PILOT STUDY OF ATOMOXETINE TO ENHANCE COGNITION IN PATIENTS WITH SCHIZOPHRENIA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管阳性症状得到了适当的控制，但许多精神分裂症患者仍存在严重的认知缺陷，限制了他们实现最佳功能能力的能力。增强前额叶皮质多巴胺能活动的药物可能是改善认知而不会恶化精神病的理想药物。临床前研究表明，托莫西汀可以增加前额叶皮质的多巴胺水平，但不能增加纹状体和伏隔核等皮质下区域的多巴胺水平。因此，我们认为，当它与稳定的抗精神病药物治疗方案一起使用时，在增强精神分裂症患者的认知方面可能非常有用。在这项拟议的研究中，我们将进行基线神经认知测试，并在精神分裂症和分裂情感障碍患者的功能磁共振成像(FMRI)期间通过工作记忆测试来测量前额叶皮质的激活。然后，患者将被随机分配到除常规剂量的抗精神病药物外，接受托莫西汀或安慰剂。托莫西汀的起始量将是每天40毫克，四周后将增加到40毫克，每日两次，然后在接下来的四周内继续使用这个剂量。在治疗4周和8周后，将进行重复的神经认知测试，只有在治疗8周后才会重复进行功能磁共振成像。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite adequate control of positive symptoms, many patients with schizophrenia suffer from severe cognitive deficits that limit their ability to realize optimal functional capacity. Medications that enhance dopaminergic activity in the prefrontal cortex may be ideal to improve cognition without worsening psychosis. Atomoxetine has been shown in pre-clinical studies to increase dopamine levels in prefrontal cortex but not in subcortical regions such as striatum and nucleus accumbens. Therefore, we believe that it may be extremely useful, when added to a stable regimen of antipsychotic medication, in enhancing cognition in patients with schizophrenia. In the proposed study, we will conduct baseline neurocognitive tests and measure activation of the prefrontal cortex by a working memory test during functional magnetic resonance imaging (fMRI) in patients with schizophrenia and schizoaffective disorder. Patients will then be randomized to receive either atomoxetine or placebo in addition to their regular dose of antipsychotic medication. The starting dose of atomoxetine will be 40 mg per day which will be increased to 40 mg bid after four weeks and then continued at this dose for the next four weeks. After four and eight weeks of treatment, repeat neurocognitive tests will be conducted and the fMRI will be repeated only after eight weeks of treatment.