Dr. Matthew Dumont treated a 44 year old woman with depression, body dysmorphia, and psychosis. She failed to respond to most of the ordinary treatments, failed to respond to electroconvulsive therapy, and seemed generally untreatable until she mentioned offhandedly that she spent evenings cleaning up after her husband’s half-baked attempts to scrape lead paint off the walls. Blood tests revealed elevated lead levels, the doctor convinced her to be more careful about lead exposure, and even though that didn’t make the depression any better, at least it was a moral victory.

The story continues: Dr. Dumont investigated lead more generally, found that a lot of his most severely affected patients had high lead levels, discovered that his town had a giant, poorly-maintained lead bridge that was making everyone sick, and – well, the rest stops being story about psychiatry and turns into a (barely believable, outrageous) story about politics. Read the whole thing on Siderea’s blog.

Siderea continues by asking: why don’t psychiatrists regularly test for lead?

Now, in my case, I’m a talk therapist, and worrying about patients maybe being poisoned is not even supposed to be on my radar. I’m supposed to trust the MDs to handle it. Dumont, however, is just such an MD. And that this was a clinical possibility was almost entirely ignored by his training. Dumont’s point here is that while “medical science” knows about the psychiatric effects of lead poisoning and carbon disulfide poisoning and other poisons that have psychiatric effects – as evidenced by his quoting from the scientific literature – psychiatry as practiced in the hospitals and clinics behaves as if it knows no such thing. Dumont is arguing that, in fact, he knew no such thing, because his professional training as a psychiatrist did not include it as a fact, or even as a possibility of a fact. Dumont’s point is that psychiatry, as a practical, clinical branch of medicine, has acted, collectively, as if poisoning is just not a medical problem that comes up in psychiatry. Psychiatry generally did not consider poisoning, whether by lead or any other noxious substance, as a clinical explanation for psychiatric conditions. By which I mean, that when a patient presented with the sorts of symptoms he described, the question was simply never asked, is the patient being poisoned? Dumont wants you to be shocked and horrified by what was done to those people, yes. He also wants you to be shocked and horrified by this: psychiatry as a profession – in the 1970s, when (I believe) the incidents he relates where happening, in the 1990s, when he wrote it in his book, or in 2000 when a journal on public health decided to publish it – psychiatry as a profession did not ask the question is the patient being poisoned? And it didn’t ask the question, because clinical psychiatry had other explanations it liked better, to which it had a priori philosophical commitments. And that, when you think through what it means for psychiatry, is absolutely chilling.

And:

I can tell you that, standing here in 2018: • No mental health clinic I’ve worked at ever had the facilities for even performing blood draws, nor doing urine testing for anything other than commonly abused intoxicants (alcohol, opioids, amphetamines, etc), and then only the clinics that specialized in substance abuse treatment. The clinic I work for now can’t even do urine screens. Psychiatrists’ offices, here abouts at least, are not places blood tests are or can be performed, unless they are attached to a general medical practice. Such tests have to be referred out, usually to the patient’s PCP’s office. • No psychiatrist has ever asked me to arrange blood draw test from the PCP for anything other than white blood cell count, thyroid panel, or Lithium blood level. • Though I’ve seen documentation in patient charts of psychiatrists ordering two of those three tests from PCPs themselves, I’ve never seen documentation of ordering any other tests. I have literally never seen a psychiatrist order a test for any sort of poison. • I have never seen any sort of toxicology report for poisons in any of the blood test results I have found in my patients’ discharge paperwork from psychiatric hospitalization. • I have never, in all my case discussions with psychiatrists in-patient and out, or with hospital staff at psychiatric hospitals and hospital departments, ever heard anyone suggest anything about poisoning be a possibility in our mutual cases. Nobody has ever said anything like, “We don’t want to prescribe anything until the tox report comes back, in case it’s an environmental toxin” or “R/o env tox” or even “We don’t think there’s much chance of an environmental toxin, so we’re not bothering to test for it. It has literally never been mentioned. • Not even when, due to the suddenness of the onset of psychotic symptoms, psychiatrists were discussing with me the possibility that a patient was intoxicated on some street drug that somehow just wasn’t showing up in his/her urine screens and blood draws. Maybe it’s not fair for me to generalize from the psychiatrists I’ve worked with. Maybe it’s just that the psychiatrists I’ve worked with – including at MGH and McLean – aren’t representative, being somehow really bad doctors, or poorly educated, and that, contrariwise, normal psychiatrists, basically adequately well-trained psychiatrists, generally do stop to consider poisoning as a cause for severe presenting symptoms, especially when they’ve proved refractory. I’m not getting that impression though. I’m not getting that impression from the many interactions I’ve had with psychiatrists and other psychiatric professionals over the last decade, and neither have I been subject to exhortations of what I, as a clinical mental health counselor, should be alert to as evidence of possible poisoning in my patients. When I was in grad school, it was briefly mentioned that most disorders in the DSM (this was version IV-tr) had a “caused by a General Medical Condition” variety, and then it was never spoken of again. So as far as I can tell, nothing has changed. This is not merely an incidental failure of instruction on the part of Dumont’s med school professors, nor of mine in grad school. This is, at the most charitable, a massive blindspot, of precisely the sort that “scientific” field of endeavor should never have, and it seems to afflict the entire profession.

There’s a lot more, and you should read the whole post. Siderea is a great writer and a careful thinker, so when she criticizes my practice I take note. And since I don’t think I’ve ever tested anyone for lead, this is definitely criticizing my practice. What’s my justification?

Take a look at some papers like The Emerging Role For Zinc In Depression And Psychosis and Effect Of Zinc Supplementation In Patients With Major Depression: A Randomized Controlled Trial. Done? Looks like there’s some pretty good evidence that zinc deficiency is involved in depression somehow, right? Do you think zinc is more or less important than lead? By how much?

Or what about toxoplasma? Seems to be twice as common in depressed people as in controls, and increases suicide risk 50%. Pretty suspicious; should we test all depressed people for toxoplasma? If so, is this more or less important than testing all depressed people for lead? By how much?

And when you’ve answered that, what about copper? Omega-3/omega-6 ratio? Vitamin D levels? Cortisol? Magnesium balance? The methylation cycle? Mitochondrial function? Inflammation? Covert viral infections? Covert autoimmune disorders? Paraneoplastic syndromes? Allergies? Light exposure? Circadian rhythm? Selenium? Lithium levels in your local water supply? Insulin resistance? Gut microbiome? PANDAS? FODMAPs? Structural brain abnormalities? And that’s not even getting into the psychosocial stuff!

Every one of these has some evidence of being involved in depression. Some have excellent evidence of being robustly involved. Imagine how dumb you would feel if it turned out only 0.01% of cases of depression were lead related, and you spent so much time testing your patient for lead that you never got around to asking about color temperature of their home lighting, or whether they clean their cats’ litterbox, or how many dental fillings they have.

(Dental fillings? Really? No, not really.)

Why not test all the things? Number one, cost. Number two, sticking your patient with more needles than a Trump voodoo doll owned by the DNC. But number three, everybody is weird in a bunch of ways. Have you ever gone to your doctor for labwork, and gotten a piece of paper back with a lot of words like BASOPHILS and BUN-CREATININE RATIO, and probably three or four of them were highlighted in red to indicate they were abnormal, and your doctor looked at it and shrugged and said not to worry about it? That’s because everybody is weird in a bunch of ways. Your 30-item depression risk factor panel is going to come back saying you don’t have enough selenium and your gut microbiome is off, and your doctor is going to make you spend a month eating nothing but kefir and brazil nuts, and then a month later you’ll leave your abusive partner and your depression will mysteriously disappear.

Consider prostate cancer screening. This is like the best-case scenario for universal testing. Prostate cancer is pretty common – about 10% of men are diagnosed with it sometime during their lives. We know who’s most at risk – older men. It’s potentially pretty bad – nobody wants cancer. The test is easy – the same simple blood draw that tells you if your cholesterol is too high. And yet governing bodies keep recommending that doctors stop screening for prostate cancer (recent guidelines are nevertheless complicated: ask your doctor if PSA screening is right for you). The bodies cite possibility of “overdiagnosis and overtreatment”, potential false security by missing some cancers, and studies which show no decrease in mortality. Breast cancer screening organizations keep pushing back the age at which they recommend women start getting mammograms, because the costs outweigh the benefits before then.

Doctors never just say “I hear this condition is bad in my field, let’s worry about it with everyone who comes through the door”. They want really good evidence that it’s common enough (and that testing works well enough) that the benefits are worth the risk. Right now for lead, we have no such evidence.

The only study I have ever seen even begin to make the slightest attempt to quantify the role of lead in depression is Bouchard et al. It claims that people in the highest quintile (top 20 percentiles) of lead exposure have twice the depression risk as people in the lowest quintile. Big if true. But I’m skeptical, for several reasons:

1. Lead exposure is heavily linked to poverty – poor people tend to live in the decaying houses and polluted neighborhoods where lead is most common. Poor people are also more likely to get depressed. The study attempted to control for poverty, but this never works. So it’s not clear how much of the lead effect they picked up was really a poverty effect.

2. This is an implausibly large effect size. The amount of environmental lead has plummeted over the past thirty years after the removal of leaded gasoline. Since then, the percent of people with elevated lead levels has decreased by a factor of twenty. Some quick calculations suggest that if this study were right, depression rates should have gone down 66% in the past few years. They haven’t. Compare this to violent crime, which we have better evidence is lead-related and which did decrease by a factor of 2 or 3 over the past few years.

3. I don’t entirely understand what they’re doing with statistics here. In Table 2, every lead quintile has about the same depression rate. It’s only after they apply their model that they find higher-lead people have higher depression. This is sort of a red flag for the kind of thing that might not replicate later on. Nobody else has ever tried to repeat this study and as far as I know it remains the only investigation into the epidemiology of lead and depression.

Aside from this study, we have nothing to guide us. Does lead contribute to 5% of cases of depression? 0.5%? 0.0005%? I’m not sure anyone knows.

If it’s 0.0005%, then we’re talking about people who work in lead mines, or Dumont’s patient who scrapes lead paint off the wall every day. I agree if your patient works in a lead mine and has any problems at all, you should test them for lead poisoning. This is why your doctor asks you what line of work you’re in when you go in for an evaluation. She’s not trying to make small talk – she’s waiting for the one guy who says “I French kiss cockatiels for a living” so she can diagnose him with psittacosis.

I am definitely not going to make every patient take a blood test just so I can catch 0.0005% of people. But should I be more careful in the history here? Specifically ask patients “Do you have any hobbies that put you in contact with lead?”. I’m not sure – right now I have no intuition for whether that’s more or less important than “Do you do anything that might cause zinc deficiency?” or “Do you clean out cat litterboxes?” Usually what I do is I ask broad open-ended questions to start with, and then as the depression proves itself weirder and more treatment-resistant, we gradually go one-by-one down the list of super-rare causes that never happen in real life so I can be sure I’m not missing anything.

What if lead causes more like 5% of depressions? In this case, we’re talking about people with no specific exposure factors. Maybe they just live in an old house, or a bad neighborhood, or got a bad draw in the genetic lottery for whatever systems affect heavy metal removal. So suppose I grudgingly give every patient who comes through the door a blood lead level test. Lots of them come back with lead levels in the top quintile – just like 20% of the general population would. Now what? I say “Your lead level is within the normal range, I have no proof that it’s contributing to your depression at all, but just to be safe you should move to a classier neighborhood”? “Oh, you mean that will cure my depression?” “No, Dr. Dumont didn’t even cure his patient’s depression when he made her stop scraping lead paint off the walls, I’m just saying it probably couldn’t hurt”. I consider it a good day when I can get my patients to take their Lexapro without missing any doses. My ability to get them to move to a nicer neighborhood – most people aren’t living in bad neighborhoods just because they never thought of moving to a better one – is pretty low, especially when I can’t even honestly say I expect it to help that much.

What about chelation therapy, a series of techniques that suck lead out of the body? From Wikipedia: “Chelation therapy must be administered with care as it has a number of possible side effects, including death…various health organizations have confirmed that medical evidence does not support the effectiveness of chelation therapy for any purpose other than the treatment of heavy metal poisoning.” If you chelate everyone who comes through the door with high-average lead levels, there’s no guarantee you will cure any depressions, but you will definitely kill some people.

There’s an old medical maxim: never do any test if you have no plan for acting on the results. What’s my plan for acting on the results of a upper-end-of-normal lead level? I really don’t have one. If it’s an extreme level, the 0.0005% works-in-a-lead-mine type, then I can at least demand the patient find a different line of work. But if I’m just going to be diagnosing 20%+ of the patients who come in the door with upper-end-of-normal lead? Forget it.

I understand Siderea probably isn’t recommending universal blood lead screening. But then I’m having trouble figuring out what she is recommending doctors do differently. Ask everyone some history questions to see if they work in lead mines? We try to do that kind of thing already. Have lead poisoning on the top of our minds and ask a lot of really intense history questions to ferret out any possible exposure? Not clearly privileged above doing that for the thirty other rare causes of depression. Just make sure to talk about lead as a cause of depression in medical school? They already do, it’s right between “Prader-Willi Syndrome as cause of obesity” and “Q fever as cause of pneumonia” in the lecture series entitled Extremely Rare Causes Of Common Symptoms Which Ideally You Can Keep In Mind And Have Dr. House Levels Of Diagnostic Genius, But Let’s Be Honest Here, Realistically Over Half Of You Will Prescribe Antibiotics For Viral Infections.

I’m not saying nobody should worry about lead poisoning and depression. I’m just saying those people shouldn’t be front-line clinicians. Some epidemiologist should absolutely be trying to replicate Bouchard et al’s work on the magnitude of the lead-depression correlation. Some guideline-making body should be coming up with a guideline for when doctors should take lead levels, and what results should prompt what kind of action, even if the guideline is just “never worry about this unless somebody works at a lead mine” (which is plausibly the right answer given the current paucity of data, but I’d feel more comfortable if a guideline-making body said so officially). And public health officials should worry a lot about how to decrease lead on a society-wide level (which they’re already doing, albeit for different reasons), since that’s much higher-yield than some random doctor telling a poor person to move to a different house.

But I am not sure the average clinician needs to think about this too much.

(Maybe Siderea already agrees with me here; I can’t tell.)

There are thirty-plus plausible causes of depression that nobody knows enough about to be sure they’re real, estimate their magnitude, or begin to treat. If you look at any one of them too closely, you will come to the conclusion that every psychiatrist in the country is a quack who’s ignoring the evidence right in front of their eyes and willfully blind to the role of [lead/zinc/toxoplasmosis/inflammation/gut microbiome/etc] in order to keep getting the sweet pharma company cash for prescribing Lexapro. It’s not that we don’t know about these things. It’s that we don’t have an action plan. We don’t have a good feel for when to do the tests, what numbers on the tests mean we should do something, what that thing should be, and whether it should work. So we punt the question to the researchers, who already have a backlog of ten million other things they need to be working on.

This isn’t a great state of affairs. But I only know three ways doctors can deal with it, and none of them are very good.

The first is the one I learned at age 3 from my father teaching me to read out of evidence-based-medicine textbooks. You insist that nothing can be admitted into the medical canon unless it has some guideline-making-body’s stamp of approval, which the guideline-making-body will not give until a bunch of randomized controlled trials have validated every step of the model and shown that the proposed solutions definitely work on a large scale with every demographic of patient. Until then we will keep doing the things that have met that bar – which is basically giving people Lexapro and telling them to diet and exercise. This path assures you a long and prosperous career as a respected member of the medical establishment.

The second is to become Dr. Oz. You fall in love with anything that has an even slightly plausible mechanism and at least one n = 15 study saying it works. I’m not talking about literal homeopathy here. I’m talking about things where if you ask a biologist whether it works, they just sort of shrug and say “well, it should“, and there’s a bunch of respectable research into it. But this is a really low bar, and if it’s the only one you hold yourself to, then you’re going to be the guy telling your patients they need heavy metal tests and vitamin levels and SPECT brain scans and screens for twenty latent infections just because they came in saying they’re tired all the time. This path assures you a lucrative daytime TV show and a side gig selling supplements with your picture on them.

The third is to be a generally respectable doctor with one Big Idea. Like “why aren’t we testing everybody for lead?” or “why don’t we care more about the gut microbiome?”. These people are often really good at what they do, really passionate, and mostly within the mainstream. Sometimes they are impressive researcher-crusader-prophets, they get their Big Idea universally adopted, and then they become the next generation of medical orthodoxy. Other times they’re just annoying clinicians who love saying “I see you aren’t even testing for cortisol levels, clearly you have no interest in going beyond Textbook 101 Level” but can’t really explain why this is better than the twenty-nine other things you might consider doing. This path assures you a long bibliography of successful articles in The Journal Of Medical Hypotheses.

I love everybody in Group 3, they’re all great people. But the thing is, if I were to believe everybody in Group 3, then I would end up as Group 2 – and I don’t have enough time to star on a TV show, so screw that. I think that makes me Group 1 by default, which is good, because otherwise my family would disown me.

“Shouldn’t we be able to use rationality techniques to figure out which of the Group 3 people are right, and move faster than guideline-making bodies“? Well, that’s the dream. But take that route, and you notice you’re wading through ankle-deep skulls. I occasionally flirt with trying this – like every doctor, my practice has a few idiosyncrasies and places where it deviates from the exact textbook solutions. But I would be nervous putting too much trust in my own gut.

This is all context for how to think about questions like “should we test everybody for lead?” or “should we think more about lead?” or “is the psychiatric establishment incompetent for not testing lead more?” The prior on the psychiatric establishment being incompetent is never that low. But the prior on any given alternative being especially fruitful isn’t great either.

[EDIT: The only general medical conditions I consistently find worth worrying about in depression (absent some specific reason to worry about another) are hypothyroidism and sleep apnea. I test a lot of people for anemia and various vitamin deficiencies, because the guidelines say so, but I’ve never found them too helpful. Curious if anyone else in the field has different experiences. I recently had one patient obtain a miraculous and lasting cure of his chronic fatigue using nasal steroids (ie it was apparently caused by nasal inflammation from allergies) but nobody ever talks about that and I’m not sure if it was just a fluke.]