Preventive strategies in schizophrenia: a preclinical study

精神分裂症的预防策略：临床前研究

• 批准号: 359922117
• 负责人: Professorin Dr. Christine Winter
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie (CCM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/359922117?language=en
• 关键词: Preventive; strategies; schizophrenia; preclinical; study

Schizophrenia (SZ) is a chronic neuropsychiatric disorder that affects approximately 1% of the population worldwide. With a 10-30% treatment failure rate alternative therapeutic approaches are continuously being sought including the possibility of preventing the occurrence of full-blown SZ symptoms. Since dysfunctional antioxidant defense system and/or neuroinflammation have been suggested as potential mechanisms underlying the neuroprogression in SZ, early interventions with antioxidants and anti-inflammatory drugs have emerged as candidates for preventing the development of SZ but this has not been investigated. The present study uses the well validated poly I:C rat model of SZ to i) test the hypothesis that the anti-oxidant and anti-inflammatory compounds N-acetylcysteine, Omega-3 fatty acids or Minocycline will prevent the emergence of behavioral and neurobiological deficits phenotypic of SZ; ii) determine whether the emergence of such abnormalities is preceded by inflammatory and/ oxidative abnormalities; iii) investigate whether the preventive capacity of these interventions is associated with the prevention of inflammatory and/or oxidative abnormalities. The study will include two projects according to the developmental stage of the delivered early intervention, i.e. adolescence or pregnancy. It will further include a comprehensive evaluation of the preventive efficacy of these early interventions at three levels: a behavioral level, a neurobiological level (comprising brain metabolic activity and biochemical assessments) and an oxidative stress/inflammatory level. Levels will be investigated at different developmental windows from early adolescence to adulthood. This will allow us to establish the developmental trajectory of oxidative/ inflammatory abnormalities and ascertain whether such abnormalities i) precede and thus can serve as biomarkers of behavioral abnormalities, or ii) develop in response to the disease process. In both cases, the major question will be whether these processes may be halted by early interventions. Our study will have a strong translational perspective, providing proof-of-concept results for the future development of clinical trials using preventive anti-oxidant and anti-inflammatory treatment strategies in SZ and relevant biomarkers that may predict outcome.

精神分裂症（SZ）是一种慢性神经精神疾病，影响全球约1%的人口。由于治疗失败率为10-30%，人们正在不断寻求替代治疗方法，包括预防全面SZ症状发生的可能性。由于抗氧化防御系统功能失调和/或神经炎症已被认为是SZ神经进展的潜在机制，抗氧化剂和抗炎药物的早期干预已成为预防SZ发展的候选药物，但尚未对此进行研究。本研究采用验证良好的多I:C大鼠SZ模型来验证抗氧化和抗炎化合物n -乙酰半胱氨酸、Omega-3脂肪酸或米诺环素可以预防SZ行为和神经生物学缺陷表型的出现；Ii)确定这些异常的出现是否先于炎症和/氧化异常；Iii)调查这些干预措施的预防能力是否与预防炎症和/或氧化异常有关。该研究将包括两个项目，根据所交付的早期干预的发展阶段，即青春期或怀孕。它将进一步包括在三个层面对这些早期干预措施的预防效果进行全面评估：行为层面、神经生物学层面（包括脑代谢活动和生化评估）和氧化应激/炎症层面。将在从青春期早期到成年期的不同发育窗口期研究其水平。这将使我们能够建立氧化/炎症异常的发展轨迹，并确定这些异常是否i)发生并因此可以作为行为异常的生物标志物，或者ii)在响应疾病过程中发展。在这两种情况下，主要的问题将是这些过程是否可以通过早期干预来停止。我们的研究将具有强大的翻译视角，为SZ的预防性抗氧化和抗炎治疗策略以及可能预测结果的相关生物标志物的临床试验的未来发展提供概念验证结果。