Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels

IF 4 Q2 NEUROSCIENCES
Fabiana Corsi-Zuelli , Gary Donohoe , Siân Lowri Griffiths , Cristina M. Del-Ben , Andrew J. Watson , Tom Burke , Paris A. Lalousis , Declan McKernan , Derek Morris , John Kelly , Colm McDonald , Saahithh R. Patlola , Carmine Pariante , Nicholas M. Barnes , Golam M. Khandaker , John Suckling , Bill Deakin , Rachel Upthegrove , Maria R. Dauvermann
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引用次数: 0

Abstract

Background

Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations.

Methods

We evaluated whether higher plasma interleukin 6 (IL-6) levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing early (BeneMin [Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism], n = 201, 72.8% male) and established (iRELATE [Immune Response & Social Cognition in Schizophrenia], n = 94, 67.3% male) schizophrenia cohorts. Using structural equation modeling in a subsample (iRELATE: n = 42, 69.0% male; BeneMin: n = 102, 76.5% male) with data on structural brain metrics (cortical thickness and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in early and established schizophrenia samples combined and in early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose.

Results

Higher plasma IL-6 levels were related to more severe depressive symptoms in early schizophrenia (p < .05) and negative symptoms in established schizophrenia (p < .05). Structural equation modeling findings in early and established schizophrenia samples combined and early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (p > .05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (p < .05).

Conclusions

Our results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes.
精神分裂症早期和确诊阶段的抑郁和阴性症状:整合脑结构改变、认知表现和血浆白细胞介素6水平
精神分裂症患者抑郁和阴性症状与不良的功能预后相关。认知缺陷、脑皮质厚度和体积减少以及炎症可能导致抑郁和阴性症状,但药物治疗和疾病进展可能混淆这些关联。方法我们评估血浆白细胞介素6 (IL-6)水平升高是否与精神分裂症患者更严重的阴性或抑郁症状相关,并利用早期(BeneMin[米诺环素对精神分裂症阴性症状的益处:程度和机制],n = 201, 72.8%男性)和建立(iRELATE[免疫反应&;精神分裂症患者的社会认知[n = 94, 67.3%男性]。使用结构方程模型在一个子样本(iRELATE: n = 42, 69.0%男性;BeneMin: n = 102, 76.5%男性),结合大脑结构指标(皮质厚度和体积)、一般认知能力和血浆IL-6水平的数据,我们评估了这些变量与早期和晚期精神分裂症合并和仅早期精神分裂症样本中抑郁和阴性症状严重程度之间的相互关系。所有的分析都根据性别、年龄和氯丙嗪当量剂量进行了调整。结果血浆IL-6水平升高与早期精神分裂症患者抑郁症状加重相关(p <;.05)和已确诊精神分裂症的阴性症状(p <;. 05)。在早期和已建立的精神分裂症样本中,结构方程模型研究结果表明,较高的血浆IL-6水平、大脑结构指标和一般认知表现之间的相互关系不能预测抑郁和阴性症状的严重程度(p >;. 05)。较高的血浆IL-6水平和较低的一般认知表现与大脑指标降低相关(p <;. 05)。结论血浆IL-6水平升高与抑郁及阴性症状的严重程度存在不同程度的相关性。未来在更大样本中确定炎症水平升高的工作可能允许对有不良结果风险的亚组进行分层和个性化干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biological psychiatry global open science
Biological psychiatry global open science Psychiatry and Mental Health
CiteScore
4.00
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审稿时长
91 days
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