Yeşiloğlu, Buket

Background/Objectives: Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), along with obstructive sleep apnea (OSA), are prevalent conditions that have serious effects on affected individuals and public health. These issues have received more attention recently, as research shows there are similar risk factors and they can influence each other by worsening symptoms and treatment response. However, there is still no clear understanding of the extent of this co-occurrence and the factors that influence it. Methods: A systematic review of comorbid OSA and mood disorders was conducted from EMBASE, Ovid MEDLINE, Global Health, and APA PsycINFO (1 January 2013–25 July 2025), with meta-analyses applying random-effects models in R (metafor). Heterogeneity, publication bias, subgroup effects, and meta-regression analyses were performed by assessing demographic, clinical, and study quality variables. Results: Out of 6221 screened studies, 23 articles met eligibility criteria, yielding 2,380,986 OSA patients, with 446,495 comorbid mood disorders (MDD = 446,290; BD = 205), and 5724 mood disorder patients (MDD = 1987; BD = 3737) with 450 comorbid OSA. All meta-analyses demonstrated a significant prevalence of comorbidity, accompanied by substantial heterogeneity. Meta-regression analyses identified mean age (β = 0.18, 95% CI 0.03–0.33, p = 0.02) and mean body mass index (β = −0.18, 95% CI −0.32 to −0.04, p = 0.01) as significant moderators of OSA prevalence. Conclusions: This meta-analysis indicates a high prevalence of comorbidity between OSA and mood disorders, including MDD and BD, with significant heterogeneity. Age and body mass index emerged as significant moderators of OSA prevalence, emphasizing the need for systematic screening and tailored approaches in both clinical practice and research.

Abstract Introduction Bipolar disorder (BD) has been associated with increased medical burden and accelerated biological aging. Long non-coding RNAs (lncRNAs) regulate molecular pathways related to cellular senescence, inflammation, and telomere maintenance, which are implicated in both BD and aging. This study examined whether aging-related lncRNA expression reflects familial vulnerability or illness-specific effects, and whether childhood trauma and lifestyle factors modulate these signatures within a gene–environment framework. Methods In this cross-sectional study, expression levels of aging-related lncRNAs, including Antisense Non-coding RNA in the INK4 Locus (ANRIL), HOX Transcript Antisense Intergenic RNA (HOTAIR), Nuclear Enriched Abundant Transcript 1 (NEAT1), Taurine Upregulated Gene 1 (TUG1), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), Growth Arrest-Specific 5 (GAS5), and Telomerase RNA Component (TERC), were measured in peripheral blood mononuclear cells (PBMCs) from individuals with bipolar disorder (BD) (n=68), siblings without BD diagnosis (SIB) (n=54), and healthy controls (HC) (n=70) using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Childhood trauma and lifestyle were assessed using the Childhood Trauma Questionnaire (CTQ) and the Healthy Lifestyle Profile II (HPLP-II). Principal component analysis generated a composite aging-related lncRNA factor. Results At the individual transcript level, NEAT1 and TERC were elevated, whereas GAS5 was reduced, in both BD and SIB relative to HC. The aging-related lncRNA composite score was higher in BD and SIB than in HC (F = 7.315, p = 0.001). Familial liability to BD (presence vs. absence of familial liability ) showed a significant main effect on the composite score (F(1,182)=8.18, p=0.005) and interacted with childhood trauma (F(1,182)=10.14, p=0.002). In multivariable models, total CTQ and physical neglect were independently associated with lower composite scores, while familial liability remained a positive predictor (all p<0.001). Conclusions Aging-related lncRNA alterations mark familial vulnerability to BD and are shaped by childhood trauma within a gene–environment interaction framework.