The Tautology of "Chemical Imbalance"
Even my biggest fans are often dismayed by my Szaszian skepticism of psychiatry. How can I be so at odds with the science? Of late, however, mainstream science journalism suddenly sounds Szaszian. Nature just published Moncrieff et al.’s major study, “The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence,” debunking the theory that depression is caused by serotonin deficiency. Science journalists seem convinced.
The original paper starts with critical background:
The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin… has been influential for decades, and provides an important justification for the use of antidepressants… Surveys suggest that 80% or more of the general public now believe it is established that depression is caused by a ‘chemical imbalance’ [15, 16]. Many general practitioners also subscribe to this view  and popular websites commonly cite the theory .
The paper goes on to conclude:
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. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.
The authors also step back and criticize the whole “chemical imbalance” view of depression. Hear this disapproving passage:
The chemical imbalance theory of depression is still put forward by professionals , and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades . The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities [15, 16], 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 [64,65,66]. 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 [67, 68].
Though I’d like to claim vindication, that wouldn’t be honest. “Does serotonin deficiency cause depression?” is a legitimate empirical question. A legitimate empirical question where I have zero independent knowledge.
The question, “Is depression caused by a chemical imbalance?,” in contrast, is a fake empirical question. Why? Because it is a thinly-veiled tautology. Depression is bad, right? We’re all made of chemicals, right? One scientific-sounding synonym for “bad” is “imbalanced,” right? So when psychiatrists say, “Depression is caused by a chemical imbalance,” it’s basically true by definition.
If this seems overly cynical, listen to what The Comprehensive Textbook of Psychiatry tells us about lithium:
Theories abound, but the explanation for lithium’s effectiveness remains unknown. Patients are often told it corrects a biochemical imbalance, and, for many, this explanation suffices. There is no evidence that bipolar mood disorder is a lithium deficiency state or that lithium works by correcting such a deficiency.
The upshot: No matter how powerfully Moncrieff et al. demonstrate the irrelevance of serotonin for depression, they can’t debunk the chemical imbalance “theory” because it’s not a theory at all.
What they could and should say, rather, is that presenting tautologies as scientific fact is charlatanism. Furthermore, a profession that widely tolerates such charlatanism merits broad skepticism - a skepticism Szasz wisely cultivated for his whole career. To be fair, you could object that charlatans are often skeptical of rival charlatans. But once you set aside unjustified deference for the psychiatric profession and judge Szasz’s arguments on their merits, you will not wish to so object.
P.S. Looking forward to meeting many of you in Princeton and NYC. Wish me luck on my comedy premiere; I’ll need it! Or do they say “Break a leg” in comedy?