From my reading and personal experience with depression, there are three broad suggested root causes:
1. Physical root causes. The primary of these is thyroid. If it is thyroid, the good news is that thyroid medication is usually pretty effective I think. Other possibilities could be low iron, menopause, etc. I'm not a doctor, so don't take my advice, but IMHO these kinds of causes should be considered and ruled out. When the underlying physical cause goes away, the depression should go away too.
2. Endogenous. This is sort of a subcategory of (1), but I separate it out because some people, including many doctors, believe that people's brain chemistry can just get whacked out for no apparent reason. Most of these same people think that treating this with meds (like zoloft and other SSRI's) is the right thing to do. I have not heard anyone claim that endogenous depression can be self-correcting, so most people who believe this will expect the person to be on meds the rest of their life. Personally I am not convinced of this theory but I know that many people believe quite strongly in it.
3. Psychological. Maybe your SO is disappointed that the life you're leading now is not what she expected, or maybe she has regrets that she never took up skydiving, or maybe she resents you not picking up your socks and putting them in the laundry but doesn't know how to tell you. I'm just making stuff up, but the point is that maybe there's something she sees as "wrong" that you don't (that could be why she's depressed and you're not!). Introspection and/or counseling and/or talking/listening might help, but this takes a lot of time, effort, and patience.
One other comment. If your wife is on an SSRI such as Zoloft and then goes off of it, and experiences symptoms that are similar to depression, it could be antidepressant withdrawal instead of a return of the original depression. For a complete discussion, I suggest both you and she read "The Antidepressant Solution" by Glenmullen, a Harvard-trained M.D. who agrees that antidepressants are good in certain circumstances.
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