Genetic overlap between comorbid anxiety-depression, stress responses and brain function: a multi-omics approach

Anxiety and depression are the most common psychiatric disorders. Combined anxiety and depression has worse health outcomes than either condition alone and merits further investigation.

We have recently discovered that the heritability of a combined indication of anxiety and depression is greater than any of these two indications alone.

We want to know whether the genetic influence on comorbid anxiety-depression could be due to differences in stress responses and baseline levels of molecules circulating in blood.

To this end, we are going to collect blood before and after a psychosocial stress task in identical and fraternal twin pairs that are concordant or discordant for anxiety-depression.

Using this design, our first aim is to estimate the genetic correlation between anxiety-depression on the one hand and stress related levels of gene transcripts, proteins and metabolites on the other.

The second aim is to determine if the same genetic factors that explain individual variation in the blood levels of these molecules also explain differences in levels of glutamate and GABA in the brain, as measured with magnetic resonance spectroscopy.

The third aim is to investigate whether a polygenic index for combined indication of anxiety and depression predicts baseline levels of metabolites and proteins in a large sample of twins in the Swedish Twin Registry.

The results will give insight into how genetic influences on anxiety-depression are mediated by molecules in blood and brain.