Brexanolone for postpartum depression

Another take by Psychopharmacology Institute.

• Brexanolone is a synthetic form of allopregnagolone, a GABA modulating neurosteroid

• The study had 216 participants, all women 18-45 with de novo MDD in their third trimester or within the first 4 weeks following delivery

• The drug was administered via a 60-hour injection (despite a half-life of roughly 9 hours)

• The cumulative response rate of 81.4% in BRX versus 61.7% in PLA groups

• All the other outcomes p<0.05 better in BRX group

• The cost of such an injection is ~$34,000 before insurance and deductions (like WTF man)

• BRX can apparently cross BBB when administered intranasally, however, a lot is lost (16,000 ng/mg in the olfactory bulb ⇢ 670 ng/mg in the brain). The authors used cyclodextrin sulfobutylether-β-cyclodextrin to enhance the transport

• More on BRX

Finally, generative agents!

The long-awaited agent simulations of human behavior...tadaa...the ones that use Time-Weighted Vector Retriever. By the way, here it is.

And here's a demo which I've linked not once and not twice IIRC.

Alzheimer's and gut

• Some of the gut bacteria were found to be more prevalent in both AD patients and, in the present study, in the so-called preclinical stage

• One of those are Faecalibacterium prausnitzii

  

• A strange one as those are one of the main butyrate producers

• Turns out it actually has a possible link to immune system activation, being increased in RA patients and decreased in Sjogren's Syndrome and Systemic Sclerosis.

• The weird thing, yeah - F.S. is less abundant in AD than in healthy controls:

  

  • Still, the authors tell us that in preclinical AD, FP is more abundant (the things you do without institutional access). 👀🧐🔎

    

    

    

    Obviously, it's detected more often; but is it more abundant on the average, and does this make real sense concerning its effects?

  • 

I wouldn't run to conclusions and causal inference here. It may well be a correlation, or an adaptive change (say, as oxidative damage increases SOD/CAT/GPx expression, tau accumulation may slightly increase the butyrate producers, or some enzymes may produce more food for that phyla, etc.)

Tribalism

Just a wild thought:

May the cancel culture be rooted in the solitude everyone is experiencing (actually, not)? Maybe that's more in line with interconnectedness ⇢ exuberance and being fast to react?

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