The relationship of subcortical brain volume with smoking an
Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol.

Investigators assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomization.

Mendelian randomization uses genetic variants predictive of a certain ‘exposure’ as instrumental variables to test causal effects on an ‘outcome’. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. They used summary-level data of genome-wide association studies of subcortical brain volumes and smoking and alcohol use.

- There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume and smoking more cigarettes per day decreased hippocampal volume.

- From subcortical brain volumes to substance use, there was no or weak evidence for causal effects.

The findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.