View Full Version : Recovering from severe depression

11-18-13, 01:35 PM
Alright, I apologize now for how rambling and long this will be, but I just discovered this forum, and so far, it has been amazing and therapeutic to see that I'm not alone in this. I would love to get feedback and have a discussion about severe depression and how to recover. And given how much I've obsessively researched this, perhaps others could learn something and apply it to their own circumstances.

So, I have been pretty severely depressed for the past 9 months. I'm so sick of feeling this way. I want to get better so badly and I've been able to pull myself up a couple times only to relapse shortly after. Given the duration, I worry that my brain will remodel itself to lock in the general wiring and neurochemistry of this depressed and anxious state. I've been reading as much on adhd, depression, and sleep as I can and have learned a lot at this point. According to the serotonin-kynurenine hypothesis of depression, the precursor to serotonin, tryptophan, is shunted away from serotonin production and is diverted to kynurenine, which is likely a depressogenic and anxiogenic compound. This shift can be caused by stress and anxiety, which increase levels of the stress hormone, cortisol, which in turn activates the enzyme that takes tryptophan and puts it down the kynurenine pathway instead of the serotonin pathway thereby increasing anxiogenic and depressogenic compounds in the brain while simultaneously depleting serotonin. This hypothesis can explain a lot of the symptoms including lowered mood (due to lower serotonin), anxiety (due to kynurenine), sleep disturbances (melatonin is made from serotonin so if tryptophan is shunted away from serotonin, it is also being shunted away from melatonin), and others. Currently, SSRIs are the most prescribed antidepressants, but let's face reality--they simply do not work that well In fact, some side effects like sexual dysfunction are more common than remission of depression. This could very well be because these drugs do not address the kynurenine-serotonin hypothesis, or more accurately, only address half of it. Increasing serotonin levels in the synapses can help with depression, but if the tryptophan handling pathway is still geared toward depleting serotonin and increasing the depressogenic and anxiogenic kynurenine, then you can see why perhaps the current antidepressants don't work very well--they are based on a very old and simplistic model of depression. A model that we know can't be right because we simply suck at adequately treating depression. Also, the health care system is very biased toward just throwing pharmaceuticals at the problem. In a hyper-competitive and often socially Darwinistic society where 70% of Americans hate or have completely 'checked out' of their jobs, its no wonder its so easy to become depressed. About 80% of eighth graders have anxiety levels that would have gotten a person institutionalized 50-60 years ago. So, without addressing the causes of psychosocial stress, these stressful conditions will persist in one's life and continue to cause them to continually produce high amounts of cortisol, which could be the link between stress and depression. Additionally, this hypothesis seems to almost imply a possible positive-feedback loop in depression. Stress ---> depression/anxiety ---> more stress ---> more anxiety/depression etc. Anyway, I think breaking this positive-feedback loop could be the key to breaking a depressive episode. So, I am trying to treat myself based on this model of depression, which just resonates with me and does more to explain how I have been feeling than the simplistic theory that there is just not enough serotonin in some synapses.

Alright, so my personal bag of issues is: ADHD-combined, seasonal affective disorder (SAD), major depressive disorder (MDD), delayed sleep phase syndrome (DSPS), and I definitely have some emotional issues.

My treatment plan: vitamin D through April (for SAD), will get a phototherapy lamp (for SAD, DSPS, and ADHD), 5-HTP supplement (serotonin precursor, for MDD), and I take 0.25 mg melatonin at 6 pm, which shifts my sleep phase earlier. Oh yeah, I also take adderall xr and I really should start exercising regularly, but its hard to muster up the motivation when you're depressed. I'm trying my best to understand what's been happening to me and doing my best to hit this as hard as I can.

So, what are people's thoughts on the kynurenine-serotonin hypothesis? What have you tried in the past that has worked? What have you tried in the past that has failed? Any discussion, feedback, tips, hints, or encouragement would be greatly appreciated.

11-19-13, 02:46 AM
I really know nothing about the kynurenine-serotonin hypothesis. If I were you I would just keep checking google scholar to read new studies when they are published. You can subscribe to google alerts for that hypothesis, & then anytime that hypothesis is mentioned on the internet you will be notified.
As for exercise, there are only a couple of ways I can make myself do it. I have to play a team sport like basketball, where the game is so involving & exciting, you don't even realize you're exercising. Now that I have a bad calf, I just walk on the treadmill. I bought a tablet, & I go to a gym that has wifi and watch YouTube videos the entire time you are walking (or jogging). The key for me is distraction. Anything to distract yourself from the fact that exercise sucks, & is uncomfortable & painful while doing it.
Do you like your job?
One of the best antidepressants for me over the years has been my best friend. When we get together we laugh & have a great time. We always go hiking together, so there again, our conversation while hiking distracts me from the fact that I'm actually exercising.
As for that hypothesis, my own opinion is that depression may also involve other neurotransmitters, like the pleasure nuerotr dopamine.
The SSRI's really don't work. The only meds that have helped me have been Wellbutrin & Lamictal. Deplin (which is a high dose of Folic Acid's active ingredient) has helped me.

11-19-13, 05:21 AM
can you define what tserotonin-kynurenine hypothesis is? Im trying to understand it in layman's terms.

11-19-13, 10:25 PM
Jshect--Still a student and I hate it, but I'm at least very close to getting my degree and will be able to take an easy credit load next semester and learn things that actually interest me. Thanks for the input!

Sarahsweets--So the current theory really only deals with serotonin in any meaningful way and it states that decreased serotonin leads to and is the cause of depression. But where did the serotonin disappear off to? The serotonin-kynurenine hypothesis accounts for this and expands upon it in a way to explain why stress is a major risk factor for depression. Like the current theory, the serotonin-kynurenine hypothesis agrees that lowered levels of serotonin plays a very important role in depression. Normally, a person eats something, gets tryptophan (an amino acid) from their food, and then their body uses that tryptophan to make serotonin. Under stress, a person will eat, get tryptophan from their food, but instead of using it to make serotonin, their body uses it to make kynurenine. Kynurenine is thought to cause anxiety and depression. So, stress increases the kynurenine to serotonin ratio and a high kynurenine:serotonin ratio leads to depression.