精神分裂症之菸鹼酸皮膚貼片紅腫反應異常與高家族負荷之關聯性

Abstract

目的：在先前的研究中，我們曾報告在精神分裂症患者及其家庭成員中之異常菸鹼酸皮膚貼片紅腫反應有家族聚集之現象。然而，尚未有研究探討此異常之紅腫反應是否與精神分裂症之家族負荷有關。本研究是比較兩類精神分裂症家庭之病人及親屬的菸鹼酸紅腫反應，即多發性家庭（家庭中至少有一對發病手足）及單發性家庭（核心家庭中僅有一位罹病成員）。 方法：研究個案為來自多發性家庭的病人及其一等親屬（311位罹患精神分裂症或分裂精感性疾患之指引個案，180位雙親與52位無病手足）、來自單發性家庭的病人及其一等親屬（176位指引個案，260位雙親與80位無病手足），以及90位正常對照個案。我們使用三種不同濃度之菸鹼酸貼片（0.001M、0.01M與0.1M），貼附於前臂皮膚上五分鐘，於移去貼片後五、十及十五分鐘時為紅腫程度評分（0，1，2及3分）。 結果：和來自單發性家庭的對比個案相較下，多發性家庭病人及其非精神病性之一等血親屬均有較為減弱之紅腫反應，而且此差異在使用濃度0.1M之菸鹼酸貼片時最為顯著，在此濃度下，來自多發性家庭的23-57%病人、27-56%父母及19-40%無病手足未呈現紅腫反應，相較之下，單發性家庭的對應個案未呈現紅腫反應之比例則分別為5-29%、3-17%及5-18%，而正常對照則是0-30%。此皮膚紅腫反應在三組之間存在一梯度：正常對照組最強，其次為單發性家庭成員，多發性家庭成員之反應為最弱。 結論：來自多發性家庭之精神分裂症病人及其無病親屬有較高之家庭負荷，同時菸鹼酸皮膚貼片紅腫反應亦更為異常。此項發現有助於未來精神分裂症遺傳病因之研究。

Objective: We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known whether this abnormal niacin response is associated with familial loading for schizophrenia. This study compared niacin response in subjects from families with a sib-pair with schizophrenia (multiplex families) and those from families with only one member affected (simplex families). Method: Subjects were schizophrenia patients and their first-degree relatives from multiplex families (311 probands with schizophrenia or schizoaffective disorder, 180 parents, and 52 non-affected siblings) and simplex families (176 schizophrenia probands, 260 parents, and 80 non-affected siblings) as well as 90 healthy comparison subjects. Niacin patches of three concentrations (0.001M, 0.01M, 0.1M) were applied to the forearm skin, and the flush response was rated at 5, 10 and 15 minutes, respectively, with a 4-point scale. Results: More blunted response to topical niacin was shown in schizophrenia probands and their nonpsychotic relatives from multiplex families than their counterparts from simplex families. The greatest degree of differentiation between groups were revealed using 0.1M of niacin, with nonflush response in 23-57% of probands, 27-56% of parents, and 19-40% of siblings from multiplex families in contrast to 5-29%, 3-17% and 5-18% of their counterparts from simplex families, respectively, as well as in 0-30% of normal controls. Conclusions: Flush response to skin niacin is more impaired in schizophrenia patients as well as their relatives from families with higher loading for schizophrenia. This finding might be useful for future genetic dissection of schizophrenia.