Exploring the association between serotonin transporter promoter region methylation levels and depressive symptoms: a systematic review and multi-level meta-analysis.
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引用次数: 0
Abstract
Depressive disorders result from complex interactions among genetic, epigenetic, and environmental factors. DNA methylation, a key epigenetic mechanism, is crucial in understanding depressive symptoms development. The serotonin transporter gene (5-HTT) and its polymorphisms, like 5-HTTLPR, have been extensively studied in relation to depression, yet conflicting findings regarding the association between 5-HTT promoter methylation and depressive symptoms persist, largely due to methodological differences. Thus, this systematic review and meta-analysis aims to assess (1) 5-HTT promoter methylation levels between depressed and non-depressed conditions and (2) the association between 5-HTT methylation and depressive symptoms severity. We searched PubMed, Google Scholar, and Web of Science from inception to January 15th, 2025 (PROSPERO: CRD42023355414) and performed two independent multi-level meta-analyses to answer our aims. Twenty-four trials were included in the systematic review. All reported effects carried potential for bias. The meta-analysis for depression occurrence (12 studies - 2028 subjects - 127 effects) indicated no significant effect (Hedges'g = 0.06) with moderate within- and low between-study heterogeneity. The depression severity analysis (14 studies - 2296 subjects - 116 effects) revealed a null effect size (Fisher's Z = 0.05), with no within- and moderate between-study heterogeneity. Asymmetry was detected for both meta-analyses. Moderator analyses demonstrated no significant effects of depression severity, methylation techniques, single-CpG sites, cell types assessed, age, and female percentage. This comprehensive review provides insights into the intricate interplay between 5-HTT promoter methylation and depressive symptoms. Furthermore, it offers well-considered recommendations for future research endeavors and delineates guidelines for reporting methylation research.
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.