Environmental Factors in Cognition and Neurobiology of Early Onset Schizophrenia

早发性精神分裂症认知和神经生物学中的环境因素

• 批准号: 8411964
• 负责人: Konasale M Prasad
• 金额: $ 17.58万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411964
• 关键词: Address; Adolescent; Adult; Affect; Antibodies; Antipsychotic Agents; Biological; Biological Assay; Blood specimen; Brain; Chemicals; Chronic; Cognition; Cognitive; Cognitive deficits; Common Cold; Data; Data Collection; Databases; Development; Disease; Double Stranded DNA Virus; Encephalitis; Environmental Risk Factor; Ethanolamines; Evaluation; Exposure to; Funding; Future; Geographic Locations; Goals; Herpes Labialis; Herpesvirus 1; Hospitals; Human; Image; Impaired cognition; Impairment; Individual; Infection; Infectious Agent; Lead; Life; Life Cycle Stages; Light; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maternal Exposure; Measures; Membrane; Memory; Minority; Morbidity - disease rate; Mothers; National Institute of Mental Health; Neonatal; Nervous system structure; Neurobiology; Neurocognitive; Neuropil; Onset of illness; Outcome; Pattern; Pharmaceutical Preparations; Phase; Phenotype; Phospholipids; Phosphorus; Pilot Projects; Placebos; Prefrontal Cortex; Pregnancy; Prevention strategy; Protons; Public Health; Recording of previous events; Refractory; Regulation; Relative (related person); Research Personnel; Sampling; Schizophrenia; Serotyping; Serum; Short-Term Memory; Simplexvirus; Strategic Planning; Stress; Testing; Thick; Time; Variant; Virus; Weight; Woman; abstracting; age related; base; brain morphology; cingulate cortex; cognitive change; cohort; cost; cost effective; design; disability; early onset; effective therapy; executive function; gray matter; improved; neurodevelopment; neuropsychological; neurotropic; novel; novel therapeutics; phosphoethanolamine; postnatal; pregnant; prenatal; prenatal exposure; prevent; prospective; repository; severe mental illness; valacyclovir; visual learning

DESCRIPTION (provided by applicant): Abstract: The goal of this project is to characterize a potentially treatable factor associated with cognitive impairments in subjects with early onset schizophrenia (EOS). EOS is a relatively less well studied form of severe mental illness with more severe cognitive impairments and poorer long term outcomes compared to the adult onset schizophrenia (AOS). Because of early onset, individuals with EOS suffer from more severe and protracted disability. An important contributing factor to poor long term outcome in schizophrenia is cognitive impairments. Since these cognitive deficits are refractory to currently prescribed antipsychotics, there is an urgent need to examine factors associated with cognitive impairments in SZ. More importantly, the disease onset in EOS occurs during an active phase of neurodevelopment. Therefore, it is logical to examine the patterns of exposure including prenatal exposure that may have a bearing on neurodevelopment associated with cognitive deficits. Human studies including ours suggest that exposure to Herpes Simplex Virus, subtype 1 (HSV1) may be one of them. HSV1 is a double stranded DNA virus that causes common cold sores and requires lodging in the nervous system for its life cycle. In the US, nearly 60% of pregnant mothers and 45% of adolescents (12-19 years) are exposed to this virus. Majority of individuals exposed to HSV1 develop chronic infection and only a minority develop encephalitis. Earlier studies have consistently associated cognitive impairments and reduced grey matter volume in the prefrontal cortex among AOS subjects exposed to HSV1. We observed longitudinal changes in cognitive impairments and grey matter loss in AOS subjects exposed to HSV1. Interestingly, AOS subjects treated with an anti-herpes medication (Valacyclovir) added to an anti- psychotic showed improvement in working memory, verbal memory and visual learning compared to those who received placebo and an antipsychotic. This proposal seeks to examine the association of cognitive impairments, morphometric and membrane chemical abnormalities in subjects with EOS (aim 1) and to explore the patterns of timing of exposure with these phenotypes (aim 2). To accomplish aim 2, we will capitalize on our access to the pregnancy, delivery and neonatal data along with banked blood samples in a set of repositories at the Magee Women's Hospital (MWH). The largest of the databases contains data and blood samples on more than 110,000 mothers. This data is supplemented by prospective ldata and biological samples on more than 3000 mothers collected under different federally funded projects (PI: Dr. Simhan and Dr. Roberts). Drs. Hyagriv Simhan is the director of the MWH repository and PI on his federally funded projects is a co-investigator on this project to facilitate access to the repository. Dr. James Roberts is a consultant on this project who will make them available for this study. Combining the prospective data collection with access to the repository is the most cost effective and rapid approach to characterize timing of exposure to a potentially treatable factor. The latter may pave the way for future studies on potentially preventive strategies.

摘要：本项目旨在研究与早发性精神分裂症（EOS）患者认知障碍相关的潜在可治疗因素。与成人精神分裂症（AOS）相比，EOS是一种相对较少被研究的严重精神疾病，具有更严重的认知障碍和更差的长期预后。由于发病早，EOS患者会遭受更严重和持久的残疾。导致精神分裂症长期预后不良的一个重要因素是认知障碍。由于这些认知缺陷对目前处方的抗精神病药物是难治性的，因此迫切需要检查与SZ认知障碍相关的因素。更重要的是，EOS的发病发生在神经发育的活跃阶段。因此，检查暴露模式是合乎逻辑的，包括产前暴露，可能对与认知缺陷相关的神经发育有影响。包括我们在内的人类研究表明，暴露于1型单纯疱疹病毒（HSV1）可能是其中之一。HSV1是一种双链DNA病毒，可引起普通的唇疱疹，其生命周期需要在神经系统中栖身。在美国，近60%的孕妇和45%的青少年（12-19岁）暴露于这种病毒。暴露于1型单纯疱疹病毒的大多数人发展为慢性感染，只有少数人发展为脑炎。早期的研究一致表明，暴露于HSV1的AOS受试者的认知障碍和前额皮质灰质体积减少有关。我们观察到暴露于HSV1的AOS受试者的认知障碍和灰质损失的纵向变化。有趣的是，与那些接受安慰剂和抗精神病药物的人相比，接受抗疱疹药物（Valacyclovir）和抗精神病药物治疗的AOS受试者在工作记忆、言语记忆和视觉学习方面表现出改善。本研究旨在研究EOS患者的认知障碍、形态测量学和膜化学异常之间的关系（目的1），并探索这些表型的暴露时间模式（目的2）。为了实现目标2，我们将利用我们获得妊娠、分娩和新生儿数据的机会，以及马吉妇女医院（MWH）一组储存库中储存的血液样本。其中最大的数据库包含超过11万名母亲的数据和血液样本。这些数据由不同联邦资助项目（PI: Simhan博士和Roberts博士）收集的3000多名母亲的前瞻性数据和生物样本补充。Drs。Hyagriv Simhan是MWH储存库的负责人，他的联邦资助项目的PI是该项目的共同研究者，以促进对储存库的访问。詹姆斯·罗伯茨博士是该项目的顾问，他将为这项研究提供这些数据。将预期数据收集与对存储库的访问相结合，是描述潜在可治疗因素暴露时间的最具成本效益和最快速的方法。后者可能为今后研究可能的预防战略铺平道路。

项目成果

Insight and neurocognitive functioning in bipolar subjects.

双相情感障碍受试者的洞察力和神经认知功能。

• DOI: 10.1016/j.comppsych.2014.04.016
• 发表时间: 2015
• 期刊: Comprehensive psychiatry
• 影响因子: 7.3
• 作者: Shad,MujeebU;Prasad,Konasale;Forman,StevenD;Haas,GretchenL;Walker,JonD;Pisarov,LiubomirA;Goldstein,Gerald
• 通讯作者: Goldstein,Gerald