Ghost wrote:The way I view things usually is as post-synaptic receptors only really mattering in the projection sites. The Presynaptic receptors obviously matter at the projection area and in somatodendritic autoreceptors (One of the criticisms I have always had of this theory is that it was too specific - focusing only on the 1a receptors when there are many more types in the brain as well). It has been nearly impossible to find a way to agonize those 5ht1a receptors on the right side of the synapse only. That's always how I chalked up our problems getting things to work for some people. Yohimbine worked for several if I recall.
There are selective postsynaptic 5HT1A agonists, but they are research chemicals. Nearly all serotonin receptor subtypes behave paradoxically when it comes to transcriptional adaptation. It is very difficult to predict how those receptors regulate when faced with serotonin flooding after autoreceptor desensitization (and worse: when faced with an exogenous ligand). And these receptors modulate many neurotransmitters and hormones. The serotonin system is very complex, so I stick with my past experiences with drugs, which brings me to 5HT1A and 5HT2A as the two main prominent receptors involved with
my own PSSD subtype.
Ghost wrote:Glucocorticoids no doubt play a role somewhere along the line. I'm a bit surprised though that people go into remission from mental illness if these levels remain elevated however. When tested, my levels weren't out of the ordinary. This also pushed me away from looking too much here.
People with mental illnesses often have a degree of glucocorticoid resistance. Even when they introduce supraphysiological level of corticosteroids, these patients never develop symptoms of Cushing's. Antidepressants solve this issue by modulating GR function, usually through upregulation, to trigger a negative feedback. Patients with treatment-resistant conditions don't experience this effect, and SSRIs fail as a treatment. So, I agree that GR are involved in some PSSD cases.
Many of PSSD patients, me included, have a cortisol level on the lower side. I agree with what you've said, that there are interpersonal variations when it comes to PSSD and every person would need a tailored regimen.
Ghost wrote:Meso please keep going on this! It will take some hashing out but I think with enough feedback and time you'll get some actionable findings from it. Your access to medications is key and I'm hoping you are still largely in remission. I'll get you those gene results ASAP and this summer after the MCAT I am going to go at this 1000% once again. The summer is when I always make the most research traction.
It gets very frustrating sometimes, but life is incredibly bland with PSSD around. And even on a symptomatic treatment, it's too heavy on the wallet and may not be sustainable on the longer run. I need to attempt reversing my own PSSD soon.