peer-reviewed-myopia t1_j8xwm8t wrote on February 17, 2023 at 7:04 PM

I don't understand the value of this research. Depression has been known to correlate with memory dysfunction and decreased hippocampal volume. 5-HT4 (serotonin 4) receptors have been known to be involved with memory, and the structural plasticity effects within the hippocampus.

However, compared to other serotonin receptors, the function of 5-HT4 throughout the brain and periphery is diverse and complex — which makes sense when considering how relatively large / complicated the gene encoding 5-HT4 is, and how little is known about the regulation of its transcription.

There is strong evidence regarding the involvement of 5-HT4 in depression, but imaging that quantifies global reductions is completely insufficient. Humans show different responses in 5-HT4R expression in different brain regions. SSRIs have been shown to decrease global 5-HT4 binding. Depressed suicide victims show increased 5-HT4 receptor binding in the caudate nucleus and frontal cortex.

This study has zero value in paving the way for new drugs.

Morthra t1_j8z1ry0 wrote on February 17, 2023 at 11:44 PM

But wasn't there a recent study that showed SSRIs are no more effective than placebo?

[deleted] t1_j8zeqjt wrote on February 18, 2023 at 1:25 AM

[deleted]

InTheEndEntropyWins t1_j91mlec wrote on February 18, 2023 at 3:29 PM

There was a study saying that there is no good evidence that low serotonin levels being related to depression.

SSRI's do work for some people but they aren't fixing any underlying chemical imbalance in the brain. Think of them as a painkiller, they help with the symptoms but aren't fixing some underlying issue.

redvodkandpinkgin t1_j912bed wrote on February 18, 2023 at 12:34 PM

I don't know the study you reference, but SSRIs and SNRIs were shown to improve depression over placebos countless times for a long time now. It's no miracle, mind you, but it still works at least better than nothing

Morthra t1_j917j3f wrote on February 18, 2023 at 1:27 PM

I found it. It was this paper. For 85% of people SSRIs are no better than placebo.

redvodkandpinkgin t1_j91kyp0 wrote on February 18, 2023 at 3:17 PM

That study defends my point though. It's right in the abstract

>Results The random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5% v 9.6%) and less likely to have a Minimal response (12.2.% v 21.5%).

Depression is an insanely difficult to treat disorder. There is no one drug that cures it or even makes it manageable for everyone; hell, they din't help me a whole lot with it. But the medicine works for some people. More importantly, it seems to help more those with a more severe depression. It's no miracle, but it can help some together with therapy.

We still don't have a good drug for it, sure, but it's not like a placebo, it does help.