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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by TriedEveryMedication on July 29, 2022, at 23:24:43
Large meta-analysis of 17 studies with over 150,000 subjects:
https://www.nature.com/articles/s41380-022-01661-0
"The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations."
"Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers."
Posted by PeterMartin on July 30, 2022, at 8:36:32
In reply to serotonin theory of depression torpedoed, posted by TriedEveryMedication on July 29, 2022, at 23:24:43
Saw this on media like "The Hill". Meta-analysis is all they did? Eh..
In the time of "antivaxers", willing to go as far as not allowing their dogs & cats to get shots, this seems more like click-bait for those who want to blame "big pharma" for some foxnews conspiracy theory.
I've taken meds that work on Serotonin for decades - they help me. Putting out a paper w/ a headline like that will convince many who could be helped by medication (perhaps life savingly so) to continue suffering.
Posted by linkadge on July 30, 2022, at 8:42:06
In reply to serotonin theory of depression torpedoed, posted by TriedEveryMedication on July 29, 2022, at 23:24:43
This is not really news. Many psychiatrists and researchers have knows this for some time now.
Contrary to popular believe, SSRIs don't just raise serotonin:
- influence stress hormones and other hormones
- affect gene expression via HDAC inhibition
- affect g-proteins
- affect the trk-b receptor (binds to BDNF)
- affect glutamate and gaba neurotransmission
- post the level of P11 protein
- much much moreAlso, just because depression isn't due to low serotonin, doesn't mean that raising serotonin isn't somehow therapeutic. The same can be said for thyroid. Even in bipolar patients with 'normal' thyroid, raising it to supertheraputic levels can alleviate symptoms.
Also, the research does not bear out the possibility that some other aspect of the serotonergic system is dysfunctional. We just don't know at this point.
What really pisses me off, however, are the news articles that are broadcasting "according to recent study, there is no evidence of a chemical imbalance in depression". This is false. There are decades of research showing many biochemical abnormalities in depression. The problem is that there is no 'unified' theory. Not everybody's depression is the same. This of course, makes sense, because we are not dealing with a single gene or environmental background.
Finally, everything eventually becomes chemical. Childhood maltreatment, if it results in a mental illness, ultimately causes a 'chemical imbalance'. Also, virtually all effective treatments (medications or otherwise) can normalize some of the chemical imbalances seen in depression.
Linkadge
Posted by TriedEveryMedication on July 30, 2022, at 10:43:15
In reply to Re: serotonin theory of depression torpedoed, posted by PeterMartin on July 30, 2022, at 8:36:32
> Saw this on media like "The Hill". Meta-analysis is all they did? Eh..
>
> In the time of "antivaxers", willing to go as far as not allowing their dogs & cats to get shots, this seems more like click-bait for those who want to blame "big pharma" for some foxnews conspiracy theory.
>
> I've taken meds that work on Serotonin for decades - they help me. Putting out a paper w/ a headline like that will convince many who could be helped by medication (perhaps life savingly so) to continue suffering.Undoubtedly SSRIs/SNRIs/etc work for millions of people. It is quite possible they have some other mechanism of action aside from increasing serotonin that makes them efficacious, though.
Posted by Jay2112 on July 30, 2022, at 18:33:08
In reply to Re: serotonin theory of depression torpedoed, posted by linkadge on July 30, 2022, at 8:42:06
Just to add:
-It's not quite serotonin levels, as too much serotonin is also implicated in: social anxiety, GAD, suicidal impulses, and autism spectrum disorders. In those cases, it appears to be the downregulation that SSRI's cause that seems to tame the symptoms.
Not every med that affects serotonin levels is equal. The term "SSRI" really applies to only one current popular antidepressant...citalopram/escitalopram. Zoloft/sertraline is an SDRI (Serotonin/Dopamine re-uptake inhibitor) Prozac an SNRI with mild GABA enhancing properties. Paxil is an SNRI with anticholinergic properties..Luvox may be an SSRI, but has strong melatonin enhancing properties..
Jay
Posted by Phillipa on July 31, 2022, at 9:44:16
In reply to Re: serotonin theory of depression torpedoed, posted by PeterMartin on July 30, 2022, at 8:36:32
This was also posted on my RN medscape articles. I figured right away well if they don't work then maybe I should just stop taking them?
Posted by SLS on August 1, 2022, at 12:11:58
In reply to Re: serotonin theory of depression torpedoed » PeterMartin, posted by Phillipa on July 31, 2022, at 9:44:16
One thing to consider is the results of experiments conducted in the early 1990s manipulating amino acid intake in people with depression and those without depression. The people with depression had been stabilized and in remission on a serotonin reuptake inhibitor. In depressed people, a diet lacking tryptophan resulted in a relapse into depression. That same diet had no effect on healthy control subjects.
- Scott
Posted by linkadge on August 1, 2022, at 16:07:06
In reply to Re: serotonin theory of depression torpedoed, posted by Jay2112 on July 30, 2022, at 18:33:08
Here is food for thought...
In mice lacking the presynaptic serotonin autoreceptor, the anti-anxiety effects of SSRIs are absent.
The presynaptic receptor (when activated by serotonin) slows further serotonin release.
So, some of the mechanism for SSRIs may be a result of 'regulating' serotonin rather than simply raising it.
It is similar with methylphenidate. It can (believe it or not) reduce dopamine levels in ADHD models.
Linkadge
Posted by SLS on August 1, 2022, at 20:04:22
In reply to Re: serotonin theory of depression torpedoed, posted by linkadge on August 1, 2022, at 16:07:06
My doctor prefers to think of the amine "neurotransmitters" as actually being "neuromodulators". I don't understand it all, but perhaps the function of dopamine is to modulate the excitability of glutamate neurons. Likewise, serotonin might be a modulator of GABA neurons.
Of course, the brain is way too complicated for any one theory to explain it.
At least for now.
- Scott
Posted by Jay2112 on August 3, 2022, at 15:29:14
In reply to Re: serotonin theory of depression torpedoed, posted by linkadge on August 1, 2022, at 16:07:06
I really wonder why I have such a robust, positive reaction to risperidone, and older antipsychotics. It seems the blockade of serotonin helps me. To me, maybe because I am on the autism spectrum, there is a powerful anti-anxiety with haloperidol, risperidone. But, NOT the newer atypicals. Most of these have partial dopamine agonism, and that is horrid for my anxiety. Risperidone and lorazepam *kill* my anxiety, leaving me feeling slightly euphoric.
Hmmm...<shrug>...I dunno....
Jay
Posted by undopaminergic on August 5, 2022, at 5:40:44
In reply to Re: serotonin theory of depression torpedoed, posted by Jay2112 on August 3, 2022, at 15:29:14
> ... there is a powerful anti-anxiety with haloperidol, risperidone. But, NOT the newer atypicals. Most of these have partial dopamine agonism, ...
>I think among the anipsychotics, only aripiprazole, brexpiprazole, and carpiprazine are partial dopamine agonists.
-undopaminergic
This is the end of the thread.
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