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Peter's avatar

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.

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Peter's avatar

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.

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