精神病前驅期或發病早期之患者在未受抗精神病藥治療/停藥後之泌乳激素濃度的偏異：四週追蹤研究

Abstract

背景與目的 高泌乳激素血症是常見的傳統抗精神病藥物副作用之一，而過往針對處在前驅期或發病早期的精神病患者研究中，有部分研究結果顯示精神病患者在疾病初期尚未受到抗精神病藥物影響時，就有泌乳激素偏高的現象，但尚有其他研究結果與此相異。此研究主要探討精神病患者在首次發作或在疾病高危險前驅期且未受抗精神病藥物濃度影響/或僅受短期藥物影響時，病人的泌乳激素濃度與性別、年齡配對的健康受試者相比，是否有偏異的情況；再繼續探討泌乳激素濃度的變化與治療前後病人的正性、負性精神病症狀的相關，進一步釐清泌乳激素在此疾病機轉中所扮演的角色。 方法 此研究樣本來自國立台灣大學醫學院附設醫院之收案研究計畫：精神分裂症異質性之神經生物學研究：基因變異與神經生物學指標之區辨 (The Neurobiological Study on Heterogeneity of Schizophrenia: Genetic Variations and Neurobiological Differentiations, SONPOS)，並從中納入49位精神病早期且從未用過抗精神病藥物或僅短期暴露抗精神病藥的患者，與49位經性別、年齡配對的健康受試者，每位病人皆會追蹤4週，同時屬於病例對照之研究與病例追蹤之研究。每位病人皆會接受兩次正性及負性症狀評量表評估、基線未給藥時及治療28天時抽血以進行後續泌乳激素血漿濃度測定。共有19位高危險前驅期精神病患者及30位首次發病精神病患納入研究，所有的患者在進入研究後會接受Aripiprazole 4週治療。 結果 在所有病人與其配對的健康受試者中，女性的病人 (平均濃度 ± 標準差：17.8 ± 9.4) 與其對照組(19.7 ± 14.1; P = 0.4) 在未受抗精神病藥物影響時都沒有明顯差異；但男性病人 (10.2 ± 6.8) 則較對照組 (14.6 ± 6.6; P = 0.0082) 顯著地低。但將高危險前驅期精神病患者與首次發病精神病患兩組的泌乳激素進行比較，則在任何時間點都沒有差異。此外，使用Spearman相關性檢定則發現，疾病早期的精神病患者在使用aripiprazole四周後，泌乳激素改變的程度與病人在用藥後第28天的正性症狀有顯著的負相關，且男女性別都有相似的結果 (男性: r = -0.45, P = 0.03; 女性: r = -0.56, P = 0.003)。 結論 此研究發現泌乳激素在疾病初期不同嚴重程度的病人間並未有濃度上的差異，但在男性病人中發現其泌乳激素濃度顯著的比性別、年齡配對的健康對照組來的低，且病人在用aripiprazole四周後若泌乳激素濃度掉越多，病人在第28天的正性症狀分數則越高，此結果可能可以幫助提醒臨床醫師在開立藥物時，定期監測病人泌乳激素濃度變化，以給予更適當的治療。

Background Recent studies indicated that prolactin levels might be elevated in antipsychotic-naïve patients with prodromal or early stage for psychosis. However, subsequent studies reported conflicting results. This study aims to examine whether there were aberrations in the plasma prolactin levels in patients at ultra-high risk (UHR) for psychosis as well as in patients with first-episode psychosis (FEP) in comparison with age- and sex-matched healthy controls. Methods Patients diagnosed as either at UHR for psychosis or FEP at National Taiwan University Hospital were eligible for this study if they did not receive any antipsychotics or had only brief exposure to antipsychotics but underwent washout for 7 days before blood drawing. Patients’ symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). For each patient, an age- and sex-matched healthy control was recruited from the community residents or hospital employees. A total of 19 UHR, 30 FEP, and 49 healthy controls were recruited. All of patients were followed for 4 weeks after using aripiprazole at baseline. Results Among 49 patients and their matched healthy controls, the prolactin levels (ng/ml) in the female patients (mean ± SD: 17.8 ± 9.4) was not different from its controls (19.7 ± 14.1; P = 0.4 for Wilcoxon signed rank test), whereas the prolactin levels in the male patients (10.2 ± 6.8) was lower than its controls (14.6 ± 6.6; P = 0.0082 for Wilcoxon signed rank test). However, when stratified by diagnosis, the prolactin levels in FEP or UHR were not different from that of the controls in both sex. Spearman’s correlation revealed that negative correlation between change in prolactin levels from the 28th day to baseline and PANSS positive scores in both sex (male: r = -0.45, P = 0.03; female: r = -0.56, P = 0.003). Furthermore, the results were concurrent when pooled the both sex. Conclusions Patients at either prodromal or early-stage of psychosis were found to have lower prolactin levels than their individually matched healthy controls, with the lowering in prolactin levels being more prominent in male patients. After treating patients with aripiprazole for 4 weeks, a greater decline in prolactin levels was associated with higher positive symptoms on the 28th day. Our findings indicate that prolactin level in the early-stage psychotic illness may be a useful marker for the clinical management of these patients receiving treatment with aripiprazole.