# Though(t)s [2023-08-14]

# [Brexanolone](https://psychopharmacologyinstitute.com/section/effect-of-brexanolone-on-postpartum-depressive-symptoms-anxiety-and-insomnia-2737-5503) for postpartum depression

![Frontiers | Allopregnanolone, the Neuromodulator Turned Therapeutic Agent:  Thank You, Next?](https://www.frontiersin.org/files/Articles/536318/fendo-11-00236-HTML-r1/image_m/fendo-11-00236-g001.jpg align="center")

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](https://en.wikipedia.org/wiki/Allopregnanolone))
    
* 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](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116426/), 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](https://nap.nationalacademies.org/read/26218/chapter/5)
    

# Finally, [generative agents](https://github.com/joonspk-research/generative_agents)!

The long-awaited agent simulations of human behavior...tadaa...the ones that use [Time-Weighted Vector Retriever](https://betterprogramming.pub/the-battle-of-the-agents-4-autonomous-ai-agents-d4e49341128d). By the way, [here it is](https://python.langchain.com/docs/modules/data_connection/retrievers/time_weighted_vectorstore).

And here's [a demo](https://reverie.herokuapp.com/arXiv_Demo/) which I've linked not once and not twice IIRC.

# [Alzheimer's and gut](https://www.sciencealert.com/differences-in-gut-bacteria-could-be-the-first-warning-signs-of-alzheimers)

* 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*
    
    ![Faecalibacterium Prausnitzii: An Anti-inflammatory Gut Microbe](https://atlasbiomed.com/blog/content/images/2021/03/f-prausnitzii-functions.png align="center")
    
* A strange one as those are one of the main [butyrate producers](https://www.nature.com/articles/ismej2016176)
    
* Turns out it actually has a possible [link to immune system activation](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300652/), being increased in RA patients and decreased in Sjogren's Syndrome and Systemic Sclerosis.
    
* The weird thing, yeah - [F.S. is less abundant](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509190/) in AD than in healthy controls:
    
    ![](https://cdn.hashnode.com/res/hashnode/image/upload/v1692044582793/1ab42cae-d818-4295-98d7-9dfb75cb24ab.png align="center")
    
    * Still, the authors tell us that in preclinical AD, FP is more abundant (the things you do without institutional access). 👀🧐🔎
        
        ![](https://cdn.hashnode.com/res/hashnode/image/upload/v1692045918504/02b0870a-e87f-44b4-86ab-369256028350.png align="center")
        
        ![](https://cdn.hashnode.com/res/hashnode/image/upload/v1692045944894/692710a3-20d7-4f06-872f-0adac1ebec3b.png align="center")
        
        ![](https://cdn.hashnode.com/res/hashnode/image/upload/v1692047306753/e9e1ccb2-439a-4fc4-8981-7135ba736f50.png align="center")
        
        Obviously, it's detected more often; but is it more abundant on the average, and does this make real sense concerning its effects?
        
    * ![](https://i0.wp.com/tattooonmybrain.com/wp-content/uploads/2023/06/Microbiome.png?resize=1024%2C629&ssl=1 align="left")
        

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](https://www.sciencedirect.com/science/article/pii/S2090506817301550), 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](https://en.wikipedia.org/wiki/Cancel_culture) be rooted in the solitude everyone is experiencing ([actually, not](https://ourworldindata.org/loneliness-epidemic))? Maybe that's more in line with interconnectedness ⇢ exuberance and being fast to react?

![How Long it Took for Popular Apps to Reach 100 Million Users](https://www.visualcapitalist.com/wp-content/uploads/2023/07/CP_Threads-Fastest-100-Million.jpg align="center")

---

Welcome to **Teleogenic/Boi Diaries**❣️

The places I try cross-posting to:

* [**Blog**](https://blog.teleogenic.com/)
    
* [**Medium**](https://baldr.medium.com/)
    
* [**Telegram**](https://t.me/ohmyboi)
    
* [**Twitter**](https://twitter.com/ZakharKogan)
    
* [**LinkedIn**](https://www.linkedin.com/in/zakhar-kogan/)