Oh and read Charles Nemeroff's work, he's a very naughty boy but a good scientist non-the-less and he's done a lot with cortisol since Bernard Carroll died, even though Bernard road him for years over the pharmaceutical payouts. Oh oh and Ian Brockington has some lectures up on YouTube talking about cycloid and bipolar in women. Oh and watch Nassir's lectures, he's too influenced by Akiskal and Kouk but he's got some good ideas.
You seem to be aware of the historical background of borderline, and your description of the psychopharmacological approaches is freakishly accurate.
I assume you've read Hannah Decker's book and know how borderline ended up in the DSM?
I assume you've read all of Edward Shorter's books?
I assume you're familiar with Hagop Akiskal's agony over borderline — his idea of “lamotrigine deficiency syndrome,” and how the diagnosis vexed him throughout his career?
I’m guessing you already know all of that.
But have you read Ian Brockington and Carlos Perris’s work on cycloid psychosis?
What about David Healy’s research on the women admitted to the Denbigh asylum in North Wales?
If you're anything like me, you probably followed the Kraepelin–Jules Angst–Robert Post–Akiskal–Koukopoulos–Baldessarini lineage — the Boston–Rome pathway. But there's another route, often overlooked: Angst’s research partner Carlos Perris followed a different trajectory, diving into WKL nosology. That path leads through Wernicke, Kleist, Leonhard, Fish, Perris, Brockington, and Bernard Carroll. The secret to the second path is that Perris and Brockington focused on peripartum and perimenstrual cases, and Carroll took this and focused on the endocrine system. The idea they had was that by examining de novo episodes of bipolar in the postpartum period, it might reveal a distinct phenotype, with discrete etiology and pathogenesis — or rather, you would at least know the etiology involves postpartum effects, thus ruling out a big chunk of other possibilities.
Both lineages have borne fruit in terms of treatment, and together they hint at something deeper: bipolar might actually consist of two distinct diseases — but not Bipolar I and II as we currently define them.
By now you've probably read about how David Dunner rushed the bipolar I/II split, and how he later regretted it. The real split might be between periodic illness and cycloid illness.
And this is where Bernard Carroll may have come close to solving the other half of the puzzle that Koukopoulos and Akiskal were chasing. For years, Akiskal, Koukopoulos, and Baldessarini were noticing a subset of patients who “switch” very suddenly, with more “mixity.” Carroll, meanwhile, was researching premenstrual tension — and I don’t mean “PMS” or “PMDD.” I mean tension — inner agitation, explosive rage, irritability — a distinct syndrome that separates out from PMS and PMDD.
Here’s the strange part: Carroll’s phenotype bears an uncanny resemblance to akathisia and the more extreme, volatile presentations of borderline. Think of the old “larval epilepsy” cases — what Falret and even Kraepelin thought might be post-ictal states. The big kicker though is that it also resembles these mixed switching types that Akiskal, Kouk and Ross were so interested in, the "irritable" ones.
Picking up on that thread, a few years ago Gabriel Sani tried treating PMDD with acetazolamide — with incredible results. I asked Alexia about it, and she said the idea was based on its anticonvulsant action, i.e., Robert Post's ideas. But here’s where the whole story comes together — where the two research paths finally intersect. The second type of bipolar — the female-predominant, irritable-mixed-switchy subtype — may have something to do with intracellular fluid retention.
I assume you know how to use Sci-hub? Check these out, keep an eye/ear out for this idea of "irritablity" and "inner tension".
Its the best book I've ever read on the history of mental illness. David outlines some of his hypothesis but only in a vague way, so if you don't know, you could miss it. He's a very scientific thinker so he presents it very tentatively and even when pressed he is extremely frugal in what he is willing to speculate. But if I had to "bet the ranch" on who is going to solve Aksiskal's "BPD mystery", I think David is damn close to cracking it and I'd be keeping an eye on his blog.
Thanks for this. A lot of what you’ve mentioned I’ve definitely not read. I have an interest in the history of borderline, but have read basically nothing about the history of bipolar except incidentally. So I’ll check some of this out.
"Let the old men read the new books; you students should read the journals, and the old books." - William Osler
You could have fooled me. I should read more about borderline. There is something there in women's mental health, something just out of reach. The cortisol stuff is interesting, there is a hypothesis that exposure to chronically elevated cortisol during childhood is the problem. I've spoken to Jayshri Kulkarni about it, she's very persuasive but quite eccentric, a good scientist though and very curious.
Bernard Carroll never found a cortisol issue in those female cases with his DST, you know about the DST right? Although, the bad boy of psychiatry, Charles Nemeroff, good scientist, sticky pharma fingers, he had 1 mixed state case that had the highest DST result recorded, young man, history of chronic trauma if I recall, fact check that. Might have been a fluke. Still there is something there.
Alec Coppen said there are three horses, endocrine, electrolyte, and neurotransmitters. The last one gets all the attention and of course no findings in borderline, much to chagrin of the pharmaceutical companies. But the second one, electrolytes, now that, fluid, that rings a bell with women. The first one of course is even more of a no brainer but do you think they can find any abnormalities? Back in the 1940s 50s, there were a few rapid cycloid cases treated with salt restriction.
Read David's book, he never toots his own horn but the man is brilliant. The drug harm stuff is like 1% of what he gets up to and that on its own is brilliant. One of his main interests is the disappearance of biological mental illnesses. That is to say, he's particularly interested in mental illnesses that appear to be biological and yet have dramatically decreased. He thinks it might offer a window into the biological etiology. Pretty clever.
Another great resource is the old inhn.org website. It's got many of the interviews David and Edward did interviews with some of the more famous psychopharmacologists. There is loads of information that you won't find in a journal, things that people learn from experience that can't really be published scientifically so to speak.
You should also read Kraepelin's textbook. Skip dementia praecox and read the chapters on manic depression, but also read the one on Amentia, not dementia, Amentia, that was his term for women who developed bipolar symptoms under stressful life events. His chapter on neurasthenia is also worth reading. Then read Wernicke's textbook, you can find the DOI for the English translation and put that in sci hub and get the whole whole translation. Pay attention to the term ratlosigkeit, it's an interesting term, it has a parallel to the confused delusional state of schizophrenia but tantalisingly it also encompasses the dreamlike dissociation of some of the more severe borderline cases. ChatGPT described it as "the feeling of being lost at a familiar bus stop" and Grok said it means "puzzlement but with an expansive sense of existential dread".
Then read Koukopoulos and Akiskal. They're both very eccentric so don't believe everything they say, it's very impressionistic but important, although much of it probably a little wrong. Then read Bernard Carroll's work, and Tom Ban. That should bring you up to speed. Fasted way is to just read Edward Shorter's books. Lastly listen to Osler's advice, read the old books, Schou and Coppen had some interesting stuff on the way lithium competes with sodium, those electrolytes again. Most of the new research is not so good, if you read Hannah Decker's book on the DSM you'll understand why. They were closer to figuring out borderline in the 80s if you ask me, so use PubMeds date range filter.
Oh and read Charles Nemeroff's work, he's a very naughty boy but a good scientist non-the-less and he's done a lot with cortisol since Bernard Carroll died, even though Bernard road him for years over the pharmaceutical payouts. Oh oh and Ian Brockington has some lectures up on YouTube talking about cycloid and bipolar in women. Oh and watch Nassir's lectures, he's too influenced by Akiskal and Kouk but he's got some good ideas.
You seem to be aware of the historical background of borderline, and your description of the psychopharmacological approaches is freakishly accurate.
I assume you've read Hannah Decker's book and know how borderline ended up in the DSM?
I assume you've read all of Edward Shorter's books?
I assume you're familiar with Hagop Akiskal's agony over borderline — his idea of “lamotrigine deficiency syndrome,” and how the diagnosis vexed him throughout his career?
I’m guessing you already know all of that.
But have you read Ian Brockington and Carlos Perris’s work on cycloid psychosis?
What about David Healy’s research on the women admitted to the Denbigh asylum in North Wales?
If you're anything like me, you probably followed the Kraepelin–Jules Angst–Robert Post–Akiskal–Koukopoulos–Baldessarini lineage — the Boston–Rome pathway. But there's another route, often overlooked: Angst’s research partner Carlos Perris followed a different trajectory, diving into WKL nosology. That path leads through Wernicke, Kleist, Leonhard, Fish, Perris, Brockington, and Bernard Carroll. The secret to the second path is that Perris and Brockington focused on peripartum and perimenstrual cases, and Carroll took this and focused on the endocrine system. The idea they had was that by examining de novo episodes of bipolar in the postpartum period, it might reveal a distinct phenotype, with discrete etiology and pathogenesis — or rather, you would at least know the etiology involves postpartum effects, thus ruling out a big chunk of other possibilities.
Both lineages have borne fruit in terms of treatment, and together they hint at something deeper: bipolar might actually consist of two distinct diseases — but not Bipolar I and II as we currently define them.
By now you've probably read about how David Dunner rushed the bipolar I/II split, and how he later regretted it. The real split might be between periodic illness and cycloid illness.
And this is where Bernard Carroll may have come close to solving the other half of the puzzle that Koukopoulos and Akiskal were chasing. For years, Akiskal, Koukopoulos, and Baldessarini were noticing a subset of patients who “switch” very suddenly, with more “mixity.” Carroll, meanwhile, was researching premenstrual tension — and I don’t mean “PMS” or “PMDD.” I mean tension — inner agitation, explosive rage, irritability — a distinct syndrome that separates out from PMS and PMDD.
Here’s the strange part: Carroll’s phenotype bears an uncanny resemblance to akathisia and the more extreme, volatile presentations of borderline. Think of the old “larval epilepsy” cases — what Falret and even Kraepelin thought might be post-ictal states. The big kicker though is that it also resembles these mixed switching types that Akiskal, Kouk and Ross were so interested in, the "irritable" ones.
Picking up on that thread, a few years ago Gabriel Sani tried treating PMDD with acetazolamide — with incredible results. I asked Alexia about it, and she said the idea was based on its anticonvulsant action, i.e., Robert Post's ideas. But here’s where the whole story comes together — where the two research paths finally intersect. The second type of bipolar — the female-predominant, irritable-mixed-switchy subtype — may have something to do with intracellular fluid retention.
I assume you know how to use Sci-hub? Check these out, keep an eye/ear out for this idea of "irritablity" and "inner tension".
https://rxisk.org/antidotes-for-akathisia-and-dysregulation/
https://www.mcleanhospital.org/video/lecture-mixed-features-mood-disorders-historical-and-current-clinical-implications
https://www.youtube.com/watch?v=VHpWh0fsyVI
https://www.mcleanhospital.org/video/lecture-mixed-features-mood-disorders-historical-and-current-clinical-implications
https://www.youtube.com/watch?v=VHpWh0fsyVI
https://pubmed.ncbi.nlm.nih.gov/24605130/#
https://pubmed.ncbi.nlm.nih.gov/7193399/
Oh and read this book: https://www.amazon.com.au/Mania-Short-History-Bipolar-Disorder/dp/1421403978
Its the best book I've ever read on the history of mental illness. David outlines some of his hypothesis but only in a vague way, so if you don't know, you could miss it. He's a very scientific thinker so he presents it very tentatively and even when pressed he is extremely frugal in what he is willing to speculate. But if I had to "bet the ranch" on who is going to solve Aksiskal's "BPD mystery", I think David is damn close to cracking it and I'd be keeping an eye on his blog.
Thanks for this. A lot of what you’ve mentioned I’ve definitely not read. I have an interest in the history of borderline, but have read basically nothing about the history of bipolar except incidentally. So I’ll check some of this out.
"Let the old men read the new books; you students should read the journals, and the old books." - William Osler
You could have fooled me. I should read more about borderline. There is something there in women's mental health, something just out of reach. The cortisol stuff is interesting, there is a hypothesis that exposure to chronically elevated cortisol during childhood is the problem. I've spoken to Jayshri Kulkarni about it, she's very persuasive but quite eccentric, a good scientist though and very curious.
Bernard Carroll never found a cortisol issue in those female cases with his DST, you know about the DST right? Although, the bad boy of psychiatry, Charles Nemeroff, good scientist, sticky pharma fingers, he had 1 mixed state case that had the highest DST result recorded, young man, history of chronic trauma if I recall, fact check that. Might have been a fluke. Still there is something there.
Alec Coppen said there are three horses, endocrine, electrolyte, and neurotransmitters. The last one gets all the attention and of course no findings in borderline, much to chagrin of the pharmaceutical companies. But the second one, electrolytes, now that, fluid, that rings a bell with women. The first one of course is even more of a no brainer but do you think they can find any abnormalities? Back in the 1940s 50s, there were a few rapid cycloid cases treated with salt restriction.
Read David's book, he never toots his own horn but the man is brilliant. The drug harm stuff is like 1% of what he gets up to and that on its own is brilliant. One of his main interests is the disappearance of biological mental illnesses. That is to say, he's particularly interested in mental illnesses that appear to be biological and yet have dramatically decreased. He thinks it might offer a window into the biological etiology. Pretty clever.
Another great resource is the old inhn.org website. It's got many of the interviews David and Edward did interviews with some of the more famous psychopharmacologists. There is loads of information that you won't find in a journal, things that people learn from experience that can't really be published scientifically so to speak.
You should also read Kraepelin's textbook. Skip dementia praecox and read the chapters on manic depression, but also read the one on Amentia, not dementia, Amentia, that was his term for women who developed bipolar symptoms under stressful life events. His chapter on neurasthenia is also worth reading. Then read Wernicke's textbook, you can find the DOI for the English translation and put that in sci hub and get the whole whole translation. Pay attention to the term ratlosigkeit, it's an interesting term, it has a parallel to the confused delusional state of schizophrenia but tantalisingly it also encompasses the dreamlike dissociation of some of the more severe borderline cases. ChatGPT described it as "the feeling of being lost at a familiar bus stop" and Grok said it means "puzzlement but with an expansive sense of existential dread".
Then read Koukopoulos and Akiskal. They're both very eccentric so don't believe everything they say, it's very impressionistic but important, although much of it probably a little wrong. Then read Bernard Carroll's work, and Tom Ban. That should bring you up to speed. Fasted way is to just read Edward Shorter's books. Lastly listen to Osler's advice, read the old books, Schou and Coppen had some interesting stuff on the way lithium competes with sodium, those electrolytes again. Most of the new research is not so good, if you read Hannah Decker's book on the DSM you'll understand why. They were closer to figuring out borderline in the 80s if you ask me, so use PubMeds date range filter.