細微體質特徵異常與精神分裂症之治療阻抗

Minor Physical Anomalies and Treatment Resistance in Schizophrenia

林安省(An-Sheng Lin)

指導教授 ： 陳為堅

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.01309

摘要

目標
精神分裂症是一複雜的重大精神疾病，罹病者會有思考，知覺，言語，情感等多方面的障礙。精神分裂症的臨床病程有相當程度的變異，其中最嚴重的，即是所謂的難治型精神分裂症(treatment-resistant schizophrenia，簡稱TRS)。目前對於難治型精神分裂症的成因還不是十分了解，但過去的文獻顯示可能和神經生物，心理社會方面的因子有關。另一方面，過去的文獻指出精神分裂症患者常比一般人有較多的細微體質特徵異常(minor physical anomalies, 簡稱MPAs)，支持精神分裂症的神經發育異常假說。而細微體質特徵異常與精神分裂症的症狀、病程、神經心理功能等的關連，還有待更進一步的研究。本研究將探討細微體質特徵異常與精神分裂症之治療阻抗的關連。
方法
本研究於2010年4月至10月期間，自行政院衛生署八里療養院收集108位難治型精神分裂症病人(平均年齡44.9歲，標準差9.1歲)，並採用性別與年齡頻率匹配的方式，收集104位非難治型精神分裂症病人(平均年齡43.6歲，標準差8.6歲)作為對照組。由一位精神專科醫師進行系統化的病歷回顧，並依據2001年Conley等人提出的難治型精神分裂症標準來判定病人是否為難治型。本研究使用一套標準化的測量方式(主要參考Waldrop及Lane等人提出的量表)比較該兩組病人的細微體質特徵異常的不同，並測量兩組病人的神經認知功能。研究結果和資料分析將採用統計分析的方法來處理。
結果
研究結果顯示，與非難治型精神分裂症病人相較，難治型精神分裂症病人平均發病年齡較早(相差3.8年)，住院次數較多且持續注意力表現較差。在質性測量的部份，難治型精神分裂症病人在口部及手部有較多的細微體質特徵異常，而在量性測量的部份，難治型精神分裂症病人在下半部臉高、臉高、左右眼裂長、人中長度、上下唇長方面較非難治型精神分裂症病人增加，而在臉寬、顱高、右耳寬方面則是減少。羅吉斯迴歸分析顯示在控制年齡、性別、是否早發病的共變因子影響之下，臉部細微體質特徵異常的分數合併臉寬、下臉高、左側眼裂長對於研究個體是否屬於難治型精神分裂症有良好的預測力(ROC曲線下面積0.85)。即使在迴歸模型中加入持續注意力的預測因子，細微體質特徵異常仍保有良好的預測力。
結論
綜上所述，本研究顯示難治型精神分裂症確有較多的細微體質特徵異常且有較狹長的下半部臉型，暗示其在精神分裂症之治療阻抗可能扮演某種角色且意味著神經發育異常假說與治療阻抗的關連。

關鍵字

精神分裂症 ； 細微體質特徵異常 ； 治療阻抗 ； 難治型

並列摘要

Objective
Schizophrenia is postulated to be a neurodevelopmental disorder with varying disease courses. It was estimated that about 20% to 30% of patients with schizophrenia respond poorly to treatment. Literature reviews also indicated that treatment resistant schizophrenia (TRS) correlates with neurobiological, psychological and social factors. Meanwhile, higher rates of minor physical anomalies (MPAs) among patients with schizophrenia have been documented, supporting the neurodevelopmental model of schizophrenia. However, little is known about whether MPAs are associated with treatment outcomes. This study aimed to investigate whether there are associations between MPAs and treatment resistance in schizophrenia.
Methods
Participants were recruited from both inpatients and outpatients with schizophrenia receiving treatments in a psychiatric center in northern Taiwan during the period between April, 2010 and October, 2010. A total of 108 patients for the TRS with a mean age of 44.9 years (SD = 9.1) and 104 patients for the non-TRS group with a mean age of 43.6 (SD = 8.6) were recruited, with a frequency matching on age and sex. For each individual, a systemic chart review was conducted by a board-certified psychiatrist. Patients’ clinical information was collected to determine the status of treatment resistance according to the criteria proposed by Conley and Kelly in 2001. The patients underwent both qualitative and quantitative measurements of MPAs by a well-trained research assistant using a comprehensive scale adapted from Waldrop and Lane scales. A brief cognitive assessment using Continuous Performance Test was also done.
Results
The TRS group had an earlier mean onset age by 3.8 years, more hospitalizations and a poorer sustained attention performance than the non-TRS group. For the qualitative measures of MPAs, the TRS group had more physical anomalies in the region of mouth and hands, compared with the non-TRS group. For the quantitative measurements of craniofacial MPAs, there were significant increases in terms of lower facial height, facial height, bilateral palpebral fissure length, length of the philtrum and length of mouth, as well as significant decreases in terms of facial width, skull height, and right ear width in the TRS group. For the logistic regression analysis of treatment resistant status, a model contained the MPAs scores of mouth region, facial width, lower facial height and left palpebral fissure length with the covariates of sex, age and the binary variable of early onset had good prediction with an area under the curve of around 0.85. The prediction power the MPAs remained similar after adding a binary sustained attention deficit to the model.
Conclusions
Our results showed that the TRS group had more physical anomalies manifested mainly as a narrower facial width and longer lower facial height than the non-TRS group. These findings suggest that MPAs may play a role in the development of treatment resistance in schizophrenia and imply a neurodevelopmental mechanism underlying such resistance.

並列關鍵字

minor physical anomalies ； schizophrenia ； treatment resistance ； treatment resistant schizophrenia

參考文獻

Altamura AC, Bassetti R, Cattaneo E, Vismara S (2005) Some biological correlates of drug resistance in schizophrenia: a multidimensional approach. World J Biol Psychiatry 6 Suppl 2: 23-30.

Beck LH, Bransome ED, Jr., Mirsky AF, Rosvold HE, Sarason I (1956) A continuous performance test of brain damage. J Consult Psychol 20: 343-50.

Buckley PF, Dean D, Bookstein FL, Han S, Yerukhimovich M, Min KJ, Singer B (2005) A three-dimensional morphometric study of craniofacial shape in schizophrenia. Am J Psychiatry 162: 606-8.

Chen WJ, Chang CH, Liu SK, Hwang TJ, Hwu HG (2004) Sustained attention deficits in nonpsychotic relatives of schizophrenic patients: a recurrence risk ratio analysis. Biol Psychiatry 55: 995-1000.

Chen WJ, Hsiao CK, Hsiao LL, Hwu HG (1998a) Performance of the Continuous Performance Test among community samples. Schizophr Bull 24: 163-74.