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The causal interplay between depression and alcohol use from adolescence to young adulthood: a Mendelian randomization study

BackgroundDepression is often comorbid with alcohol use problems, and sex differences may further complicate this interplay.MethodsWe conducted a longitudinal study using a large European adolescent cohort assessed at ages 14 (baseline, BL), 16 (follow-up 1, FU1), 19 (follow-up 2, FU2), and 23 (foll...

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Main Authors: Wang, Xuefei (Author) , Xiang, Shitong (Author) , Kang, Jujiao (Author) , Zhai, Rongquan (Author) , Zheng, Chen (Author) , Banaschewski, Tobias (Author) , Bokde, Arun L. W. (Author) , Brühl, Rüdiger (Author) , Desrivières, Sylvane (Author) , Flor, Herta (Author) , Garavan, Hugh (Author) , Gowland, Penny (Author) , Grigis, Antoine (Author) , Heinz, Andreas (Author) , Martinot, Jean-Luc (Author) , Paillère Martinot, Marie-Laure (Author) , Artiges, Eric (Author) , Nees, Frauke (Author) , Orfanos, Dimitri Papadopoulos (Author) , Paus, Tomáš (Author) , Poustka, Luise (Author) , Smolka, Michael (Author) , Hohmann, Sarah (Author) , Holz, Nathalie E. (Author) , Vaidya, Nilakshi (Author) , Walter, Henrik (Author) , Whelan, Robert (Author) , Schumann, Gunter (Author) , Jia, Tianye (Author) , Feng, Jianfeng (Author)
Format: Article (Journal)
Language:English
Published: 27 January 2026
In: Psychological medicine
Year: 2026, Volume: 56, Pages: 1-11
ISSN:1469-8978
DOI:10.1017/S0033291725102444
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1017/S0033291725102444
Verlag, kostenfrei, Volltext: https://www.cambridge.org/core/journals/psychological-medicine/article/causal-interplay-between-depression-and-alcohol-use-from-adolescence-to-young-adulthood-a-mendelian-randomization-study/4583E359127958770DBE08975B117FD9
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Author Notes:Xuefei Wang, Shitong Xiang, Jujiao Kang, Rongquan Zhai, Chen Zheng, Tobias Banaschewski, Arun L. W. Bokde, Rüdiger Brühl, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Antoine Grigis, Andreas Heinz, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Michael N. Smolka, Sarah Hohmann, Nathalie Holz, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Imagen Consortium, Tianye Jia and Jianfeng Feng
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Summary:BackgroundDepression is often comorbid with alcohol use problems, and sex differences may further complicate this interplay.MethodsWe conducted a longitudinal study using a large European adolescent cohort assessed at ages 14 (baseline, BL), 16 (follow-up 1, FU1), 19 (follow-up 2, FU2), and 23 (follow-up 3, FU3). Depression and alcohol use were measured using standardized behavioral scales. Cross-lagged analysis, improved Mendelian randomization (MR) analysis, and mediation analysis were conducted to infer the causal interplay.Results2110 adolescents were included at baseline (49% male). Depression and alcohol consumption demonstrated a significant positive correlation (rBL = 0.094, pBL = 1.58E-05, 95% CI = [0.052, 0.137]), which gradually diminished over time and eventually became significantly negative. Depression and alcohol use problems remained strongly correlated across three timepoints (r > 0.074, p < 6.76E-03). Cross-lagged analysis suggested that depression predicted future alcohol use problems: βBL-FU1 = 0.058, p = 0.021, 95% CI = [0.009, 0.108]; βFU2-FU3 = 0.142, p = 8.34E-07, 95% CI = [0.113, 0.263]. MR analyses confirmed this causal interplay (rmean = 0.043, longitudinal ppermuation < 0.001). Interestingly, MR analyses also indicated that alcohol consumption might alleviate depression (rmean = −0.022, longitudinal ppermutation = 0.043), particularly in females at FU3, of which the anxiety status and the personality trait neuroticism largely mediated the effect. These findings were validated in an independent matched sample (N = 562) from Human Connectome Project.ConclusionsDepression may predict future alcohol use problems, whereas moderate alcohol consumption might alleviate depressive symptoms, especially in females.
Item Description:Gesehen am 03.02.2026
Physical Description:Online Resource
ISSN:1469-8978
DOI:10.1017/S0033291725102444

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