Ho Beng-Choon, Andreasen Nancy C, Ziebell Steven, Pierson Ronald, Magnotta Vincent
Departments of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Arch Gen Psychiatry. 2011 Feb;68(2):128-37. doi: 10.1001/archgenpsychiatry.2010.199.
Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain.
To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change.
Predictors of brain volume changes were assessed prospectively based on multiple informants.
Data from the Iowa Longitudinal Study.
Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient had 3 scans (≥2 and as many as 5) over 7.2 years (up to 14 years).
Brain volumes.
During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted.
Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.
精神分裂症患者脑部容积的渐进性变化主要被认为是由该疾病导致的。然而，近期的动物研究表明，抗精神病药物作为精神分裂症患者的主要治疗药物，也可能导致脑组织容积减少。由于抗精神病药物需长期用于精神分裂症患者，且在其他精神疾病中的使用越来越广泛，因此确定其对人脑的长期影响至关重要。
评估脑容积变化的4个潜在预测因素（病程、抗精神病药物治疗、疾病严重程度和物质滥用）的相对作用。
基于多名信息提供者对脑容积变化的预测因素进行前瞻性评估。
爱荷华纵向研究的数据。
211例精神分裂症患者，在疾病发作后不久即开始进行重复神经影像学检查，共获得674次高分辨率磁共振扫描。平均而言，每位患者在7.2年（最长14年）内进行了3次扫描（≥2次，最多5次）。
脑容积。
在纵向随访期间，抗精神病药物治疗反映了1991年至2009年的全国处方模式。随访时间越长，脑组织容积越小，脑脊液容积越大。在控制了其他3个预测因素的影响后，抗精神病药物治疗强度越大，与广泛性和特异性脑组织减少的指标相关。抗精神病药物治疗越多，灰质容积越小。在接受更多抗精神病药物治疗的患者中，白质容积的渐进性减少最为明显。疾病严重程度与组织容积减少的相关性相对较小，在调整其他变量的影响后，酒精/非法药物滥用无显著关联。
结合动物研究数据来看，我们的研究表明抗精神病药物随着时间推移对脑组织损失有细微但可测量的影响，这表明对治疗剂量、治疗持续时间及其非适应证使用进行仔细的风险效益评估非常重要。
