New genetic clues for depression

Current estimates for depression from the National Institute of Mental Health (NIMH) indicate that in any given year, 6.7% of the American population has the disease. To put that statistic in terms that are easier to grasp, that means that over 21,000,000 people have the disease in this country alone. It’s been hard to nail down what could be causing it, however.

Finally, scientists think they’ve finally found the first hard genetic links to major depressive disorder (MDD).

Depression, like most complex diseases that result from a combination of both genes and environment (e.g. diabetes, heart disease, etc.), is a difficult disease to study. For a long time, we’ve known that many people with depression have family members who also suffer from the disease and that stress or other traumatic events can intensify the disorder.

For the longest time, though, searches for genetic variants that could cause the disease came up empty. Learning from the difficulties experienced by other groups of researchers, the CONVERGE consortium (a group of scientists based in both China and the UK¹) used a different approach from previous attempts to study the genome of Han Chinese women. When they did this, they found variants in two genes, SIRT1 and LHPP².

Finding the first genetic clues for what causes depression is an enormous breakthrough to say the least. Figuring out how these genes help to cause depression in the first place is the next step. Thankfully, one of the genes that may help cause the disease in Chinese women may give us a clue about what could be causing depression in patients from other parts of the world.

SIRT1 is involved in maintaining the health of mitochondria³, which is the “power plant” of the cell. Mitochondria are instrumental in producing adenosine triphosphate (ATP), the usable form of energy for cells that we produce by breaking down sugars in food. When the mitochondria don’t function properly, the cell is in serious trouble because it doesn’t have the energy to do what it needs.

The fact that depressed individuals may have problems with mitochondria fits nicely with ideas that have been discussed by biologists and psychiatrists for a while.

The brain is highly demanding when it comes to energy production. As an organ, the brain only weighs about three pounds, but it consumes about one-fifth of the body’s energy⁴. In order to keep up with demand, the mitochondria have to be working non-stop at peak efficiency. So, if a gene variant makes the mitochondria less fit to produce energy the brain needs, it stands to reason that things like mood could be affected.

New brain imaging techniques show us regions of the brain that aren’t working normally in people with depression⁵. We know that serotonin, a chemical that helps cells in the brain communicate with one another, is also important in how the disease works. For example, selective serotonin reuptake inhibitors (SSRIs) make up a major class of medications used to treat depression and related diseases⁶, and they all work by targeting serotonin.

So are SIRT1 and LHPP the entire story when it comes to genetic links to depression? I highly doubt it.

Mitochondria and brain function are controlled by a multitude of genes, but the fact that diseases like depression could be caused in part by problems with energy production in the brain opens new avenues for research, treatments, and ultimately, cures. Findings like these are probably only the tip of the iceberg.

References

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387371/
2. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14659.html
3. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14635.html
4. http://www.scientificamerican.com/article/why-does-the-brain-need-s/
5. https://www.sciencemag.org/content/317/5839/757.full
6. http://stke.sciencemag.org/content/5/244/pe45.full