Wednesday, November 12, 2008

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.

Tuesday, November 4, 2008

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!"


"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.

Friday, September 19, 2008

disciplinary medication

Disclaimer: I am not a child psychiatrist and do not speak with professional authority on this subject. These are my own ideas based on various readings and personal experiences.

Everyone loves to hear about someone overcoming obstacles to become a star. This NYT article about Michael Phelps, ADHD-child-turned-Olympian-superstar, caught my eye.

I found most intriguing the bit where Phelps’ mother says that, although he was incapable of sitting still for five minutes in school, he was able to sit patiently at poolside for hours awaiting his chance to swim.

I've heard many stories like this about ADD/ADHD/CD/ODD children: unmanageable under the stringent circumstances of formal schooling (sit still, don't move, don't talk, pay attention), they blossom under circumstances that channel and challenge their natural energy.

In fact, one research team has come up with interesting results suggesting that children with ADHD benefit from exposure to natural settings (Kuo and Taylor).

All this leads me to suspect that this entity which we treat as a disease may actually be a personality trait that lies on the normal spectrum, but that happens to be incompatible with the demands of our technological society.

Human beings evolved to forage, track game, and avoid becoming prey. Those are the tasks for which we were optimally designed. Sitting quietly in school for six to ten hours a day is not in that job description. Humans are amazingly flexible, so most of us can handle it to a greater or lesser degree; but it's not surprising that those out on the high-energy end of the personality spectrum are having some trouble.

So does that mean that we should not diagnose or treat ADHD?  If in another place and time it would have been simply a character trait, does that mean we shouldn't medicate it?  Well, I wouldn’t say that either. Some of the behaviors described for these kids are absolutely beyond the pale of what parents and teachers could be expected to manage by themselves.

Whether these behaviors would be different in a different environment – out on a farm, say, or in a forest – is perhaps irrelevant. We can’t move the kids out of the society they’re in. This is it, for better or worse.

And as always, I’m all for behavioral interventions ahead of pharmacological ones. If the behavior of kids on the milder end of the spectrum can be improved by fixing their diets or letting them tear around outside for a few hours, then that’s an easy decision to make.

But what about kids on the extreme end of the spectrum? The kids who scream, bite, kick, punch, and cannot be coaxed, bribed, threatened, or punished into any semblance of normal behavior?  This is the difficult question faced by parents of ADD/ADHD children: to medicate or not to medicate?

I’m generally extremely wary of giving psychoactive medication to children. The brain is not completely developed until the mid-twenties, and the brains of young children adapt gleefully and abundantly to changing stimuli. If those stimuli include, say, an extended period of dopamine blockade, the brain will adapt by upregulating its sensitivity to dopamine, attempting to restore a more typical balance of dopamine activity.  How long do these effects last? Nobody knows.

Even for the best-studied drugs, there's more information available about gross parameters like height and weight than there is for long-term psychiatric effects.  E.g., Ritalin has been around for a while and is relatively well-studied in children.  At this point it's pretty clear that Ritalin does not have gross effects on children's overall growth and development. I'd be more concerned about subtle long-term changes to their mood and behavior. These things are of course significantly harder to study.  I did find some studies looking at behavior in adult animals who had received psychoactive meds as juveniles.

Here’s a study that shows rats that get Ritalin as adolescents are more sensitive to amphetamines as adults. (Valvassori et al.).  Here's another one that demonstrates the same thing, and also suggests some baseline behavioral changes (Carlezon et al.).  Similar results in this third study (Brandon et al.).

This was later studied in humans and it doesn't look like kids treated with Ritalin are any more likely to become speed addicts as adults than anyone else (less actually), but I'm not aware of any follow-up on, e.g.,  long-term susceptibility to depression or other mental health concerns.

Meanwhile, children are starting to receive medications with much less pediatric data behind them than Ritalin.  For example, the FDA approved the antipsychotic Risperdal for use in children based on three clinical trials that lasted 3, 6, and 8 weeks respectively.

(Risperdal is not approved for use in ADHD specifically but is sometimes prescribed off-label for that indication.)

Huh? Where’s the study that looks at the kids five, ten, or twenty years later? That’s the one I want to see. And barring that (given the difficulties of conducting such extended trials), I’d love to see some more animal studies.

So about those animal studies.  I didn't find many, and what I did find wasn't encouraging. Here’s a study that shows alterations of development, outgrowth, and axonal migration in developing worms receiving antipsychotics (Donohoe et al.).

Unfortunately, the need for behavior control is urgent, and the information just isn’t out there. I think the vast majority of parents are pretty cautious, as they should be, about medicating their kids, and will do so only as a last resort. I also think that’s the right approach; and in the final analysis, if you need it, you need it. Sometimes you have to trade the threat of an unknown outcome in the future for a drop of sanity in the here and now.

But I wouldn’t be soothed into thinking that just because we don’t know about long-term ill effects of childhood medication doesn’t mean they don’t exist. You can only know something is there if you look for it, and that’s something the biomedical research community doesn’t yet appear to have done.

Sunday, August 31, 2008


A new patient walked into my psychopharmacology clinic last week. She seemed reasonably typical at first. A line in the chart noted that she was somewhat wary of psychotropic medications, but then many patients are, and I don't tend to mind that attitude myself since I also subscribe to the less-is-more theory of psychiatric meds.

She was on a fraction of the normal dose of a common antidepressant, which, she reported, was her only medication. It seemed unlikely that this small dose was having any effect, positive or negative, on her mental health; but her mood was stable and she was sleeping and eating well. Things looked good. The main points covered, I asked if she had any other concerns.

"Well, I had my brain imaged," she offered. Brain imaging? Did she have a neurological disorder I hadn't known of? I asked which physician had ordered the tests.

"Oh, I did it myself. I saw it on TV and thought it would be a good idea."

Brain imaging advertised on TV, direct-to-consumer?

She handed me a sheaf of papers, of which the first few pages read like Baby's First Book of Neuroanatomy crossed with the New Age Guide to Herbal Remedies. "Prefrontal cortex: Planning ! Attention!... L-tyrosine!... Anterior cingulate: Cooperation! Flexibility!... St John's Wort!" There was then a list of "hyperactive" and "hypoactive" regions in this patient’s brain.

She'd paid out of pocket to have her brain SPECTed at a clinic that advertises on late-night TV.

Where to begin.

Let me just state up front that there is no established role for brain imaging in psychiatry at this time. None. You can't look at a picture of blood flow (or any other parameter) in the brain and make a diagnosis. (SPECT has some utility in distinguishing Alzheimer's from vascular dementia, but that's more neurology than psychiatry.)

To start out with, despite the existence of a number of studies looking at blood flow in depression, there is not a clear consensus on which areas of the brain are most involved.

Then, let me point out that we have no standard against which to judge baseline levels of regional activity. Blood demand fluctuates on a moment-to-moment basis depending on what the brain is doing at any particular time. The variation in demand between individuals and times is not very well described. So my patient's brain regions were over- or underactive compared to what? Somebody else's brain thinking sad thoughts? Her own brain thinking happy thoughts? The average of ten other people's brains doing a crossword puzzle? Any way you slice it, it doesn't sound informative.

Even when looking at more stable and reliable imaging correlates of clinical depression, in which a clear average population difference exists between depressed individuals and normal controls, there is so much overlap between the two groups that you can't usually infer a person's mood from his brain scan alone. Check out this graph from a review by J.H. Meyer, showing MAO-A density in different brain regions.

While there are clear differences between the populations on the whole, it's also just as clear that an isolated brain scan likely won't tell you much about whether that individual is depressed or not. There are just too many people in the overlap region.

As you can tell from these links, science is still in the phase where we use clinical data as the gold standard against which to judge the validity of imaging results. Going the other way round - starting with the scan and inferring the diagnosis - is something that's far away from our current level of understanding.

Consonant with this, the 'interpretation' of this woman's SPECT scan was nothing you couldn't have figured out from talking to her for a few minutes. After citing a number of areas in which 'dysfunction' was discovered by the SPECT scan, it described some related problems she might have, such as "negativity, guilt, blame, irritability." The kinds of things you could diagnose more easily from a cheap interview than from an expensive brain scan.

The recommendations included a number of OTC supplements (without indication of dosage, of course, since these supplements are largely unregulated, little is known about optimal dosing and in any case actual content may vary wildly from what's written on the label). Some of them were items that have some evidence for their utility (e.g., omega-3 fatty acids); others seemed relatively benign (e.g. Coenzyme Q10) but with little available evidence regarding their use in depression; and others (e.g., St John's Wort - see this FDA advisory) can be positively harmful under the wrong circumstances.

My patient was on all of the recommended supplements - some six or seven different pills - despite having declared the Lexapro as her only medication. This is an incredibly frequent error made by patients, who are soothed by the 'supplement' label into thinking the items are somehow safer or less likely to produce side effects than chemically prepared medications. In fact, there are a number of supplements that have produced significant health problems in their users (e.g., ma huang, which was ultimately banned by the FDA), and since their preparation is poorly regulated, both the dose of the medication and the number and identity of the compounds present are pretty much up for grabs. These facts make supplements a rather riskier bet than prescription preparations.

There were some other very general recommendations of the type that any mainstream psychiatric practitioner would typically make: cognitive behavioral psychotherapy, good social and emotional support, exercise, self-relaxation, and a balanced diet without excess use of nicotine and caffeine. All useful advice, none of it requiring the service of gamma ray scans.

I fully expect that brain imaging will one day have a place in psychiatric practice. However, that day is not today, and I find it upsetting when my patients are conned into paying good money for a useless procedure, a dose of radiation, and some occasionally inappropriate advice.

I do find it curious that so many people place deeper trust in the uncharted waters of alternative medicine than they do in the well-documented, frequently evidence-based recommendations of the standard medical establishment. Things aren't always peachy in the world of traditional medicine; doctors have done a lot of harm as well as a lot of good. But I like to think that as a profession we ultimately learn from our mistakes, and I'd submit as evidence the enormous strides modern medicine has made in extending the productive lifespan, reducing infant mortality, etc etc etc. And in a plug for my own specialty of psychiatry, although there are many patients who are beyond our present capacity to help, I know many others who have unquestionably been saved from suicide or from personal and social destruction.

When someone shows me a randomized controlled trial that demonstrates the utility of a supplement, I'll be happy to use it and recommend it. (I already do recommend both fish oil and melatonin under the appropriate circumstances.) Until then, it's just a black box; and that's not something I'm comfortable giving to a patient.

Tuesday, August 26, 2008

mind control II: yours

I wrote last week about how surprisingly simple it can be to turn around an angry patient. Two small words hold the key to taming the beast: "You're right." Those words are like a magic tonic, a soothing balm. The patient drops his offensive posture, loses his hostile glare. His hackles soften. His ears are open, receptive. Magic.

But it's not enough merely to mouth the two magic words. You need to believe them, to find the grain of truth in the patient's angry accusations and hold it up to the light. Typically that grain of truth contains a failing of your own. That's hard to admit.

In the CBT group I attend we use role-plays as learning tools. We mimic angry patients, throwing harsh words at our colleagues as a challenge to their empathetic skills.
It's curious that even when you are merely acting a role, pretending to be upset, you can feel in yourself the good or bad reaction to the 'therapist's' words. Defensiveness from the therapist provokes further heights of anger. But the crucial initial words "you're right" produce a rush of surprise and disarmament, a shock of pleasure at being understood, a hint of gleeful righteousness, and an intense curiosity and complete willingness to listen to what's coming next.

Rookies never get the task right the first time, or even the first ten times, even after having the strategy thoroughly explained and seeing more experienced members employ it. They simply can't get themselves to say, "You're right; I've failed; you're understandably angry; but tell me more so I can try to fix it." Instead they mouth platitudes like "I hear that you're frustrated," or "Why don't you calm down so we can discuss this," or they get defensive and explain why the patient is wrong to be angry. These strategies are all, of course, bound to escalate the situation.

Never, never on the first try do they plainly acknowledge the patient's anger and the faults of the therapist. I sure didn't, and I've yet to see any other rookies manage it either. It's suspiciously simple, yet incredibly difficult to do.

As I mentioned last week, I've been using this strategy on belligerent colleagues and other assorted meanies as well as on patients. It's been absolutely foolproof so far. But interestingly, when I shared the strategy with some of the psych residents who are not in the seminar, I met stubborn disbelief.

"I don't think it's appropriate to just subdue yourself to the demands of the patient. You have to maintain your own integrity," one woman said.

She'd verbalized the gut resistance to this strategy that comes from your own ego. That's exactly why it's so hard to implement, despite being so simple. Because you have to lose in order to win. You have to cave in order to prevail. You have to drop your ego in the dust and squish it with your toe in order to have any hope of success.

Even in the false environment of the role-play, where your partner flings made-up accusations at you, it's hard to accept and apologize for these acts you didn't commit. In that setting it's really just a script you could recite with no personal involvement whatsoever. "You're right, I did [fall asleep during your session/give you the wrong drug/insert horrific therapeutic sin of your choice], I bet you're feeling really angry right now." That's it, and with minor variations it's pretty much always the same. Yet it takes a long time to be able to do, even under laboratory conditions. How much harder is it when it's truly your own actions that are being assaulted.

Seeing the patient's anger as a threat to your ego integrity is losing sight of the goal of the therapy, which is to help the patient. The goal is not to maintain your own sense of dignity and self-worth; presumably you've already got a healthy dose of those or you haven't any business trying to therapize others. And if you consistently put the goal of preserving your dignity ahead of the goal of helping the patient, you'll have a lot of frustrated patients and that won't be good for your ego as a therapist in the long run anyway.

But we're accustomed to working hard to maintain our dignity and self-worth, because people without them are racked with doubts and insecurities and generally have a difficult time in life. So we're pretty well programmed to protect our egos, which we do in different ways depending on our basic characters, stages in life, and how we frame ourselves to ourselves. But we all do it. When faced with a blow to our egos, we're socialized to parry it, swiftly and surely.

However, it's all too easy to forget that an interaction between a therapist and a patient is not the same as a typical social situation. Your goal is to help the patient support and develop his ego, not to prop up your own. But when faced with a threat, it's instinctive to forget that, and to fall back on the strategies that have always been helpful (defending or rationalizing or denying your actions, deflecting the blame, etc.).

Hence my colleague's assertion that it was important to maintain one's own integrity. But important for what, I'd ask? Important for the patient, I suspect she'd say - to set limits, to teach the patient how to behave calmly and fairly. But the key point here is that there is always a reason for the anger. Truly isolated, reasonless, purely biological anger is a rare thing that occurs with specific brain lesions, typically affecting the hypothalamus. Real humans in the real world have triggers, and if the patient is lashing out at you it's likely that you're at least part of the trigger. It's your job to be the level head and figure out what that part is and what you can do about it. Otherwise your chances of getting the patient to a state where he can be calm and fair are going to be on the slim side of nonexistent.

Sunday, August 24, 2008

mind control I: theirs

I'm in a seminar that meets once a week to educate ourselves in the technique of CBT (cognitive-behavioral therapy). This is only one of a plethora of available therapeutic modalities (dialectical behavioral therapy, psychodynamic, psychoanalytic, etc etc etc).

We're learning specific, codified techniques for making our interactions with patients productive. Some of them are very simple; but the results are absolutely amazing.

One of the things that attracted me about psychiatry was how smooth the attendings were about dealing with difficult patients. You'd have an obnoxious patient on the medicine or surgery floors who would have all the docs chewing their stethoscopes with utter frustration. Then the psychiatry consult would walk in and in three minutes he'd have the patient eating out of his hand. Unbelievable. I wondered whether this was a talent they were born with or a result of their education. (Ultimately, as with most things, it's probably a little bit of both.)

It's a bit of a chess game, as one has to think a few moves ahead. If I say this, he'll likely say this. If I don't say this, another chance may not come. If I say it in this particular way, will he react well or badly?

It's perhaps funny to imagine that human interactions could be condensed down into a set of algorithms. One would like to think that individuals are so very different from each other that one size could never fit all. And it's true that one needs to apply one's interpersonal intuition to an extent. But only to an extent. There are definite ways to bring angry or frustrated patients back to a state in which they can engage in rational conversation.

And it doesn't only work in the controlled environment of a hospital or clinic. I've used some of the basic techniques we're learning with other angry, irrational people in my life (mainly frustrated residents from other services) with excellent results. Secret weapons! Psychiatry is incredible.

Next entry: Getting people to be rational is both easier and harder than it seems.

Thursday, July 10, 2008

biology vs psychology: false dichotomy?

I was speaking with a very intelligent and insightful patient today who mentioned that he'd felt his problems (depression, some obsessional traits, a mild eating disorder) were all 'psychological' until he found a drug that significantly improved them. From that point on he was convinced they were 'biological,' and embarked upon a quest for the Magic Pill that would solve all his neuroses at a single swallow.

I see references to this sort of split all the time, and not just from patients but also from highly educated physicians and scientists. Somehow they consider that our behavior* arises from two distinct sources: one composed of neurons, synapses, and neurotransmitters, and another composed of experiences, drives, and willpower.

If you buy the biological theory of behavior at all, then it makes little sense to imagine a dividing line between 'biological' and 'non-biological' causes of behavior. Experience alters neurochemistry just as surely as medications do.

Here's a nice (but somewhat technical) piece of work discussing some of the cellular-level changes that have been observed to be triggered by real-world experience (Takahashi, Svoboda and Malinow).

Evidence abounds for the utility of 'talk therapy' in psychiatry. In order to separate the 'biological' from the 'psychological,' one would have to believe that there exists an entirely separate underpinning of human behavior that operates on some ethereal plane, unrelated to the biomechanical world of synapses and neurotransmitters.

If you're going to accept that neurobiology underlies behavior, then there is no clear point at all where you can divide the biological from the psychological. If you accept that experience exerts its effects through alteration of our neuronal activity, and you accept that hearing your therapist is an experience, then there is no room for some nebulous 'non-biological' effect. Your therapist's words tickle your ear neurons, which tickle your brain neurons, which make subtle changes - sticking themselves to some of their neighbor cells, unsticking themselves from other neighbors, changing the rate at which they spit neurotransmitters at each other - and voila! You change your behavior.

That the line between biological and psychological is fuzzy to the point of nonexistence is indeed starting to permeate the general consciousness, at least to a degree. This usually arises in discussions of ethics, where the whole edifice of crime-and-punishment rests on an assumption of free will. This assumption is being radically challenged by evidence that our behavior is heavily determined by factors not under our direct control (genetics and medication in particular).

This opens up another can of worms, because we frequently associate 'biological' with 'beyond our control' and 'psychological' with 'within our control.'  Hence my patient (and many like him) and his Magic Pill search.

But I think the educated world at large is not yet ready to join Steven Pinker in declaring us will-less playthings of our genes and environment. Fine for now, but I'm curious to see what we'll make of coming scientific advances that will no doubt push us even closer to the will-free wall.

*I'm using "behavior" intentionally to encompass all of the workings of the human brain that are manifest to others. I'm doing this very deliberately because the question of whether mind is biological at all is a very sticky wicket and not something I can afford to get into in this limited space.

Wednesday, July 2, 2008

free will and eating disorders

We've a number of eating-disordered patients on the unit at the moment.  Eating disorders have never been a particular interest of mine; yet as I work more closely with eating-disordered patients, I've come to realize their problems raise a number of interesting philosophical questions.

We've all had the experience of being of two minds.  We want something, yet we do not want it. One experiences this on a regular basis, yet it rarely disturbs the view of oneself as a single, integrated ego, a unified mind.  However, the problem is very severe in the eating-disordered.

How to want to be well but also not want to eat?  How to want one's life back, to know that the eating disorder has wrecked it, to understand that one flirts with death, yet be so petrified of food?  Even my patient Ms. G., weighing just 35 kilos and desperate to regain a normal life, was yet utterly unable to prevent herself from binging, vomiting, and binging again.  "Obviously I have free will," she wailed unprompted, "but somehow I can't stop doing it."

Our medical student was surprised at her intelligence, unable to credit her self-destructive behavior because "but she's so smart!"  But 'smart' has nothing at all to do with it; in fact, quite the opposite: anorexics may have higher than average IQs.

(This may be tied to the well-documented association between anorexia and the need for control.  Besides body weight, academic achievement is another area where due diligence generally yields the desired results, and thus appeals to the controlling anorexic personality.  In fact, Dura et al. note that 'perfectionistic striving' actually yields better academic results for anorexics than would be predicted by their IQs alone.)
This makes a degree of sense when one considers that a certain level of complexity is required in order to deny one's own basic drives so severely.  At the most straightforward level of functioning, one merely obeys one's basic drives - hunger, thirst, fear, desire - pursuing the most immediate means of gratification.  At a somewhat more sophisticated level, one may delay instant gratification for a bigger payoff later on, forgoing one candy now for two candies later.  Ultimately, one may come to value successively loftier intangibles above the basics: staying up late to finish that big paper; starving for one's art; giving one's life for one's country.

Well then, how to be cognitively impaired, like our patient Ms. S., and yet have an eating disorder?  Ms. S. had been impaired since birth, and she behaved for all the world like a sweet and coquettish child, grinning impishly at the team, asking for hugs, requesting praise for her accomplishments.

At first I could not believe someone functioning at this simple level was sophisticated enough to have an eating disorder.  I thought she must have an organic illness, a food sensitivity or irritable bowel.  And yet as we weaned her down to the most elemental and gastroenterically benign food supplements it became clear that the problem was not in her bowel, but in her head.  She played all of the typical eating-disorder games: saving food, dumping food, vomiting food, mixing and freezing and thawing and refusing it, drinking gallons of black coffee and diet soda, and on and on and on.  

Ultimately it became clear that at least one of the reasons for Ms. S.' eating patterns had, unsurprisingly, to do with control - a common theme among eating disordered patients.  In Ms. S'. case, though, it was more to do with control over her family than over her body.  Still living with her mother in her forties, Ms. S. yearned to go out and build her own life.  She found that refusing to eat allowed her to exert a measure of control over her large, loving, yet stifling family, all of whom rallied round her and raised a ruckus of attention over her malnourished status.  Which was, evidently, far preferable for Ms. S. than sitting quietly on the couch watching TV all day and being ignored by those with lives of their own.

I hadn't given Ms. S. nearly enough credit for the complex, multilayered psyche she evidently possessed.  Humans are deep creatures, even the simplest of us.  

Not too much can go wrong with a simple machine like an abacus or a bacterium.  But as you add more bits and parts and cogs and circuits and cells and networks, the number of ways things can go wrong explodes.  Ultimately you end up with personal computers and human beings, both of which are endlessly surprising and infuriating in the sheer number of things that can go wrong with them.  Hence computer wizards, and psychiatrists.

chemical love

One of my more interesting recent patients had a problem straight out of a daytime talk show. This was a young gay man in love with his heterosexual roommate. The two of them had a very close relationship, eating dinner together, going to movies as a couple, and generally engaging in very couple-like domestic activities. They also had a surprisingly open relationship. The gay man had confessed his ardor to the roommate, and the roommate, while he did not return the sexual feelings, was mind-bogglingly relaxed about the whole issue and the two of them remained as close as before.

Matters took a turn for the worse when the roommate acquired a girlfriend. Naturally the gay man could not stand the girlfriend and resorted to drinking alone in his room or going for long drives whenever she was around. Ultimately he became so depressed and consumed by the situation that he was unable to work, could not sleep, lost interest in his hobbies, and finally sought psychiatric help.

At first nobody on the treatment team could understand the situation, and in particular the behavior of the roommate. We speculated that perhaps he was a closeted homosexual who unconsciously returned the feelings, or else that he simply couldn't bring himself to give up the incredibly cheap rent offered by his lovesick roommate (who owned the apartment).

The answer turned out to be a bit more complicated. I sat down with both men for a frank discussion of the situation, and found that, at least to casual observation, their relationship appeared as close and open as had been described to me by the gay patient. Together we dissected the timeline of their relationship. It turned out they had been ordinary good friends until they began to use the drug Ecstasy (MDMA). Over the course of a summer they had used the drug weekly together - rarely with anyone else - in the process cementing a bond that ultimately became more like a love relationship than anything else.

It is likely impossible to convey the emotional power of Ecstasy to anyone who has not tried the drug. Roughly, it works by reversing the direction of the reuptake transporter that vacuums leftover serotonin out of the synaptic cleft. This dumps enormous amounts of serotonin into the synaptic cleft - far more than would ever normally be present there at one time. Just as chocolate cake overstimulates the taste receptors that evolved to detect the more mild and nuanced sweetness of fruit, Ecstasy overstimulates circuits designed to underlie the natural pleasures of romantic attachment and sensory experience.

In a stark demonstration that love really is just chemistry, Ecstasy can make you feel a gush of deep affection for just about anyone sharing the experience with you. It's Cupid's Arrow in chemical form.

In this particular case, these two men overstimulated their 'love circuits' together over and over again for an entire summer. It's no wonder the gay one fell in love with his friend. As for the straight roommate, evidently Ecstasy can't alter sexuality (unsuprising, as anyone who's tried it will tell you Ecstasy has little to do with sexual feelings, and in fact often inhibits them). But it did seem to have triggered many of the other hallmarks of romantic love. The man gazed affectionately at his roommate, expressed all manner of deep and abiding emotion for him, was wracked with guilt for the suffering he'd caused. Everything was there but the sexual attraction.

The chemical basis for emotion is nothing new, and at this point carries little shock value. Yet it is still difficult to believe how easily we can manipulate our deepest emotions with a little diddle to the neuropharmacological machinery.

What was the cure for this young man? Fighting fire with fire, I prescribed him Prozac. Prozac works by paralyzing the same reuptake transporter that is reversed by Ecstasy. Instead of being vacuumed back out of the synaptic cleft when their job is done, the serotonin molecules loiter around in the cleft. The simple way to think about this is that more serotonin in the cleft equals more happiness, duh - though in fact the biological effects of SSRIs such as Prozac are somewhat more complicated than that (see Nutt et al for a useful summary).

As one might expect, then, Prozac blocks the effects of Ecstasy. With Prozac in your system paralyzing your reuptake transporters, a nice fat pill of E has no more effect than a sugar tab. That was one little-known side effect I thought might be useful in this particular patient's case.

A more well-documented side effect of SSRIs is inhibition of sexual function, including the ability to orgasm (see Rosen et al. for review). In addition to this, there are some anecdotal reports that SSRIs such as Prozac have adverse effects on romantic love. This is a much mushier and less well-documented realm. I found nothing about it on PubMed, though I did find a bit of schlock in Psychology Today that discusses the phenomenon. If this latter bit did turn out to be true, I would wonder whether the effect were secondary to inhibition of sexual desire or whether it involved a distinct group of neural circuits.

Based on anecdotal reports from people who have used them, it sounds as if SSRIs may in fact dull the capacity for deep emotion. You don't feel sad anymore, you even feel kind of happy, but the happiness is a sort of pleasant zoning out rather than a meaningful joy. Indeed, by some reports the entire spectrum of emotion is flattened out (see, for example, comments posted by readers on this WebMD blog).

Much has been made of the possibility that we are depriving ourselves of essential human experiences by medicating away our emotions (see, for example, this review of Eric Wilson's book Against Happiness). Of course, many others more articulate than I have also argued the opposite side of the story (see this other review of Peter Kramer's Against Depression).

As is often true, I find myself taking a position somewhere in the middle. I don't want my patient to be zoned out forever, but I can't help but think that he's already had more than enough character-building for a while. A little Prozac in this case is probably a good thing.

Sunday, June 8, 2008

it's all in your head

Psychiatrists - and doctors generally - see two kinds of symptoms.  There are the 'classic' symptoms that have meaning because they signify something we can treat, and the 'off-road' symptoms that don't seem related to any disease process we understand.

In psychiatry, the former are typified by people who are having frank hallucinations and delusions.  I know how to recognize them  - they look ill, odd, off - and how to treat them - antipsychotics, patience, consideration.

Then there are people who report experiences that are just... not what one normally talks about.  I do brief screenings for psychotic symptoms on all of the patients I see, many of whom may have, e.g.,  mood or anxiety issues, but certainly no evidence of a psychotic disorder.  They may be sad or nervous or emotionally disordered, but their reality testing is absolutely intact.  When asked if they've ever "seen things others don't see," or heard things others don't hear, they typically hesitate.  Then they preface with, "Well, I don't think it's relevant..." or "I'm not crazy, but..." and I know what I'm about to hear.

There was the twenty-two year old girl who said "My sister and I see ghosts.  It's accepted in my family, it's not a problem."  There was the sixty-four-year old Vietnam Vet who heard music when he saw mountains.  It was real music, heard aloud, and specific for each peak. 
Musical hallucinations seem to be an entirely different kettle of fish from the angry, insulting voices that are typically heard by psychotic patients.  (Oliver Sacks has written eloquently about music and the brain.)  

In my short time as a psychiatrist I've already heard many variations on these themes.  They seem a class apart from the psychotic symptoms that are familiar to doctors and treatable.

In fact, this sort of phenomenon is seen throughout medicine.  For doctors, there are two types of complaint: those that signify a known pathological process, and those that don't have a cause we understand.  Most doctors put the second type of complaint in the "all-in-your-head" category.  They may be more or less sympathetic to patients with these complaints (often less, and sympathy tends to correlate inversely with the doctor's workload), but they don't know the cause of the symptoms and there doesn't seem to be an underlying disease they can treat, so they're not really interested.

This gives rise to the common complaint among patients that "the doctor doesn't listen to me."  It's not that he isn't listening, it's that he's categorizing your problems as "meaningful" and "meaningless."  If you tell your doctor your skin is turning yellow, he'll be all ears and will likely order a battery of tests.  If you tell him you have a pain in your left elbow that only happens after you eat,  he'll say "uh-huh" and try to move on quickly.  That kind of pain isn't a symptom of any disease he knows of, so he'll file it under "random aches and pains" and turn his attention to more pressing matters.

Of course, patients rarely know the difference between the significant symptoms and the insignificant ones (that's what medical school is for), so they can get understandably upset at getting yes-deared by the doc.

In psychiatry, these sorts of off-road symptoms fall even further by the wayside than do the general medical aches and pains, because they tend not to bother people.  Few people come to psychiatrists complaining of seeing ghosts or hearing music; rather, they accept these things as part of their lives, and the experiences only come to light if they happen to come to a psychiatrist for another reason.

Symptoms can sometimes move from the all-in-your-head category to the now-I'm-listening category when we come up with an explanation or a treatment for them.  A lot of people with the fatigue and joint pains characteristic of chronic Lyme disease got the brush-off from doctors before the cause of the disease (a spirochaete transmitted by tick bites) and the appropriate treatment (antibiotics) were identified.

I doubt we will ever find a 'cure' for the off-road symptoms seen in psychiatry, for the simple reason that most people who have them don't particularly want to be cured.  I would, however, be extremely curious to see whether we might find an explanation.  Are these really psychiatric phenomena, or are they something else?

Friday, May 30, 2008

demon rum

I'm on an outpatient neurology month, mostly a pretty calm scene compared to the inpatient psychiatric wards - until Ms Q arrives on the scene.  Forty-five minutes late for her appointment, she stumbles in on the arm of the fellow, mascara streaking down her cheeks.  "She's intoxicated," the fellow murmurs gently in his refined hint-of-British, hint-of-Indian accent as he steers her to a chair.  

"I hate it, I hate it," she sobs incoherently.  An overpowering odor of alcohol wafts about her.  She has been swigging from a bottle in the car all the way from home, over an hour away.  I shudder at the thought of the unsuspecting commuters who shared her road.

I am assigned to calm her down; my few months' worth of psychiatric education have won me this one.  I murmur soothingly, knowing there is little useful diagnostic information to be obtained from her right now.  She is a blond beach girl, far from home; and it shows in her long yellow hair, bright pink lids and lips, pink toenails in metal-ringed sandals.  "I hate you," she rages.  "I know you're trying to be empathetic, but you don't understand.  Look at you - you're young, you're pretty, you have cute shoes..." She dissolves into a bathtub of drunken tears.  Cute shoes... emblematic of the good life.  I sigh and pat her on the back.  Miss Sunshine, in need of some perspective at the least.

But she is right, of course.  I don't know what it's like to be an alcoholic.  I have worked in recovery programs, and noticed that the addiction specialists with drug histories often seemed more effective than those without.  Regardless of training and other forms of institutionalized expertise, in the addict's own head it is important that his therapist "understand where he's coming from."  All that training is for naught if you can't even get the addict to listen to you.  For people with their own drug histories, that door is already wide open.

One wouldn't expect one's cardiologist to have his own history of heart attacks; nor ask one's internist if he's tried the antibiotic or diuretic he suggests for you.  Yet psychiatry is somehow different, removed from the clearly delineated ethics and protocols that apply in other areas of medicine.  

insight into madness

Mr W, a first-break schizophrenic in his twenties, had looked just terrible on initial presentation.  Flat, near-mute, meeting all efforts to initiate discussion with "No comment," or just a hostile wall of blankness.  Gradually the medications began to work their magic and he became more able to relate to others; but he continued to refuse to discuss his symptoms.  He kept it all inside until he'd been on the inpatient unit for over a month.  Then one day, very carefully, judiciously, circumspectly, he allowed: "Well,  I was hearing people talk and relating it all back to me."

The team psychologist ventured softly, Did you ever hear the TV talking to you?

Mr W burst out in surprised laughter, and it all came tumbling out.  He'd kept it to himself for at least a year.  Said it felt like being underwater, where he would be convinced the people on TV were talking about him; then by dint of effort he would pull himself briefly above the waterline - no that's not true that's crazy -  and then be swallowed once again.

He'd gone traveling through Asia for six months, thinking he could leave behind the stress and deconditioning that, he reasoned, must have been the cause of this - this oddness.  But he found that people on the streets, speaking in languages he did not know, were talking about him.  He was utterly certain of this, though he could not understand their speech.  He had several brief relationships with other travelers, women; but they all ended because, well, "Things got weird." 

He recalled talking with the interviewer when he'd first come in, when he would only say "No comment."  He remembered her eyes looked enormous and he was afraid, certain that if he spoke he would come to some vague and terrible harm.

Delusions - fixed false beliefs, characteristic of psychotic states - call up a whole slew of questions related to knowledge.  We know that we know; but how do we know?  (For an interesting discussion of this question, check out Robert Burton's website and his recent book.)

Mr W was madly curious, he wanted to know everything - and what's a neurotransmitter? and are there other ones besides dopamine? and what part of the brain? and how does it all work?  
All good questions, and ones for which the answers are far from clear.  He was fascinated, scared, but also relieved to know this had a name, that others had suffered from it, that he was not alone in this bizarreness.

It is an incredible treat to speak with schizophrenic patients who have such clear insight into their disease.  Many of the patients we see are old and broken from long years in and out of hospitals and many trials of different drugs, both prescribed and recreational.  Even at the best of times, when they are not frankly paranoid or delusional or hallucinating, they typically cannot or will not describe their experience in any kind of meaningful way.   I was fascinated by Mr W, I could have sat and talked with him for hours about his experiences.  I had a similar feeling when I read Elyn Saks' excellent book, The Center Cannot Hold.  It offers a rare and precious chance to hear an eloquent and clear-minded individual recall the alternate reality of psychosis.

boundary transgressions

I found out for myself, again, the hard way, why 'professional boundaries' are so important.  Cardinal sin - I hugged a patient.  Should have thought twice, then twice again.  He was a thin wreck of a heroin junkie with wise sad gentle eyes behind scholarly horn-rims, sunken cheeks fuzzed with gray stubble, yellow horse-teeth in an occasional bitter laugh.

Strange how some patients leave me utterly cold, without a fig's worth of worry for whether they end up in the gutter or not.  Others take odd hold of me.  I remembered this man from a previous admission, after he'd driven his car into a tree - for the third time.  What was going on behind those sad gentle eyes that could make anyone wish to die so violently?  He spoke from between clenched yellow teeth, a mountain man trapped in a prison made of poppy stems.  Somehow he struck me.  

He was oddly, unexpectedly open in the interview.  He described unbidden his fear, loneliness, abandonment - until his eyes began to well and I quickly reassured him that he needn't speak of anything that would upset him so.  He drew back, but later returned to trying to explain. Finally he offered, "You ever just need a hug?"  He was staring frankly, a challenge perhaps?

Of course, I think that's pretty normal.
He described standing in the same room with his mother and brother and how desperately he'd wanted a hug, but had been completely unable to ask.  
Why not?
The expected cant about manliness, etc.  My heart rushed out to him.
You want a hug?
"Yeah, I do want a hug."  Testing me?  Wanting to see if I would be as good as my word?  Or, instead, if I would have the strength to resist?  I wasn't sure which option was the failing one.
I'll give you a hug.  No turning back now.  But you have to ask for it.  A psychiatrist's trick, or a weak attempt to give myself - or him - an out?  Regardless, he met my eyes.
"Could I have a hug?"
I hugged him, in my office, with the door closed, this man I'd just met; a long hard hug, rubbing his back as I would that of a sister or dear friend who was sobbing on my shoulder.  He smelled of cigarettes and pine bark.

Afterward I asked something inane, like How was that? or Was that helpful?
The former, I think.  He said he felt unsettled, almost nauseated.  I asked if he needed to throw up; he said no.  He said he hadn't had a hug in ten years.  Then he amended it: "Well, a hug from one of your buddies, that's something different.  But a nurturing hug..." He trailed off.  Then, "I haven't touched a woman in ten years."

Uh-oh.  Sirens, alarm bells.  How could I think such an act could stand independently of gender?  Fooling myself utterly.  But not innocently either - would I have done that for a patient I hadn't felt so drawn to?  Honestly, probably not.  Or, just - not.  Then how far could I fool myself to pretend I thought he would take it as such?

Let's get back to the interview.  I sought escape in a return to officialdom - pathetic and weak, as I'd abandoned that bulwark voluntarily already, showing it to be nothing but a sheet of tissue.  But he cooperated, bless him, returning also to the thin fiction of protocol.  

And later, of course, he avoided me entirely while others laughed and waved; as if we'd shared an intimacy far beyond what we had in deed.  That was when I realized the magnitude of my error.

Later I crafted fictions to forgive myself.  I wanted him to see that he could ask a small favor and have it granted.  I wanted to show him the possibilities that remained for human touch.  He needed it.  But all those were rationalizations.  True in ways perhaps, but at bottom I wanted to do it, wanted to pull close this scrawny middle-aged heroin junkie, this wasted scrap of human potential and make him feel warmed, supported, loved.  Why him and not others, I don't know.  Probably just because he had once been handsome, and because he spoke with such measured dignity and cocked his head so attentively to one's words.  Difficult to explain, of course.  Of course.

the dogs of war

What a vast wreckage of human potential this senseless, endless war has brought.  These boys must have been so sturdy and shining, all big grins and lanky muscles; elan and eagerness; brawn and bravado; going somewhere  Now they recount their grisly everydays in beaten voices, giving no special emphasis to the horrors that became as nauseatingly familiar to them as weak tepid OJ in the glaring Mideast morning.

Were I their mothers, how insatiable would be my fury.  To think these bland smirking suits had taken all the life in one's beaming child and ground it down to this.  And that the thought should cross any mother's mind how very lucky he was to be back at all, not to be the subject of someone else's horror story; how unspeakable that for this one should have to feel grateful.

These boys, I am nothing to them; and yet I would like to hold them to my chest and let their warm hot tears flow over us both, let them crawl back into a time when horror movies were just a bit of fun and the thought of war exciting, nothing more.

Tuesday, May 27, 2008

it could happen to you

Mr G, a gentleman in his sixties with an engaging manner and a professional degree, had never set foot in a psychiatric unit until today.  Bald and avuncular, with a rich white beard and a mischievous wink, he had a bit of a drinking problem and some deep-buried scars from his time in Vietnam.  But nothing else really, none of the 'meat' of inpatient psychiatry (schizophrenia, schizoaffective, bipolar disorder) that we spend our time handling.

Someone somewhere thought two antidepressants and some Antabuse would be good for him.  In a week or two he had changed his personality entirely, wandered into moving traffic, threatened the police who came to the scene, and attempted to seduce the psychiatry resident who admitted him - nothing anyone who knew him could have believed.  Indeed his family members called daily, frantic for understanding, unable to comprehend how their loved one had been replaced by a stranger.  In short, he had had a manic and psychotic episode.

But what is 'psychotic,' other than a term used loosely by the ignorant to describe the behavior of those who irritate them?  Psychosis is a mental state characterized by the impairment of reality testing.  Any society typically has a consensus about what is 'real' and what isn't.  (Judgements about this may differ between societies, but that's a different treatise.)  People suffering from psychosis have fallen off this bandwagon and have very different ideas about what is 'real' from the man on the street.  But there's a method to the madness: psychosis typically involves several specific, bizarre modes of thought. Auditory hallucinations (usually voices), delusions (fixed false beliefs), and paranoia (the pervasive and unshakable feeling that unknowable dangers lurk) are hallmarks of the syndrome.  Though each patient is unique, themes quickly emerge, and anyone who has spent more than a week or two on an inpatient psychiatric unit will begin to recognize the patterns.

Psychosis, clearly, is not a torture reserved for the unlucky few born to its ravages, like cystic fibrosis or a Thalidomide deformity.  I suspect it may be an alternative mode of function that lies buried in each of us, more deeply for some than for others.  It can be precipitated in otherwise mentally healthy people by pregnancy, medical illness, or - as in Mr G's case - merely the wrong combination of medications.  An unlucky few have the problem of chronic or recurrent psychosis.  This is the disease schizophrenia, a disorder with its peak onset in the normally promising and productive years of early adulthood.

Some are doubtless more susceptible than others; as with every human trait, psychotic tendencies lie along a continuum.  Mr G had always been a bit up-and-down in his moods, and while another person might have been able to tolerate the double-antidepressant regimen, for Mr G it magnified his normal highs and lows into an off-the-charts manic spike that came, as extreme mood disorders sometimes can, with the booster benefit of psychotic symptoms.

But what is this psychosis then, what is it for?  Why does its potential lie buried somewhere in so many of us?  What purpose does it serve?  Some have argued that it is a byproduct of the development of social complexity in the human brain  (see for example, Burns JK).
Unfortunately, this particular argument (and related ones) suffer from a lack of specificity and a paucity of evidence.  They certainly sound reasonable; but the logic boils down to this: Schizophrenia is a complex behavioral disorder - social and creative endeavors require complex processing and behavior - schizophrenics have difficulty with social functioning - ergo, these modules are related.

I don't doubt that schizophrenia (and psychosis more generally) are related to social functioning, given how important social functioning is to humans - almost everything we think or do is related to social functioning, broadly defined.  But that makes the hypothesis that 'schizophrenia is related to social functioning' so broad as to be useless. 
Another line of reasoning jumps off the intriguing finding that artistic inclinations and schizophrenia are often found in the same families (see Horrobin DF), and posits that schizophrenia is merely the other face of the coin of creativity.   This one is slightly more specific (creativity being less of a blanket term than 'social function') and can claim at least some circumstantial evidence to its credit.  

Dr Horrobin also does a nice job of suggesting a biochemical basis, though I am in general skeptical of papers that claim to pinpoint individual biochemical factors or pathways as causative of psychiatric diseases.  Psychiatric illnesses are complex states of the person as a whole, and doubtless they affect and are affected by many, many biochemical pathways (most of which, as we are discovering, interact with each other anyway).  Generally I'd say that trying to pinpoint a single gene, factor, or pathway in the pathogenesis of psychiatric disease is sort of like blaming global warming on a carbon dioxide spike in Juneau in the summer of 1998.  Sure, they're related; but there are a bunch of other factors involved, and who knows which way the causal arrow goes anyway.

In any case, those optimistic scientists who have persisted in trying to pinpoint single specific causes of psychiatric diseases are indeed finding out that the problem is significantly larger than one might have guessed back in the flushed and heady days of the one-disease-one-gene school of thought (Iwamoto and Kato).

I don't doubt that we'll make some interesting progress on this problem once as we develop better tools to manage and investigate complexity in biology.  The ever-growing computational power that's available to us makes it feasible to look at complex interactions in a way that was impossible twenty years ago.  It's going to be an interesting next couple of decades.

truth to power

The unspoken derives its power from its very mystery.  To make explicit is to deprive of power. The psychotic patient knows this, perhaps better than we.  Psychotic patients often seem in touch with a deeper, animal reason.

Mr. B. behaved like nothing so much as a cornered animal in the locked psychiatric unit.  Behind closed doors, he admitted his demons to his worried mother, who relayed them to us; but to the doctors he was close-lipped and angry, hiding with insults his fear at what had happened to him.

His threatening, hostile stare fairly made the air vibrate in the room... yet the moment the attending asked of him, frankly and without guile, "Why are you staring at me?" the spell collapsed, deprived of all its power.
"I'm not staring at you," was his only, weak recourse.
But it was nothing so simple as her bare words that disarmed him.  I pictured the same patient on a gritty street corner, leveling his rapier gaze at a fellow thug.  The same phrase spoken in an equally hostile tone by a burly, puff-jacketed swaggart would have but escalated the situation.  It is the opt-out, the calm inquiry, the untroubled curiosity, that undercuts the threat.

Good therapists wield this tool with skill and precision.  They refuse to play the game, choosing rather to analyze it.  All of us, as humans, have some understanding of this complex social game.  We approach and retreat, feint and parry, dance an endless dance of human relations - all without a word, a world of interactions parallel to but separate from our explicit verbal exchanges.

People who play the game well become leaders, extracting what they wish from others while retaining their loyalty and affection.  People who have a shallow or incomplete understanding of it become recluses, frustrated at every turn by interactions that go awry.

But whether they play it well or poorly, in the normal course of human behavior the game is never made explicit.  To make it explicit is to undermine it entirely.  The therapist does this in a controlled manner, slicing the game out of its skin and dissecting it apart, displaying its innards openly to his patient's wonder and, perhaps, dismay.