Integrating psychological models with biological pathways in psychosis

将心理模型与精神病的生物学途径相结合

• 批准号: MR/W027720/1
• 负责人: Monica Aas
• 金额: $ 125万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW027720%2F1
• 关键词: Integrating; psychological; models; biological; pathways

Schizophrenia is a complex phenotype characterized by reality distortion, cognitive impairments, and often negative symptoms. Bipolar disorders are characterized by high and low mood with or without psychotic features. Although the prevalence of schizophrenia and bipolar disorders are relatively low, they account for a tremendous personal, economic, and societal burden and people with these disorders have 15 years shorter life expectancy compared to the general population. The recent development of polygenic risk calculations has opened a new avenue for studying the underlying genetic susceptibility while excluding biases related to the selection of specific candidate genes. A polygenic risk score can be computed based on sizeable genome-wide association studies (GWAS) performed for a given phenotype (an individual's observative traits) and summarises genome-wide genotype data into a single variable that measures genetic liability to the disorder, or the trait being studied. Such a polygenic risk score might, in turn, be studied together with environmental risk factors that increase the susceptibility to schizophrenia or bipolar disorders and/or the severity of the clinical expression of these disorders. In other words, that there are individuals who would develop schizophrenia or bipolar disorders only when both genetic liability and environmental exposure (here childhood adverse events) are present but would not develop schizophrenia or bipolar disorders when either genetic liability or environmental exposure is present alone. The proposed study has impact on patient care and a stratified medicine approach: To be able to predict who is more vulnerable of developing a severe mental illness following childhood adverse events can have huge impact on the society as well as for the individual. It has recently been shown that if childhood trauma was prevented, 30% of severe mental illness could be avoided. Moreover, patients with schizophrenia and bipolar disorders who report childhood adverse events respond less well to treatment, have poorer functioning, and shorter telomeres (a marker of accelerated ageing) highlighting the pivotal need to understand if this group has a specific biological pathway that could be pharmacological targeted which we aim to clarify as part of this project. In the long run this knowledge can help improve specialized medicine by focusing on specific biological pathways affected by early life events and prediction models for disease outcomes and ageing.

精神分裂症是一种复杂的表现型，其特征是现实扭曲、认知障碍和经常出现的阴性症状。双相情感障碍的特点是情绪高涨和低落，伴有或不伴有精神病性特征。虽然精神分裂症和双相情感障碍的患病率相对较低，但它们造成了巨大的个人、经济和社会负担，而且与一般人群相比，这些疾病患者的预期寿命要短15年。多基因风险计算的最新发展为研究潜在的遗传易感性开辟了新的途径，同时排除了与特定候选基因选择有关的偏见。多基因风险评分可以基于对给定表型（个体的观察性性状）进行的大规模全基因组关联研究（GWAS）来计算，并将全基因组基因型数据总结为一个单一变量，该变量测量对该疾病或正在研究的性状的遗传倾向性。反过来，这种多基因风险评分可能会与增加精神分裂症或双相情感障碍易感性和/或这些疾病临床表现严重程度的环境风险因素一起进行研究。换句话说，有些人只有在遗传倾向和环境暴露（这里是儿童不良事件）同时存在的情况下才会发展为精神分裂症或双相情感障碍，而在遗传倾向和环境暴露单独存在的情况下则不会发展为精神分裂症或双相情感障碍。这项拟议的研究对病人护理和分层医学方法有影响：能够预测谁更容易在童年不良事件后发展为严重的精神疾病，这对社会和个人都有巨大的影响。最近的研究表明，如果儿童创伤得到预防，30%的严重精神疾病可以避免。此外，报告儿童期不良事件的精神分裂症和双相情感障碍患者对治疗的反应较差，功能较差，端粒较短（加速衰老的标志），突出了了解这一群体是否具有可作为药理学靶点的特定生物学途径的关键需求，我们的目标是澄清作为该项目的一部分。从长远来看，这些知识可以通过关注受早期生活事件影响的特定生物途径以及疾病结果和衰老的预测模型来帮助改进专业医学。

项目成果

Telomere length and verbal learning in bipolar disorders.

双相情感障碍的端粒长度和语言学习。

• DOI: 10.1016/j.jad.2023.07.087
• 发表时间: 2023
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Mlakar V

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.

• DOI: 10.1007/s00127-023-02513-0
• 发表时间: 2023-10
• 期刊: SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
• 影响因子: 4.4
• 作者: Sideli, Lucia;Aas, Monica;Quattrone, Diego;La Barbera, Daniele;La Cascia, Caterina;Ferraro, Laura;Alameda, Luis;Velthorst, Eva;Trotta, Giulia;Tripoli, Giada;Schimmenti, Adriano;Fontana, Andrea;Gayer-Anderson, Charlotte;Stilo, Simona;Seminerio, Fabio;Sartorio, Crocettarachele;Marrazzo, Giovanna;Lasalvia, Antonio;Tosato, Sarah;Tarricone, Ilaria;Berardi, Domenico;D'Andrea, Giuseppe;Arango, Celso;Arrojo, Manuel;Bernardo, Miguel;Bobes, Julio;Sanjuan, Julio;Santos, Jose Luis;Menezes, Paulo Rossi;Del-Ben, Cristina Marta;Jongsma, Hannah E.;Jones, Peter B.;Kirkbride, James B.;Llorca, Pierre-Michel;Tortell, Andrea;Pignon, Baptiste;de Haan, Lieuwe;Selten, Jean-Paul;Van Os, Jim;Rutten, Bart P.;Bentall, Richard;Di Fort, Marta;Murray, Robin M.;Morgan, Craig;Fisher, Helen L.
• 通讯作者: Fisher, Helen L.