@Cotcha
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033019/
Look what I found. Earlier in the thread you said that things would just downregulate with excess 5-HT right?
But this paper claims:
"Although description of the functional attributes of the serotonin polymorphism have been contradictory (Karg et al., 2011), clinical data would prompt us to suspect that the short allele is associated with an inability of the serotonin transporter to cope with excess synaptic 5-HT in the somatodendritic raphe area but this statement remains speculative."
So the *short* serotonin transporter supposedly has trouble with high 5-HT (though they admit its contradictory)
"The expected compensation of autoreceptor down-modulation to enhanced peri-raphe 5-HT is overwhelmed by the magnitude of agonism during “flooding” and putatively exceeds the capacity of the autoreceptor to sufficiently “down-modulate” (Blier et al., 1998) (Figure (Figure3),3), a contention supported by 5-HT1A irreversible KO rodent studies described below (see Bipolar Versus Unipolar Depression: Data from Animal Models)."
This paper is in reference to SSRI non response. But if MDMA releases tons of serotonin, could a similar thing happen with the short serotonin allele?
..And then of course presumably excess 'bad' serotonin can impact HPTA-neuroendocrine function?
Btw, in Figure 4 of this same paper they interestingly recommend consdering Lamictal as one of the things for people with TRD/SSRI non-response.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033019/
Look what I found. Earlier in the thread you said that things would just downregulate with excess 5-HT right?
But this paper claims:
"Although description of the functional attributes of the serotonin polymorphism have been contradictory (Karg et al., 2011), clinical data would prompt us to suspect that the short allele is associated with an inability of the serotonin transporter to cope with excess synaptic 5-HT in the somatodendritic raphe area but this statement remains speculative."
So the *short* serotonin transporter supposedly has trouble with high 5-HT (though they admit its contradictory)
"The expected compensation of autoreceptor down-modulation to enhanced peri-raphe 5-HT is overwhelmed by the magnitude of agonism during “flooding” and putatively exceeds the capacity of the autoreceptor to sufficiently “down-modulate” (Blier et al., 1998) (Figure (Figure3),3), a contention supported by 5-HT1A irreversible KO rodent studies described below (see Bipolar Versus Unipolar Depression: Data from Animal Models)."
This paper is in reference to SSRI non response. But if MDMA releases tons of serotonin, could a similar thing happen with the short serotonin allele?
..And then of course presumably excess 'bad' serotonin can impact HPTA-neuroendocrine function?
Btw, in Figure 4 of this same paper they interestingly recommend consdering Lamictal as one of the things for people with TRD/SSRI non-response.
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