Negative Symptoms of Schizophrenia: From Phenomenology to Targeted Treatment

精神分裂症的阴性症状：从现象学到针对性治疗

• 批准号: 7544961
• 负责人: ARIELLE D STANFORD
• 金额: $ 17.71万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7544961
• 关键词: Abnormal Cell; Adverse event; Age; Attention; Audiometry; Brain; Characteristics; Chemistry; Clinical Trials; Cognition; Cognitive; Controlled Clinical Trials; Data; Demographic Factors; Development Plans; Disease; Dose; Double-Blind Method; Dropout; Etiology; Fathers; Frequencies; Functional Imaging; Goals; Grouping; Hamilton Rating Scale for Depression; Heterogeneity; Image; Inferior; Intervention; Left; Link; Location; Maps; Mediating; Mediator of activation protein; Memory; Mentored Patient-Oriented Research Career Development Award; Movement Disorders; Neurobiology; Neurons; Outcome; Parietal Lobe; Paternal Age; Patients; Pharmaceutical Preparations; Physiology; Positioning Attribute; Prefrontal Cortex; Quality of life; Randomized; Randomized Clinical Trials; Reporting; Research; Research Design; Research Personnel; Research Training; Resistance; Resolution; Rest; Role; Safety; Sampling; Schizophrenia; Severe Acute Respiratory Syndrome; Shapes; Site; Social Functioning; Subgroup; Symptoms; Testing; Upper arm; Variant; active method; age related; career; career development; deficit syndrome; depression; depressive symptoms; design; executive function; experience; improved functioning; neural circuit; neuropsychological; novel; offspring; regional difference; relating to nervous system; repetitive transcranial magnetic stimulation; response; sex; skills; skills training; therapy development; tool; treatment site; treatment strategy

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award will provide Dr. Arielle Stanford with the training and skills needed to become an independent investigator with expertise in the development of treatments targeting the negative symptoms of schizophrenia. Negative symptoms are among the strongest predictors of poor outcome and are not very responsive to treatment. Novel treatments are needed to alleviate these symptoms and improve functioning. Most treatment studies have not focused on the large between-patient variability in phenomenology and etiology that may contribute to reduced response rates. This project will evaluate the potential utility of repetitive transcranial magnetic stimulation (rTMS) as an intervention that may test etiological hypotheses linked to heterogeneity and treat negative symptoms. While it has been difficult to meaningfully separate schizophrenia disease variants, there are subgrouping strategies that could be explored with respect to negative symptoms, including the division of patients into Deficit Syndrome (DS) and nonDS groups, and data supporting Paternal Age Related Schizophrenia (PARS) as an independent variant. Studies suggest that different types of negative symptoms map to disparate neural circuits. Thus, noninvasive focal brain stimulation may have specific advantages over medications, which lack spatial resolution. rTMS can modulate neuronal activity and produce regionally specific excitatory or inhibitory effects through modulation of local physiology and chemistry. The efficacy of rTMS may be enhanced by site-specific application targeted to patient subgroups. None of the existing studies of rTMS in schizophrenia have entailed full characterization of patients, nor has DS been considered as a response mediator. Lastly, studies of negative symptoms have only targeted the DLPFC, omitting the potential role of other cortical regions. The aims of this Mentored Patient-Oriented Research Career Development Award are to 1) to examine the efficacy and safety of rTMS as a treatment for the negative symptoms of schizophrenia and 2) to characterize responders vs. non-responders to rTMS with respect to etiological subgroup (DS vs. non-DS) and other baseline characteristics, including cognitive and demographic, using the focality of rTMS as a brain probe to test hypotheses regarding the neural underpinnings of negative symptoms. The candidate's career goal is to develop novel treatment strategies tailored to the symptom profile and schizophrenia subtype of the patient, i.e. to shape this novel intervention to the heterogeneity of schizophrenia. The career development plan will provide expertise in: 1) the neurocircuitry of negative symptoms, 2) the use of TMS as a neurobiological probe and as a treatment tool; and 3) clinical trial research design and statistical analysis. This training and research experience will position Dr. Stanford to become an independent investigator in the field of intervention development in the study and treatment of schizophrenia.

描述（由申请人提供）：这项受过指导的以患者为导向的研究职业发展奖将为Arielle Stanford博士提供成为独立研究者所需的培训和技能，该研究人员在针对精神分裂症负面症状的治疗方面具有专业知识。负面症状是预后不良的最强预测因素之一，对治疗的反应不太敏感。需要新的治疗方法来减轻这些症状并改善功能。大多数治疗研究并未集中在现象学和病因的大范围内变异性上，这可能导致反应率降低。该项目将评估重复经颅磁刺激（RTMS）的潜在效用，作为一种可以检验与异质性和治疗负面症状相关的病因假设的干预措施。尽管很难有意义地将精神分裂症疾病变异分离出来，但有一些亚组策略可以在负面症状方面探讨，包括将患者分为赤字综合征（DS）和NONDS组，以及支持父亲年龄相关的精神分裂症（PARS）的数据。研究表明，不同类型的阴性症状映射到不同的神经回路。因此，非侵入性局灶性脑刺激可能比缺乏空间分辨率的药物具有特定的优势。 RTM可以通过调节局部生理学和化学的调节来调节神经元活性，并产生特定于区域特定的兴奋性或抑制作用。通过针对患者亚组的网站特定应用可以提高RTMS的功效。精神分裂症中RTM的现有研究都没有对患者的全面表征，也不被视为反应介质。最后，负面症状的研究仅针对DLPFC，忽略了其他皮质区域的潜在作用。 The aims of this Mentored Patient-Oriented Research Career Development Award are to 1) to examine the efficacy and safety of rTMS as a treatment for the negative symptoms of schizophrenia and 2) to characterize responders vs. non-responders to rTMS with respect to etiological subgroup (DS vs. non-DS) and other baseline characteristics, including cognitive and demographic, using the focality of rTMS as a brain probe to test hypotheses关于阴性症状的神经基础。候选人的职业目标是制定针对患者症状特征和精神分裂症亚型量身定制的新型治疗策略，即将这种新颖的干预措施塑造为精神分裂症的异质性。职业发展计划将在以下方面提供专业知识：1）负面症状的神经记录，2）将TMS用作神经生物学探针和治疗工具； 3）临床试验研究设计和统计分析。这项培训和研究经验将使斯坦福大学博士成为精神分裂症研究和治疗的干预发展领域的独立研究者。