Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Schizophr Res. 2011 Jul;129(2-3):156-62. doi: 10.1016/j.schres.2011.03.026. Epub 2011 Apr 15.
Dysfunction of the frontal lobe is considered to be central to the pathology of schizophrenia. However, the nature of these abnormalities is unclear, in particular whether they are affected by treatment. In an earlier functional MRI study of our group we found dorsolateral prefrontal lobe (DLPFC) dysfunction to be present in medication-naive first-episode patients. In this follow-up study, we investigated whether treatment with atypical antipsychotics had an effect on DLPFC functioning, and whether (change in) DLPFC functioning was related to treatment response. Twenty-three medication-naive, first-episode male schizophrenia patients and 33 matched healthy controls were scanned at baseline and were re-scanned after 10 weeks, while performing a modified Sternberg working-memory task. We specifically investigated the effect of practice on brain activation, defined as the signal change between a novel and practiced working-memory task. After the baseline scan, patients were treated with atypical antipsychotics. Based on their symptom change after ten weeks, patients were divided into responders and non-responders We found DLPFC function did not change after 10 weeks in healthy controls or in patients who received treatment. However, while patients who responded to treatment did not differ from controls, non-responders showed a reduced practice effect in the DLPFC that was present already at baseline, which did not change after treatment. A reduced practice effect in the DLFPC at baseline was found to be predictive of poor treatment response at 10 weeks. These results suggest that prefrontal lobe dysfunction reflects a distinct neuropathological substrate in a subgroup of treatment non-responsive schizophrenia patients.
额叶功能障碍被认为是精神分裂症病理的核心。然而，这些异常的性质尚不清楚，特别是它们是否受到治疗的影响。在我们小组的早期功能磁共振成像研究中，我们发现未经药物治疗的首发精神分裂症患者存在背外侧前额叶（DLPFC）功能障碍。在这项后续研究中，我们研究了使用非典型抗精神病药物治疗是否对 DLPFC 功能有影响，以及（DLPFC 功能的）变化是否与治疗反应相关。23 名未经药物治疗的首发男性精神分裂症患者和 33 名匹配的健康对照者在基线时进行扫描，然后在 10 周后重新扫描，同时进行改良的斯滕伯格工作记忆任务。我们特别研究了练习对大脑激活的影响，大脑激活定义为新的和经过练习的工作记忆任务之间的信号变化。基线扫描后，患者接受非典型抗精神病药物治疗。根据 10 周后症状的变化，患者被分为反应者和非反应者。我们发现，在健康对照组或接受治疗的患者中，10 周后 DLPFC 功能没有变化。然而，虽然对治疗有反应的患者与对照组没有差异，但非反应者在 DLPFC 中已经存在的练习效应减少，在治疗后没有改变。在 DLFPC 中，基线时的练习效应减少被发现是 10 周时治疗反应不佳的预测因素。这些结果表明，前额叶功能障碍反映了治疗无反应的精神分裂症患者亚组中的一种独特的神经病理学基础。
