早期環境因子、神經心理功能、與精神分裂症之家庭遺傳負荷

Abstract

目的：比較單個精神分裂症個案家庭、多個精神分裂症個案家庭、健康對照家庭在早期環境因子的分佈情況。在早期環境因子的暴露之下，比較已知為精神分裂症內在表現型的神經心理功能在不同家庭的表現，探討家庭遺傳負荷的趨勢。 方法：參與研究的個案年齡範圍為20歲到40歲，個案母親必須可以提供生病及健康個案的懷孕、分娩、新生兒及生活事件等早期環境因子的資料。本研究將家庭分成精神分裂症家庭及健康對照組家庭，在精神分裂症家庭中又分為單一個案家庭，多個個案家庭(家庭內病人數大於一個)，精神分裂症的患者是透過台大醫院、市立療養院、桃園療養院等北部地區醫院轉介收集而來，對照組則來自台大醫院的健檢中心。每個個案皆參與Wisconsin Card Sorting Test (WCST)、連續注意力測驗(Continuous performance test CPT)兩種神經心理功能測驗。利用ANOVA進行連續變項的統計檢定；早期環境因子、神經心理功能與精神分裂症家庭遺傳負荷的比較則藉由Mixed effects model regression進行評估。 結果：在三組不同家庭中健康手足與健康手足為家裏面第一個出生兒的比例分別為多個個案家庭生病手足與健康手足為20.6%，34.5%，單一個案家庭生病手足與健康手足為 35.4%，29%，健康對照家庭為43.4%，健康對照家庭個案為第一個小孩的比例明顯偏高。在十四項接受評估的產科併發症及相關孕產事件當中，子癇前症，臍帶繞頸，陰道出血、羊膜過早破裂、分娩時間大於36小時、雙胞胎有產科併發症、孕期小於37週、緊急剖腹產、臍帶脫垂、臀位產、使用產鉗、出生體重小於2500公克、早產兒保溫箱、及其他異常疾病，在精神分裂症的家庭中生病手足與健康手足之間相互比較並無統計上顯著差異，但是兩組精神分裂症的家庭中，健康手足發生產科併發症的比例皆比生病手足略低，而精神分裂症家庭生病手足與健康對照家庭的比較中，多個個案家庭的比例較其他兩組為低。在神經心理功能方面，在Wisconsin Card Sorting Test (WCST)方面，在測量受試者維持正確規則的能力上，多個個案家庭明顯低於單一個案家庭及健康對照家庭。連續注意力測驗(Continuous performance test CPT)，多個個案家庭在敏感度指標(d’=2.09)較單一個案家庭(d’=2.14)與健康對照家庭(d’=3.74)為差，而單一個案家庭表現也較對照組為差。 結論：在多個個案家庭中，產科併發症發生的比例小於單一個案家庭與對照家庭，在神經心理功能方面上，多個個案家庭的表現也較單一個案家庭與對照家庭為差，而單一個案家庭表現也較對照組為差，有可能是因為家庭遺傳負荷不同使得有較多精神分裂症個案的家庭受早期環境因子影響較少，且因為遺傳負荷不同所以，從比例上來看，可以發現遺傳負荷越大的家庭在神經心理功能表現上越不理想的趨勢。

Objective: To examine the relations of early environmental factors to schizophrenia of different genetic loadings. We set out to assess whether schizophrenia patients of simplex family, schizophrenia patients of multiplex family, and normal controls were different in the distributions of the early environmental factors, and whether differences in early environmental exposures were further associated with those neuropsychological functionings that have been postulated to be endophenotype of schizophrenia. Methods: The study consisted of three groups of subjects: the simplex families (148 schizophrenic probands and 131 of their first-degree relatives), the multiplex families (73 schizophrenic probands and 29 of their first-degree relatives), and controls (n=83). The participants were interviewed in person by trained research assistants using a structured instrument, the Diagnostic Interview for Genetic Studies (DIGS), and were administered two sessions of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). In addition, the mothers of every family were also interviewed for information about the early environmental experiences of each offspring using scales on pregnancy history and obstetric complications. Results: The distribution of individual complications of pregnancy and labor were not different between schizophrenic probands and their unaffected siblings in each type of simplex and multiplex family. We separate obstetric complications from antepartum and intrapartum. The result adjusted by birth order and gender is significant in “Intrapartum” (p=0.02). The expected result is significant in the expression of neuropsychological function like WCST and CPT in the schizophrenia family and control family. The comparison of WCST and CPT between probands and healthy siblings of multiplex family are not different, but it is significant in the simplex family. The scores of schizophrenic families are worse than the control family’s. Conclusion: The distribution of proband of multiplex family is different to the simplex family and control family. The result maybe is due to different genetic loading in three families.