a science in need of a theory

I've had a number of people wonder why, as someone with a research background, I'd be interested in psychiatry. There's a tendency to view psychiatry as 'fluffy' and not something that would be interesting to a person who has spent years getting down and dirty with cells and proteins.

In my view, psychiatry is truly biomedicine’s last frontier, and no medical specialty could be more fascinating for someone who loves unanswered questions.


Medical science can speak knowledgeably on a molecular and tissue levelabout the causes of diabetes, asthma, and cardiovascular disease. We can trace Type I diabetes from the death of a specific cell type (pancreatic beta-cells) through the loss of their hormone product (insulin) to the immediate result (inability to use and store food energy) to the final result (death, before insulin was widely and cheaply available). We could tell you another good story about heart disease: fatty deposits build up inside the arteries that feed the heart, narrowing their cavities until they can be clogged by small bits of clotted debris, starving the heart of blood and resulting in the death of its muscle tissue - a heart attack. (Yes neither story is so simple, in a nod to the endocrinologists and cardiologists out there - but let's not get bogged down in details.)


However, the DSM-IV lists not one disease for which such a clear pathophysiological chain of events has been established. When faced with depression or schizophrenia, medical science begins to wave its hands, to stutter and mumble vaguely about deficits or excesses of this or that neurotransmitter. In this sense, psychiatry is truly biomedicine’s last frontier.

Sure, we have some vague hypotheses about things. Take for example the 'dopamine hypothesis' of schizophrenia. That's the hypothesis that schizophrenic patients have too much dopamine in the frontal cortex (resulting in positive symptoms like hallucinations and delusions) and not enough in the subcortical areas (resulting in negative symptoms like social isolation and flattened affect). That explains why dopamine-blocking drugs improve the positive symptoms but aren't so great at fixing the negative ones.

That's a nice finding, and it is likely accurate to a degree; but it's not what you would call pathophysiology. That's like saying the problem with my computer is that it's got too much electricity in the hard drive and not enough in the disk drive. The computer doesn't work by bathing its various parts in electricity, and neither does the brain work by bathing its various parts in neurotransmitter soup. The important thing for each of them is the patterns in which the circuits are communicating with each other, and naming the medium of that communication - be it electricity or dopamine - isn't anything like the answer to a question about why the system is broken.

But nonetheless, psychiatry continues to offer explanations like "Too much dopamine!" or "Not enough serotonin!" to questions about why people have various psychiatric illnesses.

Many of these answers are based on reverse-engineering from medication effects. We've got this drug that increases serotonin transmission, and it fixes depression, so therefore depression must be the result of insufficient serotonin. We've got this other drug that blocks dopamine transmission, and it fixes schizophrenia, so therefore schizophrenia must be the result of too much dopamine.

The obvious problem with this reasoning is that a drug isn't a perfect reversal of a disease process. A disease has some complex effects, and a drug has some other complex effects, and some of the drug effects work to cancel out some of the disease effects, but the overlap is in no way perfect and doesn't necessarily offer us any information about the root cause of the disease.

When John Snow removed the handle of the Broad Street pump to halt the 1854 cholera epidemic in London, did that mean that working the pump handle gives a person the cholera? No, and neither does 'fixing' your depression with more serotonin mean that depression is ultimately caused by 'not enough serotonin.' Serotonin is playing a role in there somewhere but a 'serotonin deficit' is overly simplistic as a cause of anything so complex as a psychiatric disorder.

So the drugs do a bunch of things, and symptom relief is only part of the picture. I don't really think they're fixing whatever the underlying problem is, only pushing the brain into a more manageable state (not quite a normal one). Although some schizophrenics are quite pleasant and normal when they're appropriately medicated, lots of others are still evidently off.

So what would a theory of psychiatric disease look like - a real one? Don't look at me, I'm just the critic. But this very interesting and timely article in the New York Times describes a couple of authors who have developed something that's much more along the lines of a Good Theory than any of the other vagueness I've heard. I'm not certain I agree with their lumping of psychosis and mood disorders as fundamentally similar, but I like the way they think.

fear of hell

The screech of my pager jolted me from sleep. A soft-voiced nurse informed me that they were having some trouble with one of the patients and his behavior was very disruptive to the others, so could I come by and see him, please?

I asked for some further details. Apparently he was kneeling on the bathroom floor screaming that Satan was trying to remove his soul through a portal in the back of his head.

Yikes. I quickly pulled up the patient's record for a look. He was a young man in his early twenties with a diagnosis of schizophrenia. History of delusions about the devil. Apparently he had presented voluntarily for help with a chief complaint of "getting schizo again." That sounded like an unusual degree of insight for a severely psychotic patient.

I jogged over to the next building and let myself into the locked unit, jiggling my keys about in apprehension. The unit was quiet. I peered into the empty bathroom on my way to the nursing station.

The nurses greeted me with visible relief. "He's in his room, doctor." I walked down the darkened hall toward a square of fluorescent light spilling across the linoleum. I nodded politely to the patient's silent knife-lipped sitter, and knocked gingerly at the door.

He lay flat on his back in the spare, brightly lit room, arms at his sides. Only his wide, terrified eyes moved to follow me about the room. Pale and trembling in his coat of puppy fat, he looked like a round-cheeked child caught in a nightmare. I asked him what was wrong.

He glanced at me sidelong. "Nausea."

Nausea? "Is that all?" He nodded. "Is it all better now?" Another nod. "Are you sure? Because the nurses told me you were having a lot of trouble a few minutes ago." A third fearful, stiff-necked nod. I paused. "Are you afraid that talking about it is going to make it come back?" A vigorous nod. "Okay," I said. "If you don't want to talk about it, I don't want to make you talk about it. But I might have a better chance of helping you if you could tell me what the problem is."

I'd barely finished my sentence when he burst out, "Satan is talking to me!"

Ah-hah.

"What's he saying?"

The patient shook his head, refusing. Sweat beaded his unlined brow. He looked awful. I took his hand. "Can you tell me what's real?" I asked. He looked at me. "I'm real," I told him. "You're real. The hospital is real. My hand is real." I squeezed his damp chubby hand, and he squeezed back, staring at me, and nodded. "Is Satan real?"

"I can hear him talking right now!"

"Tell him to shut up."

"Shut up!" he screamed vehemently at the empty air to the left of his head, startling the others in the room.

"Good," I coached. "Listen to me. Satan is not real. I know this is frightening. But try to keep reminding yourself that it isn't real. Are you okay?"

He nodded. "Are you okay?"

I was confused. "I'm fine. I want to make sure that you're okay."

"You're all right?" he repeated.

"I'm fine," I reassured him, still unclear about the reason for his concern.

He beamed, for the first time, with relief. "So I can't hurt you with my thoughts?"

I understood. "No, you can't hurt me with your thoughts. That's not real, okay?"

He nodded again. "Sometimes I get confused."

"I know. It's okay. If you get confused you can ask the nurses for help, or you can ask for me to come back. Do you want some medication?"

He nodded again. He was already pushing the limits on antipsychotic dosing for the day but the meds didn't seem to be touching him. "You've already had a lot today," I told him. I'm going to give you something to help you sleep, and just a tiny bit more of something else for the voices. But no more today after that, okay?" He was agreeable. "Is there anything else we can do to make you feel safer?"

"Can someone stay with me?"

"Sure." I gestured toward the implacable sitter at the door. "It's Rose's job to stay here and watch you, and she can help you as well if you get scared again."

"No," he cried, suddenly frightened again. "She's with Satan!"

I looked doubtfully at the sitter, who stared back in frizzy-headed indifference. "No she's not," I reassured the patient. "That's not real, okay? She's here to help you just like everyone else."

"Oh, I'm sorry," he said, addressing himself to the sitter. "I get confused sometimes. I didn't mean to be insulting." She nodded silently.

"It's okay," I offered for her. "Everyone here understands. I'm going to go write for the medication we talked about. Do you need anything else before I go?" He shook his head. "Okay. Just remember to ask for help if things get bad again."

“Thanks,” he said, and I stepped out.

This was definitely not toeing the party line on handling delusions. You’re not supposed to challenge the delusion, or even usually imply that you don’t think it’s real – at least not outside of a structured therapy program. (Cognitive behavioral therapy has been found effective in reducing delusions, but that requires a long-term commitment to treatment and a strong therapist-patient relationship.) Normally what you’re supposed to do in an acute situation like this where you don’t know the patient is simply be supportive and offer medication.


On the other hand, this patient had excellent insight. He knew he was ill, and he found his hallucinations and delusions terribly frightening. My instinct was to offer him assurance that his nightmares weren’t real.

For good or ill, this is the way most working psychiatrists function. They are guided, for the most part, not by the studies and statistics of so-called “evidence-based medicine,” but by their own individual combinations of instinct and experience.

This is true even in the realm of psychopharmacology, which is perfectly amenable to randomized controlled trials; but it is especially and unavoidably true for the doctor-patient interaction. This interaction is important in all fields, but in psychiatry it is an explicit and essential part of the therapy. And it is incredibly difficult to quantify.

Two therapists may use the same method but achieve radically different results. The most important factor in the success of the therapy is the individual therapist – not his degree, not his school of thought, but just his individual character. It’s a bit sobering to think that one’s ability to do this job well is so dependent on innate talent. Why all this education if the job isn’t one that can be learned or taught?

I hope my intervention with the patient in this story was helpful for him. In the long run, one short interaction with an on-call resident isn’t likely to have much of an effect either way. But it’s more than a little unsettling to realize I’ve undertaken such a journey with no compass or road map.