Scientific Spotlight: Study Shows Low Serotonin Levels are NOT Associated with Depression
But that doesn't mean that anti-depressants don't work
A few weeks ago a study came out which made the news circuit. It examined the relationship between serotonin and depression and found that low levels of serotonin are not associated depression. It has become one of the most widely shared medical articles. A quick review of headlines such as “Did we all believe a myth about depression?” or “The chemical imbalance theory of depression is dead…” show how easy it is to make correlations and conclusions that aren’t accurate. These sensationalized headlines don’t represent an accurate portrayal of the science and demonstrates how people try to oversimplify complex issues. When this article came out, I began getting questions from clients and family members such as “Does this mean antidepressants don’t work?” and “Does this mean that depression isn’t caused by a chemical imbalance?” Since these are important questions, I thought it would be helpful to share the science with readers of MTU as well.
Do results from this study indicate that anti-depressants don’t work? The short answer is no. The study didn’t actually test this question, however it is easy to make that assumption.
What did the study examine and find?
Okay, the fact that the study was published in Molecular Psychiatry is a sign it’s going to be a bit complicated. However in reality, it isn’t as off putting as it may initially seem. The study conducted a systematic review and what is called a “meta analysis” of existing literature to address this question. The first important thing to understand is no new or groundbreaking information emerges from a study of this nature. There are no new participants or data collection in a meta analysis. Rather these types of studies examine the existing literature for consistency across studies that were conducted in the past. Meta analyses are important because sometimes we see conflicting information across different studies which makes it difficult to conclude which studies reflect accurate information. When we find consistency (or reliability) it gives us more confidence in the findings. So let’s talk about what question the study actually asked and what it found.
The main objective of the study was to determine whether low levels of serotonin (a chemical in the brain) have a significant relationship with depression. The reason this question is being asked is because in the 1960s a theory emerged that suggested low levels of serotonin played a pivotal role in depression. However, several studies conducted over the past decades don’t actually find evidence for this theory. The main finding of the study found that the serotonin theory is not supported by research evidence. That may be surprising to you as the news headlines illustrate. It’s important to note that the study only examined this question in relation to Major Depressive Disorder and didn’t include studies that looked at specific types of depression (e.g., bipolar depression, postpartum depression). Also, it’s important to note that serotonin is just one of many chemicals in our complex brain chemistry.
How was the relationship between serotonin levels and depression examined in the current study? They looked at several studies that tested this question in unique ways by asking:
Are there significant differences between individuals with depression and those with no symptoms of depression with regard to the following: Serotonin levels, serotonin receptors, the way serotonin is transported in the brain?
The study found that the answer is no. They found no evidence in the literature of significant differences between groups on serotonin levels, receptors, or proteins associated with transporting serotonin. This gets at associations or relationships, and less about causation. As you can imagine, the findings from these studies were probably unexpected.
If we intentionally lower or deplete serotonin levels, will people exhibit depression? Again, the study found that the answer is no. You might be wondering, how can serotonin levels be reduced? Participants receive a drink that temporarily depletes tryptophan and consequently serotonin. If there is a direct and strong causal relationship between serotonin and depression we would expect individuals to report increased depressive symptoms as serotonin levels decrease. This was not found to be the case across multiple studies. These findings provide further support that low serotonin levels do not directly cause depression.
Overall, the evidence doesn’t support a significant relationship between serotonin and depression, at least directly. The authors conclude that stating depression is due to a “chemical imbalance” of serotonin isn’t an accurate statement.
So what causes depression?
Well, we don’t exactly know. There is no silver bullet, but it most likely is caused by a combination of factors. As with many issues, it usually comes down to a combination of individual and environmental (or situational) influences.
Are antidepressants helpful in treating depression?
The short answer is yes. Several studies have addressed this question and have found that antidepressants do improve depressive symptoms, however we don’t know exactly why. It makes sense that the efficacy of antidepressants would arise in the context of the above study since the serotonin theory influenced the development of SSRI (Selective Serotonin Reuptake Inhibitors) medication to treat depression. Currently, the most popular medications prescribed for the treatment of depression are as follows:
Fluoxetine (Prozac)
Escitalopram (Lexapro)
Citalopram (Celexa)
Paroxetine (Paxil, Pexeva)
Sertraline (Zoloft)
Here is what we do know about antidepressants:
SSRIs that focus on serotonin levels in the brain have been helpful in treating depression (as well as other conditions such as anxiety). There are multiple trials that have examined this and millions of users who have taken SSRIs have had success. There are also other medications that successfully treat depression that work on other chemicals in the brains besides serotonin such as Wellbutrin, Effexor, etc. These medications focus on dopamine and norepinephrine, not serotonin. It is also helpful to note that SSRIs don’t work the same for everyone and some individuals experience side effects which preclude them from taking them.
More importantly, the most optimal and efficacious treatment of depression involves other treatment modalities in addition to medication such as therapy and lifestyle habits (e.g., exercise, mindfulness practice). It really is important to incorporate these into a treatment plan.
Depression can improve without the use of medication. For instance several therapies such as cognitive behavioral therapy, mindfulness-based cognitive therapy, and interpersonal therapy have been shown to significantly improve mood and reduce depressive symptoms compared to control conditions.
Overall, treating depression is not a one size fits all approach. If you have questions or concerns about medications you are currently taking or are considering taking, the most helpful course of action is to talk to your physician.
Finally, one of the reasons I started writing mental tune-ups was to make the scientific literature more user friendly, approachable, and without sensationalized headlines. This prompted me to develop this “Scientific Spotlight” post. When new and relevant studies emerge, I will discuss the study and provide insights and present the findings in a more user friendly style.