I’m not a huge fan of books. They tend to be overly narrative and sculpt information in a fashion which supports a conceit rather than explore context. Of course, this is probably what most people expect from books and this is just my square-pegness (I think autocorrect went into convulsions over that one) manifesting.
Books are valuable though and learning how to express things narratively is a skill that definitely needs work, so it’s time to massively ingest a series of patterns to synthesize a coherent style that is more compatible with other people’s expectations.
Will try to do these at least once a week, and any feedback, suggestions, and commentary are welcome.
I probably should have read the book first before picking it based on the title and synopsis alone, but from a psychiatry perspective, this feels like the closest I’ve ever seen to accurately understanding the mechanics of how nervous systems function. Will update as I go, still trying to figure out formatting. Usually I edit as I go since it takes a few hours to read a book, but that gets confusion so I need to think about how these should look.
Edit: Review – Live Blurbing
Wow, that dedication is the least cheesy, most real dedication I think I’ve ever read in a book. Most people enter medicine adjacent sciences with the belief that they are going to “save” themselves or someone close to them. Almost always however, we are improving the world for people we will never meet, likely beyond the lifespan of the people we hope to “cure” (including ourselves).
Introduction: “Schizoeffective Disorder” is probably a type of “Asperger’s Syndrome”. Heh, this guy has a shocking amount of self awareness for a psychiatrist. Hoping later in the book he makes the jump concept of “mental illness” being flawed, rather than being frustrated by the ineffectiveness of existing treatments. And just like that, it appears this is a keto diet book. Sigh. Haha, and the very next sentence tells me I’m wrong. Well played.
That was a wild introduction, reminds me of that “Had me in the first half” meme. Got really concerned about the keto diet but the follow up not only killed my expectations, but did a great job of setting new ones.
Chapter 1: Heh, shit’s fucked up and shit. Advancing incidence and prevalence rates is something I’ve been personally really concerned with, especially with regard to dementia. It’s such a hard thing to really square with psychiatry as a whole, that the more psychiatry we apply to psychiatric problems, the worse these psychiatric problems are getting.
Chapter 2: So I’m gunna disagree with the “Major Depression is Well Defined” argument here, or counter it with “If MDD is the most well defined, then our definitions are unrecoverable shit.” Inter rater reliability for this is awful, and when we stop cheating and the more raters we use in our study, the worse it gets. I love how every single “risk factor” for MDD is more aptly described as “adverse life conditions”.
Huh, I’ve never seen “learned helplessness” as a concept. Lol, (paraphrasing) “antidepressants work for some of the people some of the time” pretty much sums up medicine. He’s doing a pretty good job of setting up how scattershot treatment is. Symptoms vs. cause is a REALLY important distinction, especially with regard to treatment.
Wow, he actually explains “correlation does not equal causation” (vomit emoji). This phrase is so absurdly abused that it’s largely lost it’s meaning. He does a good job of explaining that correlation by itself generally means fuck all.
SORE THROAT DISORDER DUE TO TYLENOL DEFICIENCY. Oh my god, the rest of this book could be utter trash but that alone (well and everything else so far) gets a gold star.
Chapter 3: Shitting on the DSM is such low hanging fruit, but I’m here for it.
Researchers have been trying for decades to figure out what makes individual disorders different from each other at a biological level. Interestingly, they don’t yet have any clear answers.
And thus… the remodeled brain is born. This chapter is ultimately the heart of it, if these “treatments” are supposed to work.. why don’t they work? As an aside, it’s a little weird how many of these cited studies I’ve read. There’s just so much out there it makes me wonder if this isn’t just a case of similar selective biases rather than being a good summation of the evidence.
Chapter 4: It’s still a bit weird to me that a question like “Could it all be related” is controversial at all, and shows just how stuck we are behind philosophical constructs of function. Of course it’s all related, and until we start seeing physics understandings get broken in nervous systems it’s literally impossible for it NOT to be all related. But here we are.
Heh, from “autism” to epilepsy to dementia, feels like a page out of my brain. This book is confirmation bias porn, the only thing missing compared to this forum is an exploration of how the metabolic processes actually work.
Chapter 5:
Creating a new theory is not like destroying an old barn and erecting a skyscraper in its place. It is rather like climbing a mountain, gaining new and wider views, discovering unexpected connections between our starting point and its rich environment. But the point from which we started out still exists and can be seen, although it appears smaller and forms a tiny part of our broad view gained by the mastery of the obstacles on our adventurous way up.
NICE. A theory that is not consistent with existing data is garbage. Not some of the data. All of the data. Even bad data should be reconcilable when the issues are rectified.
The first significant misstep, “energy imbalances”. Psychiatric background couldn’t escape the whole “defective person” allure I guess. Damn, and then followed up with factual issues.
On top of that, there are an additional ten to fifty glial cells per neuron.
The ratio between glial and neuronal cells is actually closer ~ 1.1:1 in human brains, and declines from there depending on the animal.
He has the right idea just has bad biology throughout this chapter. Damn, there’s a lot of right for the wrong reasons here. The scope of metabolism being presented ends up in the right place, but there’s a lot of misunderstandings about the underlying biology. Come to think of it, the actual biology is where most of these types of conceit go awry. And from my observation, most biologists don’t like to touch this stuff at all. Interesting. The summary jumps ahead a bit, while it is true that metabolism is part of the definition of life, I didn’t see that being established in the text.
Chapter 6: Okay, so I largely agree with a lot of the things so far in this chapter, but don’t believe it was supported well enough in the book (most likely because the body of evidence isn’t quite there yet to support it). There’s also a pretty big gap in explaining how single events permanently change metabolics, or the variance between “adverse” environment and outcomes.
Psychiatry tends to dance really hard around environmental/”social” etiologies and this so far isn’t much different. The environments that children experiencing ACEs in tend to be persistently “externally” harmful, rather than ACEs in and of themselves causing metabolic issues. It’s not the ACE itself, but the social environment itself adding additional harm after the fact. Further, why isn’t “I didn’t get an Xbox for Christmas” an ACE? That’s pretty damn devastating for some kids.
Oh RDoC, what you could have been. It’s a damn crime that we aren’t drawing up plans for Rev 3 by now, instead of just now dribbling out a study or two under the original criteria (which honestly aren’t very good). I didn’t find the car/pain examples particularly compelling.
And we have our first NOPE moment in the offered definition of mental disorders requiring brains to be “not working properly”. Especially in the context of “disorders” like “autism”, “ADHD”, or “OCD”, where the brains are almost certainly working exactly like they are supposed to, but experiencing social harm because of it.
Yeah, this is back to the psychiatric “Something wrong with the individual” vs. the more appropriate “sociality is fucked up and shit”. You can’t take the psychiatrist out of the person I guess. Damnit, things were going so well too.
Ugh, starting the passage saying “well we can’t measure this accurately”, then immediately saying “OCD is caused by this specific thing we can easily measure accurately” is a little on the nose dumb (not to mention it’s poorly supported by the evidence). Stuff like “ADHD” is caused by an underactive brain region is honestly representative of the worst of psychiatric etiology work.
Heh, he mentioned glia once (the cells that control metabolism in brains) and hasn’t mentioned them again. Two chapters in and it’s all neurons. Sigh. His “Underactive/Overactive/Absent” is a bayesian rehash, and bayesian mechanics are magical in that they can be used to approximate any state because they include every state.
Yeah, no this is just more “person” blaming. The core psychiatric concept that people who aren’t resilient to societies bullshit are somehow defective underlies the fundamental awfulness of current psychiatric practice.
Chapter 7: So, mitochondria do control a significant amount of aerobic metabolism, but humans (and nearly all organisms on earth) also have a core anaerobic process. Mitos are translators, not necessarily the controllers of metabolism.
This origin of mitochondrion isn’t really supported by the evidence any longer. This type of view usually arises from a “DNA first” perspective, rather than “RNA first” perspective. While there’s a significant chance there was a precursor state to RNA world, this explanation doesn’t really track.
Heh, talking about Ca2 without talking about astrocytes should earn you a slap on the wrist with a ruler. Eh, damn. This chapter is the epitome of why I dislike books, the authors get stuck on a conceit and start doing mental gymnastics to support the concept rather than really exploring the concept.
Chapter 8: I wonder if the pattern in books is to stuff all the uncontroversial, well explored concepts in the front as an inducement to the more controversial stuff?
Another chapter of “We can totally measure all these defects in function with all these amazing tools!”, followed by an absence of discussion about why clinical validity of these supposed biomarkers is so shit. More “It’s hard to measure!” followed by “we can totally measure this thing and get our answer!”. And absolutely zero discussion about why all of that stuff useless without longitudinal testing since every single measure would be relative to the individual (or their genetics). Even an argument like “relative to expected values based on genetics” would work here, but no, MRI is magic again.
How do you have a whole ass passage on how correlation does not equal causation and then spend the rest of your book trying to do exactly that? What the fuck?
Again, just like glia, how is it even possible to talk about mitochondria this extensively without talking about RNA?
Now we are listing all the correlations with specific biomarkers (after starting the book talking about the heterogeneous morass of biomarkers). It’s almost grotesque to spend multiple paragraphs talking about the predictive ability of “ALC” without following up with why it doesn’t predict shit in the real world. It’s even worse to talk about conditions like “MDD” and “Bipolar Disorder” as if they are genetically determined conditions instead of being based on arbitrary ass criteria. Like they literally opened in the “shitting on the DSM” chapter talking about how the symptom list is a fucking pick list, but now they are solid enough to build genetic correlations from. Can’t take the psychiatrist out of the psychiatrist I guess.
This section about the link between UTIs and dementia is a good example of ignoring psychiatry’s warts. ANTICHOLINERGICS, the medications which we would used to treat incontinence or other urinary “conditions” CAUSE (yes, using cause here) dementia in high enough dosages. This is so well known that we actually have a warning scale called the “Anti-cholinergic Burden” scale. Guess what the primary MoA for most psychiatric drugs is?
Chapter 9: Causes of these problems: You are fucked up. Not a cause of the problem: Your environment is fucked up. Any questions?
This was a weirdly short chapter.
Chapter 10: Lol, the old GWAS can’t find any concrete genetic bases, only associations, but our shitty picklist driven definitions can’t possibly be the problem argument. I think I mention APOE4 often, but do you know what the actual risk of “Alzheimer’s” from having multiple copies of APOE4 is? A few percent. It sounds scarier when we say “RISK GOES UP BY 25 TIMES”, but the actual effect size is actually ridiculously small.
I was going to try to be generous and say man, maybe all these DNA references really mean “RNA” underneath, then the author drops “factors like micro-RNAs (what’s the difference between any other type of RNA?)” and I’m lost again. At least we’re talking about RNA finally, especially since they are responsible for the whole constructing the proteins necessary for signalling thing.
Epigenetics as a whole is one of those topics that makes me break out into a cold sweat because it inevitably is used as an excuse for why the models don’t work.
Chapter 11: Yay, chemical imbalance theory. The author feels it’s important to note that his framework doesn’t challenge it at all. Can’t take the psychiatrist out I guess.
Neurotransmitters are not just simple on/off signals between cells.
Lol, that’s exactly what they are. Well, maybe it’s more appropriate to say that neurotransmitters provide valence/weight to intercellular interactions, even if the actual data itself is underlying peptide/proteins. They are like a faucet which control how much water come through a hose.
For example, SSRIs are likely working by increasing mitochondrial biogenesis and improving the function of mitochondria. This process takes time; it doesn’t occur overnight, even though SSRIs increase serotonin in a matter of hours.
UHHHHHHH. AND AGAIN, we start the book by talking about how amazingly responsive mitochondria are, but somehow these drugs are slow because mito changes take time?
This success story is wild. They were blowing out this 81 year old’s ACB with multiple anti-cholinergics, and his amazing success story was suggesting less be prescribed. That’s psychiatry.
Chapter 12: It occurs to me that the focus on DNA vs. RNA and neurons vs. glia are probably born of the same type of stubborn assumption driven thought that simultaneously insists it knows exactly how things work but asserts it has no idea how things work.
My biggest fear reading this book is that I’m going to go over these references and the effect sizes are going to be absolutely garbage. Like “.1% of MDD diagnosis meets this phenotype” kind of garbage, followed up by inconsistent or non-existent replication. The last few chapters have had me begging the author to go back and read their “correlation does not equal causation” bit because that shit is out of the window now. It’s like it got the old Russian defenestration as soon as it became inconvenient.
Yep, saw this coming. “Mental Disorders” are mostly caused by insulin resistance. Pack it up boys, we got it solved.
“Pre-menstrual dysphoric disorder”. That’s right ladies, hard periods are a mental disorder. I fucking love psychiatry.
Success story time again! A 54 year old man diagnosed and “treated” for bipolar disorder for THIRTY YEARS was resolved by blasting out his cholinergic balance until ten years later when he was at risk of (or experienced) arrythmias and osteoporosis, at which point his internal function had degraded enough they could titrate down the dosage. This cured the depression! And that resolved the mania also. And that resolved the mania as also[Anakin]?
Chapter 13: Do microglia cause inflammation? I’m pretty sure they react to inflammation but I need to double check that. But hey, at least we are talking about one of the types of glia again. High levels of inflammation cause people to become lethargic, withdrawn, and unmotivated. Inflammation also causes dementia patients to become irritable and actively combative. Okay. If the author had been more subtle about this, with a couching statement like “inflammation has different effects on different people” we’d be cool, but no. And we resolved this with anti-inflammatories or steroids right? Of fucking course not. Because brains are magical and work different than other cells because they are in the brain.
Chapter 14: Ahh, the old SCN light related zeitbergers control metabolism conceit. Because something to do with neurons. Sigh. Pre-industrial high latitude societies are a shambles.
Another success story, bright light therapy cures a distressed teen going through significant metabolic/developmental changes (also called PUBERTY). Kaleb got even better when COVID hit and his fat ass wasn’t subjected to school bullying anymore! Fucking hell. It’s genuinely awesome his life improved, but holy shit the author even has to write that it doesn’t work for most people, but it worked for him.
Actually I need to step back for a moment and say it’s great that the author is at least willing to try new things with patients instead of aggressively adhering to their training. That’s genuinely impressive. Despite my skepticism, we could improve outcomes for people just by showing a willingness to do something different instead of sticking to the same class of “treatments” regardless of the result. If the author was even slightly more skeptical of psychiatry as a whole, they’d probably find their effectiveness significantly improved, even beyond the level that they feel they’ve achieved.
Chapter 15: Eat right, don’t be fat, don’t get mental disorders. Got it. Sigh. In this chapter, the author pretty much goes full nootropics. But more important than that, don’t be a fatty. Even Schizophrenia can be cured sometimes just by not being a fatty, even if the schizophrenia existed before being a fatty. Even if you are treated for schizophrenia for checks notes 50+ years (holy fucking shit) and no one gave a second thought about your weight (or you personally, rather than your “symptoms”).
Chapter 16: And finally, I had a feeling this was coming. Drugs and alcohol bad kids. Weed is CAUSAL to SCHIZOPHRENIA. It’s like we got teleported back to 1995 drug policy research land. Maybe MDMA still causes big scoops to disappear from people’s brains. Alcohol causes disorders, except for the 99.995% of people it doesn’t. I wonder if the author is really going to go for it and mention Fetal Alcohol Syndrome, a syndrome which has ZERO association with alcohol use. Place yer bets.
Drugs and alcohol are damaging and addictive, but the drugs we prescribe somehow aren’t. We wouldn’t want to admit to committing malpractice on a mass scale, so alcohol causes withdrawal, SSRI’s can maybe possibly occasionally not much research to support that they result in “discontinuation effects”.
And the bottom of the barrel “evidence” here, holy shit. Adolescent rats were subjected to nearly lethal amounts of a substance and even over the short term it didn’t go well! By the way, keto “helps” with alcohol detox, but if you drink while on keto it may kill you. Holy christmas.
HOLY SHIT! Our first mention of astrocytes in relation to… marijuana. Oh well, at least it’s in the record. Hopefully we will eventually get a few other types of glia in the next few chapters. It’s interesting that the author quotes a study that literally implies astrocytes control neuronal metabolism, but this is the first time in a book about metabolism that it’s come up. Wow.
By the way, the sticky icky causes “memory impairment” due to a genetically expressed receptor. If we delete the receptor in mice, no “impairment”. What does this mean? Absolutely nothing except our genes know what the devil’s lettuce is and have developed a robust genetic expression to accommodate it.
Chapter 17: Ahh exercise. Yeah, it doesn’t actually help with “mental disorders”, but that’s probably because of diet or other drugs. Not the kind of drugs that psychiatrists like me prescribe mind you, but the bad ones like alcohol or happy little trees. Elite athletes greater incidence and prevalence of mental disorders compared to non elite athletes must have something to do with all the drugs they use in between being aggressively drug tested. Or something.
I understand why this chapter was buried so deep in the book, it’s a huge thumb in the eye for the “imbalance” construct.
Chapter 18: I thought this chapter was going to be about social inputs, but no, it’s about why “autists” (and other conditions) are defective. Fuck this guy. This whole chapter is really bad. I’m annoyed now, lol. Find god, find your purpose in life, and your mitochondria are good. We can also maybe drug your mitochondria (or shine bright light in your eyes) and that might the equivalent? This is just an inconsistent mess.
Success story, Sarah cured her ADHD and anxiety by finding a job which didn’t require anything challenging from her! Good going Sarah!
Chapter 19: Why do current treatments work? THEY FUCKING DONT. That’s why incidence and prevalence is rising. You spent an entire chapter dunking on the status quo over this. The author literally notes “Most of these conditions cure themselves with time!” in that discussion.
ECT is the GOLD STANDARD for treatment resistant depression and catatonia? Since when? There’s a reason that despite all the negative associations with MDD that ECT is such a last ditch kind of treatment. And since when is ECT better than Benzos for catatonia? Does gold standard mean something different than I’m thinking it does?
Chapter 20: Oh man…
When a flower doesn’t bloom, you fix the environment in which it grows, not the flower.
The complete lack of awareness in including this quote is amazing. AWESOME quote. What the hell does it have to do with this book, which is ENTIRELY about changing the person rather than the environment?
This chapter, about how to build a treatment plan, starts us off with the most amazing bit of advice that no one would ever consider… trust a clinician. The clinicians that he’s writing a book to help understand how to treat these things because they are fucking it up.
The next step is to try an inpatient or residential program. The same programs that have a demonstrably deletory effect on outcomes. And not even by a small margin either, literally doing nothing (you know, because these symptoms “fix themselves” in most cases) results in better outcomes. And that’s it. Beth got therapy and was cured. Of her “genetic” condition. I’m overly simplifying… but kinda not?
Chapter 21: Sigh. So here’s the problem with this chapter and the book as a whole, the author is so locked in on “mitochondria” that they blew right past really understanding how “metabolism” works or what it actually means. Honestly, the revolution that has been offered in this book literally doesn’t challenge anything, and explicitly states it doesn’t challenge anything, it just gives us different language to talk about these things. It’s so terrified of offending other psychiatrists (or challenging their own beliefs or core values) that it offers the same but different instead of any practical examination of these mechanics.
The absolute worst sin though is that it still is focused the idea despite the rising prevalence and incidence of all of these conditions, it’s that individuals are broken and need to fix themselves while completely ignoring toxicity of implying people are genetically defective.
Addendum: Will go over the references in later chapters in a bit.