A Story of Depression as a Disease

Is there a difference between these statements: “I have depression” and "I am depressed?" The first sentence describes something lasting, possibly chronic. The second one describes the state of the person's brain and mind.

As Jonathan Shedler pointed out, the first description provides an illusion of an explanation of why the person is distressed: “Why do I feel this way? Because I have an illness called “depression.”

Can we pause here for a moment? This is not an accident that we talk about depression as a disease. We have been taught to do so. How?

Programming by language happens all the time in our culture. For example, we speak Starbucks: “I’d like a grande-soy-latte, please.”

In Chapter 4 of Ethan Watters’ book [1], McGill University professor Laurence Kirmayer and Keio University Professor Junko Kitanaka shared a remarkable account of how one of the stories of depression was written in Japan [1]. Before the 1990s, there was no word in Japanese for mild-to-moderate depression; and the sales of selective serotonin reuptake inhibitors (SSRIs) were zero, while the sales were approximately 13 billion dollars per year in other countries combined. Then, GlaxoSmithKline, the manufacturer of Paxil, started a massive marketing campaign. Two of their campaign's key messages were that depression was a common disease caused by a chemical imbalance in the brain and that “antidepressants” restored the balance. As a result, the sales of Paxil in Japan reached the level of a billion dollars per year by 2008.

One of the components of this story was the term “antidepressant,” which has been used in the USA since the 1950s. This term is attributed to Max Lurie, a psychiatrist in Cincinnati [2]. He referred to isoniazid, a monoamine oxidase inhibitor (MAOI) as an “antidepressant.” Thereafter, all pills prescribed for depression have been called “antidepressants,” including selective serotonin reuptake inhibitors (SSRIs). In labeling isoniazid as an “antidepressant,” Dr. Lurie did something quite customary in medicine (consider anti-inflammatory or antinausea medications). However, he was influenced by the story that depression was a disease, which led him to use medical terminology.

The prefix “anti” creates an impression of a dichotomous system, where the disease drives the pathological process forward, while an “anti-depressant” drives it back to health.

Here is what I think happens when people hear the term antidepressant: “There is a clear-cut thing, called depression. Depression is a disease, caused by a chemical imbalance in the brain. A cure from this disease is an “antidepressant” – it restores the chemical balance.”

Then, there is a twist:

“When your antidepressant didn’t work, we will consider your depression to be 'treatment-resistant.' Why? Because the anti-depressant was supposed to work. The very name suggests so. The only reason why it didn’t work was that your unruly depression was 'resistant.' Then what? Electro-convulsive therapy (ECT). Still resistant? Ketamine. Resistant still? Surgery.”

Please note that “treatment-resistant depression” was defined in the 1970s as a person’s lack of symptomatic improvement in response to two different courses of “antidepressants” [3]. Therefore, the term “treatment-resistant depression” assumes that anti-depressants are supposed to work. Such a definition is an example of circular logic – you define a drug based on the disease, and then you redefine the disease based on the patient's reaction to the drug.

Now we know that there is no causal theory of serotonin imbalance leading to depressive symptoms [9], and the evidence of the efficacy of SSRIs for depression is weak – it is three times lower than that of psychodynamic psychotherapy [4].

If the tale of depression as a disease is misleading, what are the alternatives? Jonathan Shedler suggested a useful metaphor – a fever. Fever is a non-specific state – it is common in various conditions. Flu, on the other hand, is a disease and we know its etiology (a set of causes) – it is a viral infection. Shedler suggested that depression, like fever, is a non-specific state, not a disease.

We know that Tylenol treats the symptom (fever) but does not cure the flu. Treating symptoms is important [5], as we could die from hyperthermia, but we need to know that the immune system cures the flu, not the Tylenol. Therefore, it would be misleading to describe a lasting flu as “treatment resistant” based on it not responding to Tylenol.

In addition to Shedler’s metaphor of a fever, an integrated, causal model of depression as a state was proposed in 2009 [10], and then further elaborated and refined [6, 9]. This model comes from Affective Neuroscience by the late Jaak Panksepp and his colleague Douglas Watt, as well as Mark Solms, Maggie Zellner, and others [6, 9]. It is called the "separation distress hypothesis." Some of the ideas in this model go back to Sigmund Freud and John Bowlby, but Pansepp and Watt made critical multidisciplinary contributions.

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Summarizing the separation distress hypothesis here would not do it justice, as it is reasonably complex (so is the phenomenon it represents). You can find the latest update and systematic review of this model here [9]. The separation distress hypothesis combines innate, developmental, biological, psychological, and environmental factors. It does not reduce the macro phenomenon of depression to a molecular level of serotonin while ignoring all the levels in between. By now we have accumulated considerable evidence from multiple perspectives in support of the separation distress hypothesis [see 9 for a comprehensive review, as well as 6 and 8].

Repeated experiences of neglect, abuse, or abandonment in childhood, maladaptive habits, sleep disturbance, acute traumas at any age, complex trauma, and other factors can all lead to the patient suffering from repeated episodes (states) of depression. As you can see, depression, like fever, is non-specific and there are many possible pathways to it. It is biological and psychological at the same time.

What might the shift to the separation distress hypothesis result in? First, the dominant chemical imbalance story would have to be de-prioritized. An alternative understanding described by Mark Solms and his colleagues is that the feeling of depression means something [6,7]. Solms reminds us that this is not a new idea in medicine. A sensation of acute pain in the leg means that there is possibly a laceration there. Nausea means a possibly upset stomach. These “messages” guide us to what the problem is and where.

One of the meanings of depression, according to Mark Solms, is that our normal need to feel cared for is unmet [6, 7]. We feel painfully alone, unattached, or abandoned. This message is something we can notice, acknowledge, and work with in psychotherapy. Further, there are meaningful psychological reasons why the patient feels depressed, episodically or chronically. There is a way to discover in psychotherapy how this state came about and then work together with the patient to get to a stable resolution of this problem.

Using an etiological approach to depression would allow us to focus on the causal treatment that has shown significantly higher efficacy than SSRIs [4].

It is worthwhile saying that the separation distress hypothesis, like any other theory, has some limitations. For example, it lacks cultural sensitivity. However, I believe that this etiology-based, integrated model is more beneficial in guiding treatment choices for depression than the "chemical imbalance" model.