Neuroanatomy of Emotion in Treatment Resistant Psychosis

描述（由申请人提供）：尽管在治疗精神障碍方面取得了相对成功，但我们对当中断时导致精神病的潜在过程知之甚少。这种缺乏理解在以下事实中特别明显：目前的药物治疗仍然使大约50%的精神分裂症/情感障碍患者具有持续的症状。更好地了解精神病的病理生理过程，特别是那些尽管治疗仍有症状的患者，对改善治疗结果至关重要。这反过来又需要更好地理解相关大脑网络通常执行的功能。重要的发现已经开始指向与精神病相关的神经生物学。检查这项工作，似乎精神病可能涉及边缘脑区域的功能障碍，通常评估刺激的情绪显着性，这种功能障碍可能需要边缘/情绪区域与前额叶/认知区域的异常相互作用。情绪显著性的建立及其产生的进一步处理似乎涉及豆状核下/基底前脑区域、内侧前额叶皮层和眶额皮层。amygda.la这些区域接受丰富的多巴胺能神经支配，对精神分裂症和情感障碍的治疗至关重要。我们假设精神病的阳性症状涉及不恰当的显著性归因，如参照妄想，而阴性症状涉及对情绪刺激的反应失败。本研究拟利用功能磁共振成像（fMRT）技术对精神分裂症/情感性精神障碍患者的情绪刺激反应进行研究，并验证以下假设：（目的1）难治性阳性症状患者的杏仁核和内侧前额叶皮质异常激活;（目的2）有缺陷/原发阴性症状的患者将无法激活眶额皮质。确定这些区域参与治疗抵抗性症状应该为更大的精神病难题提供重要的一部分，最终引导我们找到新的更好的精神病治疗策略。

DESCRIPTION (provided by applicant): In spite of relative success in the treatment of psychotic disorders, we know very little about the underlying processes which, when disrupted, lead to psychosis. This lack of understanding is particularly evident in the fact that current pharmacologic therapies still leave approximately 50 % of schizophrenic/schizoaffective patients with persistent symptoms. Better understanding of the pathophysiological processes underlying psychosis, and particularly those in patients who remain symptomatic despite treatment, will be critical to improving treatment outcomes. This in turn requires an improved understanding of the functions normally carried out by relevant brain networks. Significant findings have begun to point to a neurobiology relevant to psychosis. Examining this work, it appears that psychosis may involve a dysfunction in limbic brain regions that normally evaluate the emotional salience of stimuli, and this dysfunction likely entails abnormal interaction of limbic/emotional areas with prefrontal/cognitive areas. The establishment of emotional salience and the further processing it generates appear to involve sublenticular/basal forebrain areas, amygda.la, medial prefrontal cortex and orbitofrontal cortex. These regions receive rich doparninergic innervation and appear critical to the treatment of schizophrenia and schizoaffective disorder. We hypothesize that positive symptoms of psychosis involve the inappropriate attribution of salience, such as delusions of reference, while negative symptoms involve a failure to respond to emotional stimuli. We propose to use functional magnetic resonance imaging (fMRT) to map responses to emotionally salient stimuli in treated patients with schizophrenia/schizoaffective disorder who remain actively symptomatic, and we will test the following hypotheses: (Aim 1) Patients with treatment-resistant positive symptoms will exhibit abnormal activation of the amygdala and medial prefrontal cortex; (Aim 2) Patients with defict/primary negative symptoms will fail to activate the orbitofrontal cortex. Establishing the involvement of these regions in treatment resistant symptoms should provide an important piece of the much larger puzzle of psychosis, eventually leading us to new and better treatment strategies for psychotic disorders.