Sokolov Aleksandr V, Lafta Muataz S, Nordberg Didi O T, Jonsson Jörgen, Schiöth Helgi B
Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
Front Psychiatry. 2024 May 15;15:1372106. doi: 10.3389/fpsyt.2024.1372106. eCollection 2024.
Depression is a major global burden with unclear pathophysiology and poor treatment outcomes. Diagnosis of depression continues to rely primarily on behavioral rather than biological methods. Investigating tools that might aid in diagnosing and treating early-onset depression is essential for improving the prognosis of the disease course. While there is increasing evidence of possible biomarkers in adult depression, studies investigating this subject in adolescents are lacking.
In the current study, we analyzed protein levels in 461 adolescents assessed for depression using the Development and Well-Being Assessment (DAWBA) questionnaire as part of the domestic Psychiatric Health in Adolescent Study conducted in Uppsala, Sweden. We used the Proseek Multiplex Neuro Exploratory panel with Proximity Extension Assay technology provided by Olink Bioscience, followed by transcriptome analyses for the genes corresponding to the significant proteins, using four publicly available cohorts.
We identified a total of seven proteins showing different levels between DAWBA risk groups at nominal significance, including RBKS, CRADD, ASGR1, HMOX2, PPP3R1, CD63, and PMVK. Transcriptomic analyses for these genes showed nominally significant replication of PPP3R1 in two of four cohorts including whole blood and prefrontal cortex, while ASGR1 and CD63 were replicated in only one cohort.
Our study on adolescent depression revealed protein-level and transcriptomic differences, particularly in PPP3R1, pointing to the involvement of the calcineurin pathway in depression. Our findings regarding PPP3R1 also support the role of the prefrontal cortex in depression and reinforce the significance of investigating prefrontal cortex-related mechanisms in depression.
抑郁症是一项重大的全球负担，其病理生理学尚不明确，治疗效果不佳。抑郁症的诊断仍然主要依赖行为学方法而非生物学方法。研究有助于早期抑郁症诊断和治疗的工具对于改善疾病进程的预后至关重要。虽然越来越多的证据表明成人抑郁症可能存在生物标志物，但在青少年中对此主题进行研究的却很少。
在本研究中，我们分析了461名青少年的蛋白质水平，这些青少年使用发展与幸福感评估（DAWBA）问卷进行抑郁症评估，该问卷是瑞典乌普萨拉开展的国内青少年精神健康研究的一部分。我们使用了由Olink Bioscience提供的带有邻近延伸分析技术的Proseek多重神经探索性检测板，随后使用四个公开可用的队列对与显著蛋白质相对应的基因进行转录组分析。
我们总共鉴定出七种蛋白质，在名义显著性水平上，DAWBA风险组之间显示出不同水平，包括RBKS、CRADD、ASGR1、HMOX2、PPP3R1、CD63和PMVK。对这些基因的转录组分析表明，PPP3R1在包括全血和前额叶皮质在内的四个队列中的两个队列中显示出名义上显著的重复，而ASGR1和CD63仅在一个队列中重复。
我们对青少年抑郁症的研究揭示了蛋白质水平和转录组差异，特别是在PPP3R1中，表明钙调神经磷酸酶途径参与了抑郁症。我们关于PPP3R1的研究结果也支持前额叶皮质在抑郁症中的作用，并强化了研究抑郁症中前额叶皮质相关机制的重要性。
