[ErikVandeWater]

> Our knowledge of the genetics, however, is incomplete. Krystal noted that studies of twins suggest that genetics may account for 40% of the risk of depression. Yet the currently identified genes seem to explain only about 5%.

I see the value in analyzing genetics for depressive genes, but I also consider that how the genes interact with our environment that play a role. For example, if the state of women's rights around the world returned to where it was 200 years ago, it would likely appear a genetic cause of depression is related to having two X chromosomes. To wit - is the issue with the genes themselves, or is it that those with the genes are somehow repressed by the way society works?

[asdff]

Gene by environment interactions are super important for understanding how genotypes affect fitness in context. Change your environment to the open ocean instead of on land, for example, and you can readily see how your genes now hurt your chances for survival instead of improve them.

That being said, there's a lot to the genetic compotent of disease risk beyond just changes to the sequence of protein coding genes. How much protein that gene produces can be affected by a number of factors, such as the presence of singe nucleotide polymorphisms (changes to one site in the DNA) that may be well outside the gene region in the genome, but are a binding region for a transcription factor or an enhancer that drives expression of that gene and therefore dramatically lowers (or increases) the protein produced. You can also have epigenetic changes that similarly effect gene expression, but these are not reflected anywhere in the genomic sequence since these represent changes to the proteins that package DNA in the nucleus, not to the DNA itself.

[zeroonetwothree]

Women have 2x the rates of depression as men. But is there any reason to think that 200 years ago it was even more so?

I think we overestimate the impact of external factors on our internal mental states. That's why the typical treatment for depression is CBT (literally changing your thoughts and behaviors) and not "improve your external situation".

[asdff]

At the same time, there's only so much to improve your external situation, especially if you are dealing with hard facts sort of situations (e.g. chronic health problems or terminal illness, poverty). If your source of depression is something external you can do something to improve, your therapist will definitely recommend you moving away from whatever that is (e.g. a toxic work environment or an abusive partner). The reason why we encourage cbt is that it gives you some tools in the mean time, as sometimes the external factors driving your depression are going to be difficult or impossible to change.

[ErikVandeWater]

> Women have 2x the rates of depression as men. But is there any reason to think that 200 years ago it was even more so?

That's interesting. I would have thought men would have it more since it's an abnormality, and with only 1 X chromosome, men are much more frequently abnormal.

When I said "If the state of women's rights around the world returned to where it was 200 years ago," I meant if women who currently had normal human rights lost them. In that case we would see a major increase in depression among women, the point being that depression would be explained much more clearly by genetic factors, even though the genes didn't change; the interaction between the genes and the world changed.

> I think we overestimate the impact of external factors on our internal mental states.

We definitely do. And the external factors that affect our happiness the most are often the least controllable.

[asdff]

I think that's in part due to the fact that women are an oppressed group in this world. Even in this country, the rhetoric used against women by certain politicians is abhorrant, and startlingly accepted by a huge swath of the population. There are politicians who want teenagers to carry their rapists baby to term; we've had a rapist president and now there's a rapist sitting on the supreme court bench. Then you have a huge swath of people who still believe in the patriarchal mid century views towards women, or who have raised sons who continue to believe that crap and saddle that behavior on their partners, perpetuating mistreatment just like how racism continues to be perpetuated. Minorities are similarly at higher risk for chronic depression than whites.