Neuroanatomy of Emotion in Treatment Resistant Psychosis

描述(申请人提供)：尽管在治疗精神障碍方面取得了相对成功，但我们对导致精神障碍的潜在过程知之甚少。这种缺乏了解的情况尤其明显，因为目前的药物治疗仍然使大约50%的精神分裂症/分裂情感患者出现持续症状。更好地了解精神病的病理生理过程，特别是那些尽管接受治疗但仍有症状的患者，将是改善治疗结果的关键。这反过来需要对相关大脑网络通常执行的功能有更好的理解。重要的发现已经开始指向与精神病相关的神经生物学。考察这项工作，似乎精神病可能涉及边缘大脑区域的功能障碍，该区域通常评估刺激的情绪突显，这种功能障碍可能导致边缘/情绪区域与前额/认知区域的异常相互作用。情绪突显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、杏仁核、内侧前额叶皮质和眶前叶皮质。这些区域接受丰富的多巴胺能神经支配，似乎对精神分裂症和分裂情感障碍的治疗至关重要。我们假设，精神病的积极症状涉及对突显的不适当归因，例如参照错觉，而消极症状涉及对情绪刺激的反应失败。我们提议使用功能磁共振成像(FMRT)来描绘仍然有活跃症状的精神分裂症/分裂情感障碍治疗患者对情绪显著刺激的反应，我们将检验以下假设：(目标1)有治疗抵抗阳性症状的患者将显示杏仁核和内侧前额皮质的异常激活；(目标2)有缺陷/原发阴性症状的患者将无法激活眼眶额叶皮质。确定这些区域参与治疗耐药症状应该会为精神病这个更大的谜团提供重要的一块，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.