Novel study discovers genes associated with depression after early life trauma

Scientists from King’s College London have discovered that three genes (FoxO1, A2M and TGF-β1) increase risk for developing depression later in life, when individuals have been exposed to early life trauma. The novel study, which was published in Molecular Psychiatry, builds on previous evidence that an individual’s genetic makeup interacts with environmental stress and leads to depression, an approach that could also be applied to other stress-related disorders.

If replicated, early screening for these genes in patients could help to identify those who would benefit from additional support from clinicians, before depressive symptoms even begin to occur.

Understanding how and why depression occurs is an urgent priority for mental health research. In the UK alone approximately three million people have been diagnosed with this condition, while the World Health Organization has predicted that depression will be the second leading cause of disability by 2020.

Experiencing trauma in childhood is a major risk factor for developing depression later in life, but not all individuals who experience trauma will develop depression. However, this study shows that such differences could be due to the interaction between genetic variants and exposure to stress.

Using a novel cross-species and cross-tissues approach, the researchers identified target genes from brain samples of rodents exposed to early life stress as well as in human blood samples from adults who had been exposed to childhood trauma. Overlapping genes were then further validated in human DNA from two independent clinical populations, from individuals in the US and Finland, resulting in the discovery of the three genes (FoxO1, A2M and TGF-β1) that were associated with increased risk for developing depression after experiencing childhood trauma. Finally, the researchers also used a cellular model of depression to show that the gene FoxO1 could functionally influence how brain cells respond to stress.

These comprehensive findings, replicated across different species, different tissues and in different clinical populations, provide very strong evidence that individuals with specific genetic variants in these three genes, especially FoxO1, are more vulnerable to develop depression if exposed to childhood trauma.

Dr. Annamaria Cattaneo, first author from the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said ‘If we could stratify individuals exposed to childhood trauma for these genetic variants to identify those with an enhanced risk of developing depression, we could also propose some preventive (pharmacological or non-pharmacological) therapies to reduce or minimise their vulnerability.’

Professor Carmine Pariante, senior author from the Stress, Psychiatry and Immunology Laboratory at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said ‘Identification of these novel genetic variants support a role of the immune system in depression, as some of the genes are directly relevant to inflammation. This will further allow us to understand why some individuals are more vulnerable to depression than others’.

This study was funded by the Medical Research Council UK.

Paper reference: Cattaneo, A et al. (2018) ‘FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses’. Molecular Psychiatry. DOI:10.1038/s41380-017-0002-4

For further media information please contact Robin Bisson, Senior Press Officer, Institute of Psychiatry, Psychology & Neuroscience, King’s College London on robin.bisson@kcl.ac.uk or 020 7848 5377.