Unveiling causal interactions between depression and alcohol use from adolescence to young adulthood

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Abstract Submission 

Xuefei Wang¹

¹Fudan University, Shanghai, China

Xuefei Wang  
Fudan University
Shanghai, China

Depression is one of the most common mental disorders, and alcohol use disorder often co-occurs with depression. However, little is known about the direction of the relationship between the two diseases. Most of the research on alcohol use and depression has been conducted in adults, and the findings may not necessarily apply to adolescents. Our study aims to longitudinally track the relationship between alcohol use and depression from adolescence to early adulthood.

We analyzed the IMAGEN dataset at baseline (14 years old), Follow-up 1 (16 years old), Follow-up 2 (19 years old), and Follow-up 3 (23 years old) to assess the partial correlations between alcohol consumption and depression, controlling for covariates such as gender, handedness, and imaging sites. We then employed cross-lagged panel analysis and a modified Mendelian randomization analysis to investigate the causal interactions. This new MR approach employed polygenic risk scores (PRS) as the instrumental variable that integrates the contributions of multiple genetic variations while accounting for pleiotropic SNPs. In addition, we employed a mediation analysis to investigate shared neural mechanisms, extracting participants' average brain activation in regions of interest (ROIs) comprising the bilateral Inferior Frontal Cortex (IFC) and Caudate during reward anticipation in the Monetary Incentive Delay (MID) task, as well as in the Stop-Signal Task (SST). The masks in the current study with t > 5 in the contrasts of large win vs. no win in MID and stop success vs. go success in SST.

Depression and alcohol consumption frequency were significantly positively correlated at baseline (r = 0.139, p = 4.11E-10). The correlation gradually decreased over time and became negative. However, depression and harmful alcohol use remained significantly positively correlated at all time points (baseline: r = 0.106, p = 1.15E-06) (Figure 1a). Instrumental PRS of depression at both baseline and follow-up 3 showed positive correlations with alcohol abuse, while instrumental PRS for alcohol drinking at Follow-up 3 displayed a negative correlation with depression scores (Figure 1b). In the Stop-Signal Task, the left inferior orbitofrontal cortex (OFC) may mediate the positive correlation between Major Depressive Disorder Polygenic Risk Scores (MDD PRS) and harmful alcohol use (βmediation = 7.55E-4, p = 4E-3). Conversely, in the Monetary Incentive Delay (MID) task, right Caudate may mediate the negative correlation between Alcohol Polygenic Risk Scores (ALCO PRS) and dep8_FU3 (βmediation = -440, p = 0.017) (Figure 2).

Depression has a positive predictive effect on harmful alcohol use, while moderate alcohol consumption in early adulthood can alleviate depression. This mutual causal interactions could help to a better understanding and management of the relationship between alcohol consumption and depressive symptoms, ultimately enhancing the mental health of adolescents and young adults.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Early life, Adolescence, Aging ²

BOLD fMRI

FUNCTIONAL MRI

Psychiatric Disorders

Other - Depression, Alcohol Use, Adolescence, Causal interactions