The role of MED22 and its transcriptional interactions with childhood trauma and trauma-focused psychotherapy in patients with major depressive disorder

IF 2.7 3区医学 Q1 BEHAVIORAL SCIENCES

Biological Psychology Pub Date : 2025-04-01 DOI:10.1016/j.biopsycho.2025.109039

Rosana Carvalho Silva , Elisabetta Maffioletti , Chiara Magri , Annamaria Cattaneo , Monica Mazzelli , Mattia Meattini , Marco Bortolomasi , Roberta Bazzanella , Giulia Perusi , Massimo Gennarelli , Alessandra Minelli

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引用次数: 0

Abstract

The biological mechanisms linking childhood trauma (CT) to major depressive disorder (MDD) remain unclear. Expanding on previous research linking MED22 to CT in MDD, we examined three research questions: (1) MED22's role in the relationship between CT and MDD, considering genetic (GReX) and environmental (EReX) components of gene expression regulation; (2) associations between MED22 genetic variations and personality traits like neuroticism in 177 healthy volunteers; and (3) changes in MED22 expression over time in 22 MDD patients with CT undergoing trauma-focused psychotherapy, with clinical and blood assessments at baseline (T0), 4 (T4), 8 (T8), 12 (T12), and 24 weeks (T24). For the first question, in MDD patients, MED22 GReX was associated with neglect, sexual, and emotional abuse, while EReX was associated with neglect. For the second question, in healthy volunteers, MED22 SNPs were associated with higher neuroticism (Beta=0.2284; p-value=0.008), indicating reduced stress resilience. Finally, for the third question, psychotherapy improved depressive symptoms (p < 0.001) and decreased MED22 expression (F=3.05; p = 0.03), with a treatment response effect (F= 3.44; p = 0.02) at T12. Differences in MED22 expression between responders and non-responders were observed at T4 (z_value= -2.13; p = 0.040), T8 (z_value=-3.85; p = 0.0004), and T12 (z_value= -2.93; p = 0.007). Baseline transcript levels were positively associated with relapse (τ=0.390; p = 0.037) and were higher (p = 0.026) in non-remitters, suggesting potential for detecting relapse. MED22 reductions from T0 to T8 were associated with improved cognitive symptoms (τ= 0.345; p = 0.040). Transcript reductions at T12 were associated with improvements in neurovegetative (τ=0.362; p = 0.027) and anxiety symptoms (τ= 0.324; p = 0.040). Genetic and environmental factors may influence stress responses.

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MED22的作用及其转录相互作用在重度抑郁症患者的童年创伤和创伤为重点的心理治疗

儿童创伤（CT）与重度抑郁症（MDD）之间的生物学机制尚不清楚。在先前将MED22与MDD中的CT联系起来的研究基础上，我们研究了三个研究问题：(1)MED22在CT和MDD之间的关系中的作用，考虑基因表达调控的遗传（GReX）和环境（EReX）成分；(2) 177名健康志愿者MED22基因变异与神经质等人格特征的关系；(3) 22例接受创伤性心理治疗的MDD CT患者的MED22表达随时间的变化，并在基线（T0）、4 （T4）、8 （T8）、12 （T12）和24周（T24）进行临床和血液评估。对于第一个问题，在重度抑郁症患者中，MED22 GReX与忽视、性虐待和情感虐待有关，而EReX与忽视有关。对于第二个问题，在健康志愿者中，MED22 snp与较高的神经质相关(Beta=0.2284；p值=0.008)，表明应力恢复能力降低。最后，对于第三个问题，心理治疗改善了抑郁症状（p <； 0.001），降低了MED22的表达(F=3.05；p = 0.03)，治疗反应效果显著(F= 3.44；p = 0.02)在T12。T4时，有应答者与无应答者MED22表达差异(z_value= -2.13；p = 0.040),T8 (z_value=-3.85；p = 0.0004),T12 (z_value= -2.93； = 0.007页)。基线转录物水平与复发呈正相关(τ=0.390；P = 0.037)，非汇款者更高（P = 0.026），提示有可能检测到复发。从T0到T8的MED22降低与认知症状改善相关(τ= 0.345； = 0.040页)。T12时转录物减少与神经营养改善相关(τ=0.362；P = 0.027)和焦虑症状(τ= 0.324； = 0.040页)。遗传和环境因素可能影响应激反应。

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来源期刊

Biological Psychology 医学-行为科学

CiteScore

4.20

自引率

11.50%

发文量

146

审稿时长

3 months

期刊介绍： Biological Psychology publishes original scientific papers on the biological aspects of psychological states and processes. Biological aspects include electrophysiology and biochemical assessments during psychological experiments as well as biologically induced changes in psychological function. Psychological investigations based on biological theories are also of interest. All aspects of psychological functioning, including psychopathology, are germane. The Journal concentrates on work with human subjects, but may consider work with animal subjects if conceptually related to issues in human biological psychology.