Depression & Serotonin: The End of an Affair?

The idea that depression is caused by a chemical imbalance in the brain is not a new one and it’s not a rare one. I hear it daily from my clients, it’s what’s written in psychiatric textbooks, it’s the premise for most of the research done in the field.

But is it true? Latest data review indicates it might not be the case. As the review paper came out in Molecular Psychiatry about a month ago, almost a dozen of my colleagues shared it with me along with their very strong opinions. Many of them are upset and critical, feeling like this paper is attacking the very core of what they do, the most fundamental premise of contemporary psychiatry, the notion that psychological problems are in essence brain disorders. Another group of my colleagues feels vindicated, as they have kept their lingering doubts about biological basis of psychological disorders to themselves for years, fearing ostracism from the scientific community. Whereas it seems rather obvious to me that most of our psychological processes must have some kind of a correlate in brain activity, I am finding myself leaning towards the “vindicated” camp.

Even as a medical student, the hypothesis that serotonin deficiency causes depression seemed unsupported by evidence. In all its subsequent, more sophisticated iterations, it seemed equally unsupported. Of course, antidepressants do help some people, but just because an artificially induced change in serotonin availability improves the mood, doesn’t make the initial low mood a consequence of the lack of serotonin. When I was in high school we had logic as a mandatory subject and we learned about an informal logical fallacy called post hoc ergo propter hoc: just because A happened after B, doesn’t mean that B was caused by A. Otherwise, we could make a compelling case that anxiety is the deficiency of alcohol, because after a glass of wine you’re likely to be a little less anxious.  

This review looks at 17 previously published studies that show no evidence whatsoever that serotonin deficiency causes depression. Here’s the very last paragraph of the paper:

“This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.”

Anthony King, PhD from Ohio State University’s College of Medicine says: “The idea that depression is a chemical imbalance characterized by a deficit or a lower level of serotonin in the synapses is just not correct. It never was, and it’s not now.”Authors of the study in question argue that not only is this theory not supported by evidence, its insistent promotion by mental health professionals and its presence in the public discourse about mental health has detrimental effects:

“The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs.”

As a therapist who listen to people’s most intimate thoughts, I can confirm that this, indeed, is an issue. Once they conceptualize their difficulties as being biological, they stop seeking other ways of change. I am more often told that people want to find ways to “cope” with their depression, not get out of it, cure it. Once they see their depression as chemical in nature, people seem to give up on making fundamental changes in their lives. After all, how do you fight chemistry?

I have seen people’s lives changed by antidepressants, so I’m not arguing that they have no place in the treatment of depression. The question is how do they help and why if depression isn’t caused by the lack of serotonin. Another question is: why is it that this is the theory we hear about and why is it that we forget it’s only a theory? This paper, for me, is precisely what science is supposed to be – honest and clear and brave enough to question the dogma that’s never supposed to be found in science.

What’s the takeaway here?

Perhaps a return to the true spirit of science, the spirit of inquiry and openness, taking harder look at the evidence. Perhaps less biological reductionism and more emphasis on meaning-making processes and the transformation that psychotherapy can make. Perhaps even a step further: looking at individuals and what works for them and giving up on big theories and sweeping statements about something as complex as the human experience.