<p>It's all about the receptors, really.  There are 7 families of serotonin receptors that perform different functions within the brain, and according to <a href="http://en.wikipedia.org/wiki/5-HT_receptor">Wikipedia</a> 14 different subtypes have been discovered. </p>

<p>The article assumes that a blanket level of serotonin would be sufficient to "perk" up the brain, wherein it is much more complicated.  Serotonin serves to modulate the level of excitation or inhibition depending on the circumstances.  Most of the "effect" from today's antidepressants is related to modulating projections from the dorsal raphe in the brainstem to dopaminergic neurons in the frontal cortex, but some of the serotonergic neurons in the basal ganglia can be hyperactive in situations where there is mild psychosis.  So, depending on the etiology of the depression, suppressing those neurons local to that portion of the anatomy can actually be helpful.</p>

<p>So, it's less to do with the transmitter that is being discussed, and everything to do with which subtypes of receptors are being agonized or antagonized.  While we have learned a tremendous amount about the relationships between neurotransmitters at different nuclei, we still have a lifetime or more of research to go.  </p>

CC BY-SA 3.0
2013-09-04T04:06:38.923Z
2013-09-04T04:06:38.923Z
Chuck Sherrington
<p>I suppose at face value, the answer to the question "Is serotonin <em>linked</em> to depression?" would 'yes'.  However, if the question was "Is Major Depressive Disorder or Dysthimia the result of deficits in serotonergic signaling?" the answer becomes much less black-and-white.  First, to piggyback on Chuck's response, it is very important to consider 5-HT (serotonin) receptor subtypes, since different subtypes can play significantly different roles in modulating a massive amount of cognitive and physiological processes.  These range from autonomic functions such as pupil dilation, appetite, sexual arousal etc..., to high level cognitive and social behaviors/functions such as aggression, mood, impulsiveness, addiction etc.  It is a gross oversimplification to think in terms of "more" or "less" serotonin being the grand underlying factor in depression.  Certainly, like most every aspect of a biological system, there are going to be consequences when there are critical deficits or excessive amounts of neuromodulatory chemicals such as serotonin, but there are many other factors that clinicians and researchers have found to be important relative to depression.</p>

<p>Some of these are not surprising and pretty intuitive, such as dysregulation of other neurotransmitter systems, particularly monoamines such as dopamine, norepinephrine, and epinephrine as these chemicals also modulate mood and arousal.</p>

<p>Recent research has also shown that antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs), to name a few, owe their therapeutic qualities, at least secondarily, to increased neurogenesis in hippocampus which also explains the improvement in general cognitive function many depressed individuals report when successfully treated. (1)  Some researchers argue that this is actually the primary mechanism underlying the attenuation of depressive symptoms when using these pharmacological therapies.  </p>

<p>Other connections have been made to increased inflammation (2) as an important factor in depression.  Depressive symptoms have actually been shown to be <em>caused</em> by long term interactions from adipose tissue (a major source of inflammation) on neural regulatory systems.</p>

<p>So, I'll wrap this up by saying that yes, serotonin is <em>linked</em> to depression.  The link is still just that, a link.  For a variety of historical reasons, relating serotonin to depression somehow comes off as a hot topic of debate, but this is because of gross oversimplifications that are provided to the public by the media, pharmaceutical companies, clinicians and even the researchers studying depression and the neurophysiology behind it.  </p>

<ol>
<li><p>Castrén E (March 2005). "Is mood chemistry?". Nat Rev Neurosci. 6 (3): 241–6. doi:10.1038/nrn1629. PMID 15738959.</p></li>
<li><p>Shelton RC, Miller AH. Inflammation in depression: is adiposity a cause? Dialogues Clin Neurosci. 2011;13(1):41-53.</p></li>
</ol>

CC BY-SA 3.0
2013-09-10T16:05:58.100Z
This is good, but I wish someone could explain the subtype that is responsible for feeling blue. It seems SSRIs lift the whole range of subtypes, resulting in GI, sleeping and sexual side effects. If one can't eat, can't sleep, is anorgasmic, has headaches... those sound like very good reasons to be depressed, ironically.
Randy
CC BY-SA 3.0
2013-09-10T13:01:50.557Z
2013-09-10T13:01:50.557Z
aMarbledNine
<p>Now I didn't read the whole discussion beforehand, just skimmed through it. 
Maps.org /Yale Uni is doing quite a bit interesting research on the topic, having better results than any existing antidepressants could dream of. Psilocybin/ LSD/ DMT/ MDMA could be far out to read up on, but psychedelics/ empathogens may be the future answer to a part of the question.</p>

<p>If you check out the Cochrane library on LSD, they also show a significant effect on the global brain communication after intake, which may be beneficial to reset the "loops" that the depressed/ dysfunctional/ addictive brain is in. </p>

<p>I also like the "Deep Rest" (ref: Jim Carrey?) interpretation of depression. It comes to tell your body to take some time off, de-stress, process known or unknown traumas and to find who you are and your purpose here on earth -whatever that may be. Most people don't have time to get to know themselves today, so they rather work long hours to fit into the majority of well adjusted misfits. </p>

<p>For me, I get energy from learning new things at my own pace, finding new subjects of digging into, sharing and discussing knowledge and philosophy, helping people where I can ++. Many places pay people who doesn't even truly care, or care for the wrong reasons, to do these things. But now we're over to worldbuilding. </p>

<p>Follow the money, and you are on the right path to the wrong solution. </p>

CC BY-SA 4.0
2018-05-21T23:21:25.550Z
Welcome. How does this answer the question? We encourage specific and scientifically sound answers. References, sources and an explicit answer to the question can improve your post. As of now, it seems more like an unsubstantiated opinion. -1
AliceD
CC BY-SA 4.0
2018-05-21T21:23:11.043Z
2018-05-21T21:23:11.043Z
user13005
<p>Some highlights from the article &quot;<a href="https://web.archive.org/web/20110816122449/http://www.thedailybeast.com/newsweek/2010/01/28/the-depressing-news-about-antidepressants.html" rel="noreferrer">The Depressing News about Anti-Depressants</a>&quot;:</p>
<blockquote>
<p>ever since a seminal study in 1998, whose findings were reinforced by landmark research in The Journal of the American Medical Association last month, that evidence has come with a big asterisk. Yes, the drugs are effective, in that they lift depression in most patients. But that benefit is hardly more than what patients get when they, unknowingly and as part of a study, take a dummy pill—a placebo. As more and more scientists who study depression and the drugs that treat it are concluding, that suggests that <strong>antidepressants are basically expensive Tic Tacs.</strong></p>
<p>One team of researchers wondered if antidepressants were &quot;a triumph of marketing over science.&quot; Even defenders of antidepressants agreed that the drugs have &quot;relatively small&quot; effects. &quot;Many have long been unimpressed by the magnitude of the differences observed between treatments and controls,&quot; psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote—&quot;what some of our colleagues refer to as 'the dirty little secret.' &quot;In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.</p>
<p>But if experts know that antidepressants are hardly better than placebos, few patients or doctors do. Some doctors have changed their prescribing habits, says Kirsch, but more &quot;reacted with anger and incredulity.&quot;</p>
<p>Doctors see with their own eyes, and feel with their hearts, that the drugs lift the black cloud from many of their depressed patients. But since doctors are not exactly in the habit of prescribing dummy pills, they have no experience comparing how their patients do on them, and therefore never see that a placebo would be almost as effective as a $4 pill. &quot;When they prescribe a treatment and it works,&quot; says Kirsch, &quot;their natural tendency is to attribute the cure to the treatment.&quot; Hence the widespread &quot;antidepressants work&quot; refrain that persists to this day.</p>
<p>Right about here, people scowl and ask how anti-depressants—especially those that raise the brain's levels of serotonin—can possibly have no direct chemical effect on the brain. Surely raising serotonin levels should right the synapses' &quot;chemical imbalance&quot; and lift depression. Unfortunately, the serotonin-deficit theory of depression is built on a foundation of tissue paper. How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression. Iproniazid increases brain levels of serotonin and norepinephrine. Ergo, low levels of those neurotransmitters must cause depression. More than 50 years on, the presumed effectiveness of antidepressants that act this way remains the chief support for the chemical-imbalance theory of depression. Absent that effectiveness, the theory hasn't a leg to stand on. Direct evidence doesn't exist. Lowering people's serotonin levels does not change their mood. And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. <strong>&quot;If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,&quot; says Kirsch, &quot;it's hard to imagine how the benefits can be due to their chemical activity.&quot;</strong></p>
</blockquote>
<p>Is this article true?  What evidence is there that serotonin is linked to depression?</p>

CC BY-SA 3.0
2017-12-18T15:52:40.710Z
Related question about tianeptine https://cogsci.stackexchange.com/questions/18685/is-tianeptine-addictive
got trolled too much this week
<neuroscience><abnormal-psychology><depression><neuro-transmitters>
Is serotonin conclusively linked to depression?
Randy
# Is serotonin conclusively linked to depression?

(Asked by: username_0 on 2013-09-04)

Some highlights from the article "[The Depressing News about Anti-Depressants](https://web.archive.org/web/20110816122449/http://www.thedailybeast.com/newsweek/2010/01/28/the-depressing-news-about-antidepressants.html)":

> ever since a seminal study in 1998, whose findings were reinforced by landmark research in The Journal of the American Medical Association last month, that evidence has come with a big asterisk. Yes, the drugs are effective, in that they lift depression in most patients. But that benefit is hardly more than what patients get when they, unknowingly and as part of a study, take a dummy pill—a placebo. As more and more scientists who study depression and the drugs that treat it are concluding, that suggests that **antidepressants are basically expensive Tic Tacs.**
>
> One team of researchers wondered if antidepressants were "a triumph of marketing over science." Even defenders of antidepressants agreed that the drugs have "relatively small" effects. "Many have long been unimpressed by the magnitude of the differences observed between treatments and controls," psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote—"what some of our colleagues refer to as 'the dirty little secret.' "In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.
>
> But if experts know that antidepressants are hardly better than placebos, few patients or doctors do. Some doctors have changed their prescribing habits, says Kirsch, but more "reacted with anger and incredulity."
>
> Doctors see with their own eyes, and feel with their hearts, that the drugs lift the black cloud from many of their depressed patients. But since doctors are not exactly in the habit of prescribing dummy pills, they have no experience comparing how their patients do on them, and therefore never see that a placebo would be almost as effective as a $4 pill. "When they prescribe a treatment and it works," says Kirsch, "their natural tendency is to attribute the cure to the treatment." Hence the widespread "antidepressants work" refrain that persists to this day.
>
> Right about here, people scowl and ask how anti-depressants—especially those that raise the brain's levels of serotonin—can possibly have no direct chemical effect on the brain. Surely raising serotonin levels should right the synapses' "chemical imbalance" and lift depression. Unfortunately, the serotonin-deficit theory of depression is built on a foundation of tissue paper. How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression. Iproniazid increases brain levels of serotonin and norepinephrine. Ergo, low levels of those neurotransmitters must cause depression. More than 50 years on, the presumed effectiveness of antidepressants that act this way remains the chief support for the chemical-imbalance theory of depression. Absent that effectiveness, the theory hasn't a leg to stand on. Direct evidence doesn't exist. Lowering people's serotonin levels does not change their mood. And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. **"If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it," says Kirsch, "it's hard to imagine how the benefits can be due to their chemical activity."**

Is this article true? What evidence is there that serotonin is linked to depression?

**Tags:** neuroscience, abnormal-psychology, depression, neuro-transmitters

> **Comments:**
> **username_1**: Related question about tianeptine https://cogsci.stackexchange.com/questions/18685/is-tianeptine-addictive  

---

## 3 answers

### Answer by username_2 on 2013-09-04. Score: 14

It's all about the receptors, really. There are 7 families of serotonin receptors that perform different functions within the brain, and according to [Wikipedia](http://en.wikipedia.org/wiki/5-HT_receptor) 14 different subtypes have been discovered.

The article assumes that a blanket level of serotonin would be sufficient to "perk" up the brain, wherein it is much more complicated. Serotonin serves to modulate the level of excitation or inhibition depending on the circumstances. Most of the "effect" from today's antidepressants is related to modulating projections from the dorsal raphe in the brainstem to dopaminergic neurons in the frontal cortex, but some of the serotonergic neurons in the basal ganglia can be hyperactive in situations where there is mild psychosis. So, depending on the etiology of the depression, suppressing those neurons local to that portion of the anatomy can actually be helpful.

So, it's less to do with the transmitter that is being discussed, and everything to do with which subtypes of receptors are being agonized or antagonized. While we have learned a tremendous amount about the relationships between neurotransmitters at different nuclei, we still have a lifetime or more of research to go.


---

### Answer by username_3 on 2013-09-10. Score: 10

I suppose at face value, the answer to the question "Is serotonin *linked* to depression?" would 'yes'. However, if the question was "Is Major Depressive Disorder or Dysthimia the result of deficits in serotonergic signaling?" the answer becomes much less black-and-white. First, to piggyback on Chuck's response, it is very important to consider 5-HT (serotonin) receptor subtypes, since different subtypes can play significantly different roles in modulating a massive amount of cognitive and physiological processes. These range from autonomic functions such as pupil dilation, appetite, sexual arousal etc..., to high level cognitive and social behaviors/functions such as aggression, mood, impulsiveness, addiction etc. It is a gross oversimplification to think in terms of "more" or "less" serotonin being the grand underlying factor in depression. Certainly, like most every aspect of a biological system, there are going to be consequences when there are critical deficits or excessive amounts of neuromodulatory chemicals such as serotonin, but there are many other factors that clinicians and researchers have found to be important relative to depression.

Some of these are not surprising and pretty intuitive, such as dysregulation of other neurotransmitter systems, particularly monoamines such as dopamine, norepinephrine, and epinephrine as these chemicals also modulate mood and arousal.

Recent research has also shown that antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs), to name a few, owe their therapeutic qualities, at least secondarily, to increased neurogenesis in hippocampus which also explains the improvement in general cognitive function many depressed individuals report when successfully treated. (1) Some researchers argue that this is actually the primary mechanism underlying the attenuation of depressive symptoms when using these pharmacological therapies.

Other connections have been made to increased inflammation (2) as an important factor in depression. Depressive symptoms have actually been shown to be *caused* by long term interactions from adipose tissue (a major source of inflammation) on neural regulatory systems.

So, I'll wrap this up by saying that yes, serotonin is *linked* to depression. The link is still just that, a link. For a variety of historical reasons, relating serotonin to depression somehow comes off as a hot topic of debate, but this is because of gross oversimplifications that are provided to the public by the media, pharmaceutical companies, clinicians and even the researchers studying depression and the neurophysiology behind it.

1. Castrén E (March 2005). "Is mood chemistry?". Nat Rev Neurosci. 6 (3): 241–6. doi:10.1038/nrn1629. PMID 15738959.
2. Shelton RC, Miller AH. Inflammation in depression: is adiposity a cause? Dialogues Clin Neurosci. 2011;13(1):41-53.

> **Comments:**
> **username_0**: This is good, but I wish someone could explain the subtype that is responsible for feeling blue. It seems SSRIs lift the whole range of subtypes, resulting in GI, sleeping and sexual side effects. If one can't eat, can't sleep, is anorgasmic, has headaches... those sound like very good reasons to be depressed, ironically.  

---

### Answer by username_4 on 2018-05-21. Score: -2

Now I didn't read the whole discussion beforehand, just skimmed through it.
Maps.org /Yale Uni is doing quite a bit interesting research on the topic, having better results than any existing antidepressants could dream of. Psilocybin/ LSD/ DMT/ MDMA could be far out to read up on, but psychedelics/ empathogens may be the future answer to a part of the question.

If you check out the Cochrane library on LSD, they also show a significant effect on the global brain communication after intake, which may be beneficial to reset the "loops" that the depressed/ dysfunctional/ addictive brain is in.

I also like the "Deep Rest" (ref: Jim Carrey?) interpretation of depression. It comes to tell your body to take some time off, de-stress, process known or unknown traumas and to find who you are and your purpose here on earth -whatever that may be. Most people don't have time to get to know themselves today, so they rather work long hours to fit into the majority of well adjusted misfits.

For me, I get energy from learning new things at my own pace, finding new subjects of digging into, sharing and discussing knowledge and philosophy, helping people where I can ++. Many places pay people who doesn't even truly care, or care for the wrong reasons, to do these things. But now we're over to worldbuilding.

Follow the money, and you are on the right path to the wrong solution.

> **Comments:**
> **username_5**: Welcome. How does this answer the question? We encourage specific and scientifically sound answers. References, sources and an explicit answer to the question can improve your post. As of now, it seems more like an unsubstantiated opinion. -1  

---

