Hormones and Metabolic Profiles in Relation to Adolescent Depression ：A Prospective Follow-up study of Twin Families

本計畫為二年期追蹤計畫之第一年研究，主要研究目的是為瞭解賀爾蒙、新陳代謝指 標變化與青少年憂鬱及相關行為問題之相關的涵義，即藉由結構式模型建構來評估基因、 共享環境、非共享環境對賀爾蒙、新陳代謝指標與青少年憂鬱之相關的貢獻。相關文獻指 出青春期階段的賀爾蒙變化與新陳代謝指標與青少年憂鬱的致病機轉有密切的關係，但是 未有研究深入探討形成這些相關的基因與共同環境的作用，故本計畫擬針對於2002-2005 年為探討胰島素敏感性與Beta 細胞功能之可能遺傳貢獻所建立的252 個雙胞胎（手足）世 代及其雙親的家庭，進行關於賀爾蒙與新陳代謝指標變化與青少年憂鬱的遺傳流行病學分 析。該世代的總參加人數共為1127 人，包括雙胞胎指標個案380 人、三胞胎指標個案20 人 (其中一對三胞胎的一位指標個案未參加)，手足配對指標個案110 人、其他手足138 人， 雙親479 人。 本計畫原本擬以三年的時間，針對在計畫申請時已蒐集到之180 雙胞胎(手足)家庭， 在第一年進行賀爾蒙與新陳代謝指標的基線值檢測，並追蹤45 個家庭；第二年則預計追 蹤90 個家庭，第三年上半年再追蹤45 家，然後在下半年時以全部追蹤資料進行分析。目 前本計畫執行期限先被核准為二年，加上世代家庭在前述計畫執行完畢後增加為252 家， 因此，我們的執行目標也隨之作相關的調整。特別是本計劃大多的收案個案皆是在學的學 生，只能在假日進行追蹤，在二年期間事實上無法完成252 個雙胞胎（手足）世代家庭的 追蹤。因此，對於未能在兩年內完成追蹤者, 將來需在第三年時再提計劃來執行。 至2005 年5 月止，本計畫已針對512 位雙胞胎或手足配對完成五項賀爾蒙之基線值 檢測；並且針對252 個世代家庭，我們已完成155 (61.5 ％)個雙胞胎（手足）家庭的資料 更新，其中有41 個雙胞胎（手足）家庭目前尚無法追蹤，包括拒絕追蹤（21 家）、無法取 得聯繫（16 家）、空號或搬家（4 家），其餘的家庭則陸續安排合適的受檢時間。我們在執 行計畫的第一年中，已針對252 個雙胞胎（手足）世代及其雙親的家庭所貯存之冷凍血液 檢體進行賀爾蒙之檢測，包括:腎上腺皮質內泌(cortisol)、DHEA(dehydroepiandrosterone)、 瘦素(leptin)、雌二醇(estradiol)、睪固酮(testosterone)，並以基線時所收集的憂鬱症狀進行 雙胞胎分析。此外，我們也開始進行追蹤研究，即參加個案須完成口服葡萄糖耐受性試驗、 賀爾蒙與新陳代謝指標的測量，並接受追蹤訪談，評估工具包]括自填式之青少年問卷與父 母填寫的問卷，以及精神疾病的結構式訪談。雖然本計畫因收案機構需重新規劃硬體環 境，而須配合更換、重新設置收案地點，但是此項不預期的變更並未嚴重影響預定的進度， 我們目前共完成45 個雙胞胎（手足）家庭追蹤訪談與血液檢測的工作，預期至7 月底應可完成50 家以上。整體而言，目前計畫的執行符合原本的計畫進度。利用現有的資料， 我們將評估賀爾蒙、新陳代謝指標變化與青少年憂鬱及其相關行為問題之相關，並進行雙 胞胎分析以了解遺傳與環境因素之影響。Changes in hormones and metabolic profiles during adolescence have been associated with depression in this developmental period. However, previous studies could not distinguish between genetic influences and shared environmental influences on these associations. Although twin studies are an ideal design for this purpose, few had collected blood sample and conducted a thorough examination on hormones and metabolic indexes. In this study we plan to conduct a twin-family analysis on 252 twin/sib-pair families that were established for investigating potential genetic contribution to insulin sensitivity and beta cell function during 2002-2005. The cohort consisted of 1127 individuals, including 190 twin pairs, 7 triplets (one member of one triplet wasn’t recruited), 55 sib-pairs, 138 non-proband siblings, and 479 parents The original proposal was aimed to examine the relationship of hormones and metabolic profiles with adolescent depression among 180 twin/sib-pair families in a 3-year follow-up schedule. At the first year, the baseline measurement of hormones and metabolic profiles will be tested using the stored blood samples. Besides, a total of 45 twin/sib-pair families will be followed-up for oral glucose tolerance test and psychiatric interview as well as self-report questionnaires at the same period. We planned to complete the follow-up assessment among another 90 families at the second-year study period. In the last year we will complete the follow-up assessment on the remaining 45 twin/sib-pair families. The present study, however, was approved for 2-year duration. Besides, at the completion of the aforementioned study, i.e., insulin sensitivity and beta cell function study, the recruited cohort was expanded to 252 twin/sib-pair families. Because most of the probands can participate in the follow-up examination only during weekends or summer/winter recess, it is practically not feasible to accomplish the follow-up of the whole cohort in 2-year period. In the future, we’ll apply for a third year plan to complete the follow-up of the 252 families. As of May, 2005, among 252 cohort families, we have contacted 155 (61.5 ％) twin/sib-pair families and successfully followed and interviewed 45 families. In the first year, we have tested the stored blood sample of the twin/sib-pair families for the baseline hormones, including cortisol, dehydroepiandrosterone, leptin, estradiol, and testosterone among 512 twin/sib-pair probands. The research site was relocated due to the reconstruction of original research building. The recruitment timeline, however, was in progress as scheduled. Structural equation modeling as well as correlated frailty models will be used to estimate the contributions of genes, common environment, and nonshared environment to adolescent depression in these twin-families