A recently published an umbrella meta-analysis in the Journal of Molecular Psychiatry explored the ‘serotonin hypothesis’ of depression. Psychiatrist and lead researcher, Dr Mark Horowitz, describes the study in a recent interview. He also speaks to his own experience with depression and the withdrawals he faced while trying to stop anti-depressants.
The serotonin theory of depression characterises clinical depression as an imbalance in serotonin signalling. Serotonin, or 5-hydroxytryptamine, is a neurotransmitter that is ubiquitous in neuronal signalling throughout brain and gut. The theory serves the foundation of anti-depressant drugs, primarily serotonin reuptake inhibitors.
The study surveyed meta-analyses that tested specific aspects of the serotonin hypothesis. Overwhelmingly, studies spanning animal to human to clinical models do not have conclusive evidence that depression is related to either serotonin, its active metabolites, receptor regulation, or reuptake inhibition.
Dr Horowitz takes a stance that this theory of chemical imbalance and over-fixation on the neurotransmitter, serotonin, has stood as a ‘categorical error’ in psychiatry. We are looking at the wrong level of analysis to understand psychiatric disease.
This categorical error is akin to using a microscope to try to find the moon. The categorical error of the serotonin theory of depression and the subsequent terminology of ‘chemical imbalances’ is a greater symptom of mistaking the machinery of things for the being of things.
So why has the categorical error persisted?
1. Abstraction offers a sense of control
Language offers an abstraction of human experience. Scientific terms such as ‘chemical imbalance’, or even ‘depression’ itself, can offer a simplification and subtle escape from the rawness of experience.
Consider our modern discourse with phrases like:
“They are so toxic!”
“My serotonin is so low!”
“I need to go on a dopamine fast!”
The above sentences hijack psychological and scientific terms to express relatively simple feelings and behaviours.
“They are so toxic”, really means: “I feel hurt/confused/distrustful of someone based on a recent encounter”.
“My serotonin is so low!” is a fancy way of saying: “I feel sad”.
And of course, the over-fixation of dopamine in our modern discourse can be simplified into:
“I feel distracted and over-stimulated by short term pleasures.”
The serotonin hypothesis poses depression as problem that may be solved. The abstraction of human experience and feeling frees the individual of the personal circumstance and offers a departure from the rawness of reality into a scientific, solvable equations.
The non-pharmacological (some may say placebo) effects of SSRIs are greatly increased because the framing of the problem creates an expectancy bias. The narrative that suffering is due to a lack of chemicals, and then offering the said lack in the form of the pill, can help attribute any felt effects of the pill to ‘solving’ the perceived problem. Even if these effects are phenomenologically insignificant or simply sedative.
Chemical-fying a complex state of being such as depression is completely understandable and may even be helpful in the short-term. Reclaiming control, even through abstraction, can be an important step of recovery. However, in the long run, as a theoretical foundation, the serotonin hypothesis limits the progress and holistic understanding of depression.
2. Numbness or Processing?
Psychiatric drugs are super effective sedatives. The gold-standard anti-psychotics are also viable sedative drugs used in situations when patients may be aggressive or require immobilisation.
For example, in extreme schizophrenia we don’t have the understanding or resources to manage the intensity of such affect and behaviour. In such cases, we accept that chronic sedation may be the best option. But this requires some humility with respects to our understanding of the disease and restraint from generalising sedation to some psychopharmacological unified theory of schizophrenia.
The same can be said about anti-depressants. Subjectively, many users of such drugs report a blunting of affect. This may be helpful when the explosiveness of affect interferes with basic activities that we rely on for our own regulation, such as sleep. However, chronically, antidepressants ameliorate the lowest of lows but so too blunt the highest of highs.
The depth of depression may be a natural shutting down after waves of intense emotion or confronting psychological patterns that are too much to bear. It is not surprising that for some, the depths of depression have also been some of the most pivotal periods where major change and a revolution of the self has taken place. Depression may be the transition point of unconscious processing moving to the conscious space that may take a long time and multifactored care to facilitate.
The popularisation of the ‘chemical imbalance’ view of depression and the subsequent reliance on anti-depressant medication, may be a symptom of a medical system that is excellent at acute care. Numbing the problem in the timeframe of days and week looks a lot like wellness compared to the tumult of processing of waves of emotion, old patterns of behaviour thought, re-evaluating relationship that are no longer viable, or even resurfacing past traumas.
3. Depression as an identity
As we enter a society that is a lot more accepting and understanding of psychiatric conditions, we also face the dangers of forming an identity derived from our diagnostic status.
The ‘serotonin hypothesis’, has been revolutionary because it has cushioned the space between depression and blame. The radical self-agency of Western culture has, in the past, regarded negative emotions as a fault of self. The serotonin hypothesis offers a discourse in which we understand our state, feelings, and psychological frame, as the effect of cascading environments including our genetic makeup, neurobiology and our outer environment.
This revolution has reverberated throughout different psychiatric diagnoses, perhaps most predominantly in recent years, within Attention Deficit and Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). However, the dark side of a diagnostic dialogue is the creation of a pathological identity. The moment we put a name to our human experience, we add a layer of limitation.
The first step of psychiatric diagnosis is the freedom from a sense of shame. You are not the cause of your depression or your inability to focus. However, the last step must be to escape the identity of a diagnosis.
Forming an identity can risk explaining away any negative states or natural uncertainty. It becomes increasingly difficult to disentangle the unavoidable suffering present in a healthy balanced life, and the idiosyncrasy of one’s perceived psychiatric state. It becomes hard to remember that psychiatric diagnoses are categorical only insofar to separate medical billing codes and are not an objective categorical state on the level of experience.
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Debunking the ‘serotonin hypothesis’ in some ways is meta-analytical and academic. People’s individual experience is infinitely varied and for some the ideas put forth here may be extremely validating. For others, it may be heresy that completely contradicts their personal experience. The main objective of re-evaluating the serotonin hypothesis of depression is to usher in a level of open-mindedness into psychiatry without tunnel visioning onto chemicals and neurobiology which may be the natural inclination of our atomised and technologically inclined discourse.
