Striatal Function in Psychosis Relapse

项目总结 精神障碍的特点通常是在病程中反复复发。复发影响 职业和社会功能，可能危及患者和其他人，通常需要住院治疗 住院，推高了医疗成本。事实上，复发的累积效应在 从长远来看，精神病患者的生活质量。精神病复发的病理生理学 在以前的大多数研究中都没有被很好地捕捉到，因为很少有研究解释 抗精神病药物不依从性，这会在治疗过程中的某个时候影响大多数精神病患者 而且常常不被注意到。在这项建议中，我们旨在研究精神病复发的神经生物学机制。 在接受长效可注射(LAI)抗精神病药物治疗的患者中，药物依从性在 复发的时间可以可靠地量化。我们将重点关注纹状体功能，因为它在 精神病的病理生理学，并作为抗精神病药物的靶点。具体来说，我们将进行核磁共振 评估纹状体在静息状态下的功能(目标1)和奖赏处理过程中的纹状体功能(目标2)，以及中- 纹状体多巴胺传递的神经黑素敏感磁共振成像(目标3)。我们将在以下方面比较这些措施 LAI类抗精神病药物治疗期间精神病复发患者的横断面设计 (n=44)，在接受LAI抗精神病药物治疗期间症状稳定的个人(n=44)和健康 对照组(n=32)。我们的一般假设是，经历复发的个体将表现出更大程度的 LAI治疗中纹状体功能异常与临床稳定个体的比较。如果成功，这将是 该项目将产生关于精神病复发的病理生理学的数据，对治疗依从性没有偏见。 这些数据对于开发急需的预防精神病复发的预后生物标记物至关重要。

PROJECT SUMMARY Psychotic disorders are often characterized by recurrent relapses over the course of illness. Relapses impact occupational and social functioning, may endanger the patient and others, and often require inpatient hospitalization, driving up healthcare costs. In fact, the cumulative effect of relapses plays a major role in the quality of life of individuals with psychotic disorders in the long run. The pathophysiology of psychosis relapse has not been well captured in most previous research, as few studies account for the confounder of antipsychotic drug non-adherence, which affects most patients with psychosis at some point during treatment and is often unnoticed. In this proposal, we aim to study the neurobiological mechanisms of psychosis relapse in individuals treated with long acting injectable (LAI) antipsychotics, for whom medication adherence at the time of relapse can be reliably quantified. We will focus on striatal functioning, given its critical role in the pathophysiology of psychosis and as a target of antipsychotic drugs. Specifically, we will conduct MRI assessment of striatal functioning at rest (Aim 1) and during reward processing (Aim 2), as well as of meso- striatal dopamine transmission using neuromelanin sensitive MRI (Aim 3). We will compare these measures in a cross-sectional design between individuals with psychosis relapse during treatment with LAI antipsychotics (n=44), individuals who are symptomatically stable during treatment with LAI antipsychotics (n=44) and healthy controls (n=32). Our general hypothesis is that individuals experiencing relapse will show greater degree of aberrant striatal functioning compared with clinically stable individuals on LAI treatment. If successful, this project will generate data about the pathophysiology of psychosis relapse unbiased for treatment adherence. Such data are critical to develop much needed prognostic biomarkers for relapse prevention in psychosis.