This post is about depression and genetics — fragile x premutation is statistically associated with depression.
That’s news.
I keep an eye on Fragile X research because there seems to be an “epigenetic” component. (Molecular wonks: I’m using the term “epigenetic” to basically mean non-Mendellian — spontaneous mutations of any sort , rather than just the methylation or activation in the strict “epigenetic” sense).
Fragile X genetics and studies on Fragile X premutation are becoming increasingly more visible.
See Time Magazine article from June 2008 , and here National Fragile X Foundation, and here UC Davis Aggie (UC Davis is home to the MIND (Medical Investigation of Neurodevelopmental Disorders) Institute, where Fragile X in all of its forms are delved into at length, large scale population genetics studies are ongoing to provide insight into the carriers of the full blown condition, as well as “premutation” carriers.
To oversimplify, Fragile X is the end of an X chromosome with little extra bits of DNA added. The extra bits are in units of three nucleotides — so it’s a “trinucleotide repeat” type of chromosomal change. The behavioral and physical symptoms are dosage-related — the more trinucleotide repeats, the more severe the disease (again to oversimplify). When you have, say, 200+ trinucleotide repeats, Fragile X symptoms are intellectual disabilities, behavior problems, low muscle tone and some physical abnormalities.
Say you have 3 copies — probably nothing to notice. But 20-30-80 copies? These “premutations” — fewer than the (about) 200+ copies for full Fragile X — that are being correlated to behavioral phenotypes.
And so at some copy-number level, you get depression. Here’s from Roberts et al. :
Major depression in females with the FMR1 (“Fragile X”) premutation may not be characterized as an episodically chronic recurrent disorder as it is in community samples and may have a genetic basis given the relationship with CGG repeat length and lack of association with all child and most demographic factors.
Roberts JE, Bailey DB, Mankowski J, Ford A, Sideris J, Weisenfeld LA, Heath TM, Golden RN. 2008. Mood and Anxiety Disorders in Females with the FMR1 Premutation. Am J Med Genet Part B.Mood and anxiety disorders in females with the FMR1 premutation 10.1002/ajmg.b.30786
Why the premutation is associated with depression, whereas the full blown mutation isn’t , is anyone’s guess. Perhaps mild gene expression alteration causes physiological conditions resembling prefrontal dementia — and the depression is really sort of apathy. Perhaps the full blown mutation has compensatory mechanisms overriding this.
Here are links to previous posts relating to Fragile X and premutations:
Actually carriers having depression isn’t that big of news. Those of us who have it have known for decades that our depression was linked to our funky gene. It’s just that the mainstream, non-fx doctors, are now talking about it and getting it….finally
Thank you for your comment, FXSmom. Agree, this isn’t well known among the non-initiated. I would have thought that “depression” was due to the stress of caring for autistic/FXR family members. Nope, statistically segregates out to even those who have no children.
I think most of us have “funk” in our genes that ebbs and flows over our lifetimes. (I ‘m co-opting your expression of “funky genes”
).
Much of mainstream medical, with its ever-shrinking resources, seems to take the approach “don’t tell me the mechanism, just tell me how to treat clinically”. So it’s a chicken-egg thing, how can you know how to treat if you don’t know the cause?
There is still some stigma associated with depression with many believing it is something of a character weakness. Part of me believed that too. Knowing the cause of it came as a relief to me and the additional anxiety and depression caused by feelings of inadequacy were avoided.
I suffered from depression and anxiety long before I knew I was a carrier of FX. Knowing the cause meant that I accepted it had a chemical basis and I persisted in finding medication and therapy that works for me.
Thanks for the comment Sueblimely (had to read your handle twice before I got it
)
Just from a crass commercial point of view, your example is exactly the reason why personalized medicine is so important. The drug cos. used to hate that idea (or they used to) because they wanted to give everyone an SSRI, whether that was the cause of the depression or not (so they sold more drug).
Like obesity, addictions, and any other behavior that has an organic basis, you need to know the basis to treat the symptom, and it’s not one size fits all. It may be one size fits most (as I suspect obesity meds will turn out to be), but probably dopamine/serotonin issues will need to be carefully diagnosed.