Psychological medicine · 2026
The causal interplay between depression and alcohol use from adolescence to young adulthood: a Mendelian randomization study.
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Wang Xuefei, Xiang Shitong, Kang Jujiao, Zhai Rongquan, Zheng Chen, Banaschewski Tobias, Bokde Arun L W, Brühl Rüdiger, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny, Grigis Antoine, Heinz Andreas, Martinot Jean-Luc, Martinot Marie-Laure Paillère, Artiges Eric, Nees Frauke, Orfanos Dimitri Papadopoulos, Paus Tomáš, Poustka Luise, Smolka Michael N, Hohmann Sarah, Holz Nathalie, Vaidya Nilakshi, Walter Henrik, Whelan Robert, Schumann Gunter, IMAGEN Consortium, Jia Tianye, Feng Jianfeng
Аннотация
BACKGROUND: Depression is often comorbid with alcohol use problems, and sex differences may further complicate this interplay.
METHODS: We 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.
RESULTS: 2110 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.
CONCLUSIONS: Depression may predict future alcohol use problems, whereas moderate alcohol consumption might alleviate depressive symptoms, especially in females.
METHODS: We 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.
RESULTS: 2110 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.
CONCLUSIONS: Depression may predict future alcohol use problems, whereas moderate alcohol consumption might alleviate depressive symptoms, especially in females.