Luis Alameda, Victoria Rodriguez, Marta Di Forti, Edoardo Spinazzola, Giulia Trotta, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Bobes, Lieuwe de Haan, Cristina Marta Del-Ben, Charlotte Gayer-Anderson, Lucia Sideli, Peter B Jones, James B Kirkbride, Caterina La Cascia, Giada Tripoli, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Pierre-Michel Llorca, Paulo Rossi Menezes, Jim van Os, Bart P Rutten, Jose Luis Santos, Julio Sanjuán, Jean-Paul Selten, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Eva Velthorst, Hannah E Jongsma, Evangelos Vassos, Diego Quattrone, Robin M Murray, Monica Aas
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We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. 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A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. 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引用次数: 0
摘要
童年时期的逆境与精神病的各种临床症状有关;然而,遗传易感性如何形成与逆境有关的精神病理学特征尚有待研究。我们研究了来自 EU-GEI FEP 病例对照研究的 583 个首发精神病(FEP)病例的数据,包括重度抑郁障碍(MDD-PRS)、双相情感障碍(BD-PRS)和精神分裂症(SZ-PRS)的多基因风险评分;以童年创伤问卷(CTQ)总分衡量的童年逆境;以及跨诊断维度因子模型中的阳性、阴性、抑郁和躁狂精神病理学领域。基因与环境之间的相互作用被视为 PRSs 和 CTQ 总量对每个维度的乘法效应。分析对年龄、性别、10 PCA、招募地点和药物进行了调整。在 A) CTQ 和 MDD-PRS 之间观察到童年逆境和 PRS 在积极(β = 0.42,95% CI = [0.155,0.682],p = 0.004)和抑郁(β = 0.33,95% CI = [0.071,0.591],p = 0.013);B)CTQ 与 BD-PRS 在积极维度上的差异(β = 0.45,95% CI = [0.106,0.798],p = 0.010),以及 C)CTQ 与 SZ-PRS 在积极维度上的差异(β = -0.34,95% CI = [-0.660,-0.015],p = 0.040)。Bonferroni 校正后的显著性 P 值定为 0.0125。总之,尽管这项研究的力量不足,但它表明,MDD 和 BD 的遗传责任可能对童年逆境对抑郁和积极精神病维度的敏感性有调节作用。这支持了关于童年逆境是导致精神病的情感途径的假设。
The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis.
Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.
期刊介绍:
Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.