This month, the media carried reports of a scientific study that challenged the notion of serotonin’s role in depression, which in turn casts doubts about the use of SSRI antidepressants to treat the illness.
The similar wording of these reports suggests that the reporters were engaging in a copy-and-paste of the same press release. Let’s go beyond the press release ...
First, the monoamine hypothesis ...
Serotonin is a monoamine class of neurotransmitter. Monoamine refers to the neurotransmitter’s chemical composition. Two other monoamines (falling into a subclass called catecholamines) include dopamine and norepinephrine.
As we know, neurotransmitters act as chemical signals between neurons. Neurons, in turn, organize into complex pathways that prompt specific thoughts and emotions and reactions. Serotonin is strongly linked to mood, and - make no mistake about this - no study is about to unseat that notion.
Meanwhile, dopamine is associated with pleasure and reward and norepinephrine with alertness. These are vast oversimplifications, but let’s not make this too complicated.
Enter the monoamine hypothesis of depression, which is seen as the depletion of these three neurotransmitters in the central nervous system. The implication is that antidepressants will restore the “chemical imbalance,” and here the problem starts.
An imperfect hypothesis, at best ...
In a review article published in 2000, leading depression authority Robert Hirschfeld of the University of Texas (Galveston) noted that the monoamine hypothesis “does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown.”
He also noted that some meds that enhance serotonin and norepinephrine function have no effect at alleviating depression.
It’s not that the hypothesis is wrong, per se, it’s just that it has a lot of major holes in it.
Enter the dreaded Zoloft commercial ...
Anyone with access to a TV back in the early 2000s has seen the ad with the sad neuron with the “chemical imbalance” that becomes happy once Zoloft “corrects this imbalance.”
Unfortunately, doctors who should know better still tell their patients almost exactly the same story when prescribing SSRI medications to their patients.
SSRIs (serotonin-enhancing drugs) came on the scene in the late 80s-early 90s. Early findings indicated something like an 80 percent success rate for treating depression, and even today in scholarly articles you see this figure bandied about.
Later findings scaled the success rate down to about 50 percent, and a closer look revealed that these so-called successes typically involved only about a 50 percent improvement in symptoms. So - in actuality, contrary to what the drug companies want you to believe - only a minority of people taking antidepressants display the kind of improvement you see in the Zoloft ad.
Add to that the well-known “poop-out” rate, plus side effects, plus the risk of mania and cycling, and it’s clear that rather than correcting chemical imbalances, these meds - for many people - are making chemical imbalances only worse.
That is, assuming there is a such thing as a chemical imbalance, in the first place.
The chemical imbalance myth ...
In a blog piece I posted earlier this year, I go into considerable detail how the complexities of the brain render the idea of chemical imbalance palpably absurd. These same complexities also strongly challenge our classic view of “depression.”
Yes, we get “depressed.” But what is it? Where did it come from? How can we address what is wrong with us? Short answer: The more we know, the less we know. But if we want to get to the bottom of all of this, perhaps we need to discard the notion of depression entirely, together with the idea of a quick chemical fix.
Instead, let’s figure out what is really going on. Modern brain science is yielding amazing discoveries, but all this is going to take time.
Animal studies ...
For decades, experiments on lab rats and mice have been at the forefront of research into what makes humans think and behave as they do. Part of this has to do with torturing the animals into a state of “learned helplessness,” which parallels our human concept of depression.
Another part of this has to do with genetically engineering “knock-out” mice. This brings us to our study in question ...
The study ...
In an article in the Aug 4 ACS Chemical Neuroscience, researchers from the Wayne State University School of Medicine report how they bred mice to lack a certain gene responsible for producing tryptophan hydroxylase, an amino acid responsible for synthesizing serotonin.
These serotonin-deficient mice were then subjected to a battery of standard tests, including the “forced swim test” and the “tail suspension test.” Surprisingly, their reactions were similar to the control mice in the study. Thus, the serotonin-deprived bunch put up the same kind of fight as their normal counterparts.
In other words, these mice were not “depressed.”
On the other hand, you wouldn't want one for a pet, either. What the researchers did observe based on previous studies is that these mice exhibited marked compulsivity and impulsivity and aggression. In other words, the lack of serotonin is clearly demonstrating a pronounced behavioral effect. These mice are clearly in bad “mood,” only the mood doesn’t look like depression.
Before you jump to conclusions ...
Mice are not human beings. They cannot tell us what they are thinking, whether they are going through an existentialist crisis or sulking over a social snub or fretting about what the future holds in store or not. We can learn a lot from watching their behavior, but not everything.
Moreover, the authors themselves raised the suggestion that there may be a difference between the type of total serotonin depletion that these study mice endured and a partial serotonin depletion.
Here, we only have to look at studies on humans, carried out in the late 90s. Here, the study subjects were given a drink that had the effect of depleting tryptophan in the brain, which in turn reduced serotonin synthesis. Those in recovery from depression tended to experience an instant relapse. “Healthy” subjects also tended to experience a worsening in mood.
In other words, we have evidence for serotonin being a major player in depression, but we lack major clues concerning what it is doing on the field or its role in the overall game or who the other players are.
What our study actually supports ...
The immense complexity of the brain defies our quest for easy answers, particularly with regard to cause-and-effect or problem-and-solution. An “antidepressant” is no more a remedy for “depression” than a boost in serotonin is an antidote for a “serotonin deficiency.”
Or - to totally confuse the issue - it may be the case, sometimes.
Clear as mud, right? Good. That's something we can all agree on.
Published On: September 29, 2014