I’ll tell you what’s been keeping me up nights. And I know you’re going to say, “Edward, get a life.”

It’s the firewall between mood disorders and psychosis. Emil Kraepelin, the great German psychiatric diagnostician, erected the firewall in 1899 when he said that psychotic disorders (“dementia praecox”) deteriorated progressively to dementia, and mood disorders oscillated between sick and well, not deteriorating. 

This firewall has been gospel ever since, and is not really bridged with makeshift diagnoses like “schizoaffective disorder” that presume the patient really is crazy.

What keeps me up at night is my reading. I read all these historic accounts of patients with psychosis and depression, and the patients seem to have both. Typically, the illness starts with depression or mania, then segues into psychosis, then segues into dementia.

What’s up with that? Are these patients really mood-disordered, or do they have “schizophrenia”? (I put quotation marks around schizophrenia because there really is no disease called schizophrenia, comparable to mumps, but the term has rooted itself inextricably in psychiatry, like a giant weed.) And why do the patients so routinely progress to the kind of disintegration of the personality we call “dementia”?

That was a hundred years ago.

What I do know is that these patients can’t have disappeared. We see them historically very clearly. But we rarely see them today, and the mixed diagnosis “post-psychotic depression” that was in DSM-4 disappeared in DSM-5!

If we don’t see them, maybe it’s because we’re wearing blinders. There are several kinds of blinders:

1. True faith. The Kraepelinian dichotomy between schizophrenia and manic-depressive illness impressed everyone so hugely that whenever melancholic patients developed psychosis, the clinicians scratched out “depression” and wrote in “schizophrenia.”

2. The DSM blinders, which let in almost no light. DSM-3 in 1980 made this problem a lot worse by insisting that affect and psychosis were separable. The late Alexander Glassman had proposed in 1975 that psychotic depression was an important entity, but it got only lip service from the DSM crowd.

3. The “piles of profit” blinders. Big Pharma came out with “antipsychotics” in 1954 (chlorpromazine, marketed in the US as Thorazine). They followed with “antidepressants” in 1959 (imipramine, marketed as Tofranil). These agents are plenty effective. Don’t get me wrong. But they’re effective for lots of indications, not just “psychosis” and “depression” respectively. Chlorpromazine, for example, is an excellent antidepressant. But Pharma marketed relentlessly the idea that these diseases, psychosis and depression, were as different as chalk and cheese. Sales of both drug classes climbed into the billions of dollars.

So when I wake up groggy in the morning, from the nightmare that the same underlying illness may spin off psychotic symptoms at one point, and depressive symptoms at another, I’m quickly comforted by looking at my pharma stocks . . . .

Quick update: The forces that wish to divide mood from psychosis are almost irresistible.

First, there are the profits riding on this continued division.

Then there is the intellectual inertia inherent in the very majesty of the Kraepelinian system: two great diseases, divided by a firewall. This is comparable to the majesty of the Darwinian synthesis on evolution: It had to be true!

Finally, there is the reality that in the world of clinical medicine, yeah, there are some patients who are mainly depressed, others who are mainly psychotic. Not hard to keep apart (much harder to keep apart schizophrenia and depression’s terrible twin: mania. A classic 1974 article shows how difficult that is (Taylor et al., 1974). So mood and psychosis are different kinds of symptoms.

But when depression and psychosis occur in the same patient there may be some deeper illness down there driving the whole train forward. And it is not “schizoaffective disorder”!

There is this nagging feeling that the brain has outsmarted us, that there are real illness entities that we see all the time in the clinic but that we have not understood. The DSM categories have got parts of the elephant’s leg, while the beast continues to tower over us.

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