Depression and Cognitive Impairment in Transverse Myelitis

PI的长期职业兴趣是帮助阐明潜在的生物学机制 情绪调节和认知功能障碍。该职业发展奖的目标是让具有基础科学背景的主要研究者（PI）成为神经精神转化研究的临床研究者，研究免疫介导的抑郁症和自身免疫性CNS疾病的认知障碍。为了实现其目标，PI将获得神经免疫学、神经影像学和临床研究方法方面的额外培训。约翰霍普金斯医学院将为PI提供所有这些培训领域的专家指导。为了研究情绪和认知的生物学基础，将在多发性硬化症（MS）和横肌萎缩症（TM）患者中研究抑郁和认知障碍。多发性硬化症（MS）是所有慢性疾病中抑郁症发病率最高的疾病，认知障碍的患病率为50%。横肌萎缩症（TM）是一种自身免疫性疾病，如MS，但脱髓鞘病变只存在于脊髓。我们发现TM患者的严重抑郁率高于MS患者 对照组和选择性认知障碍TM科目可比他们的MS同行。 细胞因子是免疫细胞用来协调其反应的化学信使。除了它们在调节免疫系统功能中的作用之外，最近的研究表明细胞因子还影响CNS和HPA轴。在人类和动物研究中有越来越多的证据支持促炎细胞因子在介导抑郁和认知障碍中的作用。我们建议MS和TM提供了一个模型的麻黄碱介导的抑郁症和认知障碍。我们计划采用MS、TM和对照受试者的神经精神评估、细胞因子分析和磁共振波谱（MRS）来阐明与抑郁症和认知功能障碍相关的细胞因子升高和脑神经化学变化。将对受试者进行纵向随访， 如果细胞因子水平和脑代谢物的变化与情绪、认知和神经系统结果的变化平行。TM和MS受试者中抑郁的神经内分泌相关性将通过检查其HPA轴的功能来确定。我们预计，这项研究的结果将有直接的影响，MS，TM和其他中枢神经系统自身免疫性疾病的神经精神共病。这些发现可以显著扩展我们诊断、鉴别和治疗不同类型神经精神后遗症患者的能力。 自身免疫性疾病此外，这些研究有可能阐明特发性抑郁症的免疫机制，从而产生新的治疗策略。

The PI's long-term career interests are to help elucidate the biological mechanisms underlying disorders of mood regulation and cognitive function. The goal of this career development award is to allow the Principle Investigator (PI), who has a basic science background, to become a clinical investigator in neuropsychiatric translational research studying immune-mediated depression and cognitive impairment in autoimmune CNS diseases. To accomplish his goals the PI will obtain additional training in neuroimmunology, neuroimaging, and methods of clinical investigation. The Johns Hopkins School of Medicine will provide the PI with expert mentorship in all of these areas of training. In order to study the biological basis of mood and cognition, depression and cognitive impairment will be investigated in patients with Multiple Sclerosis (MS) and Transverse Myelitis (TM). Multiple Sclerosis (MS) has the highest rate of depression of any chronic disease, and a 50% prevalence of cognitive impairment. Transverse Myelitis (TM) is an autoimmune disorder like MS but with demyelinating lesions present only in the spinal cord. We found rates of severe depression in subjects with TM to be higher than those of MS controls and selective cognitive impairments in TM subjects comparable to their MS counterparts. Cytokines are chemical messengers that immune cells use to coordinate their responses. In addition to their role in modulating immune system function, recent studies have shown that cytokines also influence the CNS and the HPA axis. There is a growing body of evidence in human and animal investigations supporting a role for proinflammatory cytokines in mediating depression and cognitive impairment. We propose that MS and TM provide a model of cytokine-mediated depression and cognitive impairment. We plan to employ neuropsychiatric evaluations, cytokine profiling, and Magnetic Resonance Spectroscopy (MRS) of MS, TM and control subjects to elucidate cytokine elevations and brain neurochemical changes that correlate with depression and cognitive dysfunction. Subjects will be followed longitudinally to determine if changes in cytokine levels and brain metabolites parallel changes in mood, cognition and neurologic outcomes. Neuroendocrine correlates of depression in TM and MS subjects will be ascertained through examination of the function of their HPA axis. We anticipate that the results of this study will have direct implications for the neuropsychiatric comorbidities of MS, TM and other CNS autoimmune diseases. These findings could significantly expand our ability to diagnose, prognosticate, and treat neuropsychiatric sequelae in patients with diverse types of autoimmune disorders. Furthermore, these studies have the potential to illuminate immune mechanisms in idiopathic Major Depression that could result in novel therapeutic strategies.