Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status

IF 3.7 2区医学 Q1 PSYCHIATRY

Journal of psychiatric research Pub Date : 2024-09-19 DOI:10.1016/j.jpsychires.2024.09.020

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引用次数: 0

Abstract

Background

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented.

Methods

We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n = 7 and n = 13, respectively).

Results

At baseline, we discovered an increased expression of TADA2B in hyperphagic MDD with the significant enrichment of 72 gene ontology pathways mainly related to inflammation. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD and discovered the upregulation of CCDC196 and the downregulation of SPATA33 in hyperphagic MDD. Gene ontology enrichment analysis after stress exposure showed pathways related to ribosomal activity. Limitations: The present findings are tempered primarily by the limited sample size, which requires independent replication of this exploratory study. However, stringent methods controlling for false positive findings mitigate the risk associated with sample size limitations.

Discussion

Limitations notwithstanding, findings suggest that hyper- and hypophagic MDD is associated with divergent RNA expression profiles in peripheral blood that are amplified by exposure to a controlled stress test. Our findings in a well-controlled study provide evidence for peripheral markers of a relevant endophenotype of MDD.

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抑郁症患者食欲亢进和食欲减退的转录组特征差异与炎症状态有关

背景重度抑郁障碍（MDD）是一种病因复杂的异质性疾病，通常表现为不同的食欲表型，包括食欲亢进型 MDD（以食欲增加为特征）和食欲减退型 MDD（以食欲减退为特征），这两种表型与包括心脏代谢紊乱在内的合并症密切相关。食欲亢进与非典型抑郁、应激激素信号减弱、促炎症状态、嗜睡和较差的临床预后有关。方法我们利用批量 RNAseq 对外周血 RNA 图谱进行了一项探索性研究，研究对象为未服药的多食和低食 MDD 患者（分别为 7 人和 13 人）。结果我们发现，基线时，多食 MDD 患者 TADA2B 的表达增加，72 个主要与炎症相关的基因本体通路显著富集。此外，我们利用马斯特里赫特急性应激任务（Maastricht Acute Stress Task）揭示了高噬性 MDD 和低噬性 MDD 的应激相关转录组特征，发现高噬性 MDD 中 CCDC196 上调，SPATA33 下调。应激暴露后的基因本体富集分析显示了与核糖体活性相关的通路。局限性：目前的研究结果主要受到样本量有限的影响，需要对这项探索性研究进行独立复制。讨论尽管存在局限性，但研究结果表明，高嗜酸性和低嗜酸性 MDD 与外周血中不同的 RNA 表达谱有关，而这些 RNA 表达谱在暴露于受控压力测试时会被放大。我们在一项控制良好的研究中的发现为 MDD 相关内表型的外周标记物提供了证据。

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

Journal of psychiatric research 医学-精神病学

CiteScore

7.30

自引率

2.10%

发文量

622

审稿时长

130 days

期刊介绍： Founded in 1961 to report on the latest work in psychiatry and cognate disciplines, the Journal of Psychiatric Research is dedicated to innovative and timely studies of four important areas of research: (1) clinical studies of all disciplines relating to psychiatric illness, as well as normal human behaviour, including biochemical, physiological, genetic, environmental, social, psychological and epidemiological factors; (2) basic studies pertaining to psychiatry in such fields as neuropsychopharmacology, neuroendocrinology, electrophysiology, genetics, experimental psychology and epidemiology; (3) the growing application of clinical laboratory techniques in psychiatry, including imagery and spectroscopy of the brain, molecular biology and computer sciences;