病的诊断标准,这些疾病包括明显的情绪障碍。RE-MDD先证者的已故亲属的死亡年龄中位数比当地人群早8岁;超过40%的人在65岁之前死亡。这些死亡率统计数据的差异是由于整个寿命期内死亡年龄向更年轻的方向转变,包括一岁以内死亡个体比例增加了五倍。在RE-MDD先证者的亲属中,自杀、他杀和肝病导致的死亡比例增加了几倍。然而,心脏病、癌症和中风这三种最常见死因的排名顺序保持不变,其他死因的死亡比例差异较小。RE-MDD是一种具有高度精神科共病率的强家族性疾病,其恶性影响对患者及其家庭成员的健康和寿命有重大负面影响。