Striatal Function in Psychosis Relapse

项目摘要 精神障碍的特征通常是在疾病过程中反复复发。复发影响 职业和社会功能，可能危及病人和他人，往往需要住院 住院，推高医疗成本。事实上，复发的累积效应在治疗中起着重要作用。 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 在大多数以前的研究中没有很好地捕捉到，因为很少有研究解释了 抗精神病药物非依从性，在治疗期间的某个时间点影响大多数精神病患者 而且常常被忽视。本研究旨在探讨精神病复发的神经生物学机制 在接受长效注射（LAI）抗精神病药物治疗的个体中， 可以可靠地量化复发时间。我们将重点关注纹状体功能，因为它在大脑中起着关键作用。 精神病的病理生理学和作为抗精神病药物的靶点。具体来说，我们将进行核磁共振成像 评估纹状体功能在休息（目标1）和奖励过程中（目标2），以及中- 纹状体多巴胺传递使用神经黑色素敏感MRI（目的3）。我们将比较这些措施， LAI抗精神病药物治疗期间精神病复发个体间的横断面设计 （n=44），在LAI抗精神病药物治疗期间精神病稳定的个体（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 与接受LAI治疗的临床稳定个体相比，异常纹状体功能。如果成功，这 该项目将产生关于精神病复发的病理生理学数据，对治疗依从性无偏见。 这些数据对于开发用于预防精神病复发的急需的预后生物标志物至关重要。

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.