# Perseverance is rimming a crater!

![](https://iili.io/2NG5HAb.png align="center")

[<s>Oh, I guess that's not what it says.</s>](https://t.me/science/3831?single) Nonetheless, Jezero crater is the current frontier for the mighty rover 🫶

![Probing the Red Planet: Finding past life at Jezero Crater | Space](https://cdn.mos.cms.futurecdn.net/5sA9kTxtUYXKicqQm87uk.jpg align="left")

<s>That’s a lot of rim to cover…</s>

# Mental health

## [Investigational treatments for MDD](https://psyandneuro.ru/novosti/treatments-for-major-depressive-disorder/)

![Major depressive disorder: hypothesis, mechanism, prevention and treatment  | Signal Transduction and Targeted Therapy](https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fs41392-024-01738-y/MediaObjects/41392_2024_1738_Fig1_HTML.png align="left")

Same new ([original article](https://www.bmj.com/content/386/bmj-2022-073823)):

* **psychedelics** (psilocybin, ayahuasca, DMT (obvious 5-MeO-DMT in, say, [Canada](https://www.fasken.com/en/knowledge/2022/01/health-canada-finally-restores-access-to-psychedelics))
    
* **mitochondrial** supplements (e.g. PQQ is not a silver bullet)
    
* **glutamate** modulation (ketamine/esketamine)
    
* [**neuropeptide** Y](https://www.perplexity.ai/search/overview-of-neuropeptide-y-and-wxMX_v.WSPCJcMSjvMYsPw): acts via four receptor types (Wiki also states Y6R is present, hehe) and modulates stress/HPA response, food and alcohol intake etc. But I wooouldn't say it's [that differing from placebo](https://academic.oup.com/ijnp/article/23/12/783/5917572?login=false)
    
* **neuromodulation** modalities:
    
    * rTMS
        
    * tDCS
        
    * LLLT
        
    * bright light therapy (as part of sleep deprivation - sleep phase shift - BLT)
        
    * deep brain stimulation etc.
        
* Another interesting target from [one of the articles](https://www.nature.com/articles/s41398-024-03031-6#Sec1) is [FKBP51](https://pubmed.ncbi.nlm.nih.gov/22581765/) - quoting:
    
    ![](https://www.frontiersin.org/files/Articles/1182345/fpsyt-14-1182345-HTML/image_m/fpsyt-14-1182345-g001.jpg align="left")
    

> In various psychiatric and neurodegenerative conditions, patients have shown specific **polymorphisms in the FKBP5 gene**, which plays a role in **negative feedback regulation**. Consequently, individuals with mutations in this gene experience **reduced sensitivity of glucocorticoid receptors, leading to uncontrolled CRH release**

I hope you were [doing some screenshots](https://t.me/ohmyboi/1346); babe I'm not a [crystal ball](https://t.me/just_discussions/13624) (*visit and play this game plz plz*) but...

## Again, [bipolar and mitochondria](https://psyandneuro.ru/stati/mitochondrial-dysfunction-and-bipolar-disorder/)

![](https://www.mdpi.com/brainsci/brainsci-14-01199/article_deploy/html/images/brainsci-14-01199-g002.png align="left")

* A nice infographics piece on factors involved ➡️ anything from f-ed up electron transport chain to apoptosis
    
* Think of it like that if you're a programmer - *a bug in a smart power supply software will make your computer act weird in every way imaginable* *because of voltage spikes and outages*
    

## [Benzos and their responsible prescription](https://psychopharmacologyinstitute.com/section/appropriate-benzodiazepine-use-indications-and-optimal-selection-2797-5680)

![](https://www.benzoinfo.com/wp-content/uploads/2021/05/Benzo-Conversion-Chart.png align="left")

Too simple:

* avoid **alprazolam** (short-acting and increasing extracellular dopamine ➡️ reinforcing and withdraw-y) and **clonazepam** for long-term use (potent and hard to taper)
    
* **lorazepam** is preferable, or **diazepam/clobazam** (yeah, the chart has Z-drugs in 'benzo' comparison, but it's a comprehensive one IMO)
    

## [Pharmacogenetics, a wee bit](https://psychopharmacologyinstitute.com/section/pharmacogenetic-tests-that-matter-in-psychiatric-practice-2827-5795)

![Pharmacogenomics in treatment of depression and psychosis: an update:  Trends in Pharmacological Sciences](https://www.cell.com/cms/10.1016/j.tips.2022.09.011/asset/90fc5dac-5b86-4550-9a14-9590b6b7e6d7/main.assets/gr1_lrg.jpg align="left")

[*Link*](https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147%2822%2900207-3)

* **P450** are here, obviously: 2D6, 3A4, 2C19
    
* I'd add [ABCB1/MDR1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3098758/#S5) as it influences the efficiency of scores of drugs, [including antidepressants](https://pmc.ncbi.nlm.nih.gov/articles/PMC7613909/#Sec7). Not a given, but some studies [suggest a strong link](https://pubmed.ncbi.nlm.nih.gov/17913323/) + [mitochondria](https://www.nature.com/articles/mi201731) + the whole ten yards of DNA strips
    

# Social

## [20% of US adults feel lonely everyday](https://greatergood.berkeley.edu/article/item/can_we_ease_loneliness_with_a_little_gratitude)

%[https://www.youtube.com/watch?v=lwLLFbC1H0c] 

* people **above average in gratitude** (say thanks, dammit!) were **62% less likely to feel lonely**
    
* the article has more studies on that, but why is that so?
    
    * authors suggest it's because of being **more flexible and adaptable**
        
    * maybe **being ready to ask for help matters**, too (just a wild guess)?
        
* OK to all the social anxiety folks here 🗿
    

## [Okay Metallica Green Day Tokio Hotel boomer.](https://www.statsignificant.com/p/when-do-we-stop-finding-new-music)

![](https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fd3e964cc-567c-47c2-9644-28938cfedc53_1224x814.png align="left")

* music you listen to in your teens (13-14 yo) influences your music tastes the most
    
* the funny thing is, highlighted by a great viz: 'best decade for music' depends on how old we are!
    
    ![](https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F665829d5-7189-460d-a5b1-08ab5af600a2_1248x880.png align="left")
    
* our music taste reaches maturity, yeah, in 30s:
    
    ![](https://substackcdn.com/image/fetch/w_1456,c_limit,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F10505c46-cb9d-47ca-a2f4-d2ae378a7fd4_1120x990.png align="left")
    
* the author highlights an awesome heuristic, **37% rule:** we spend the first 37% of available search time exploring our options before settling on a preferred solution or selection.
    
    * **<s>GOLDEN RATIO 100% - 37% = 63 ALMOST 61.8%</s>**
        
    * Okay that was too rash, possibly. <s>But THEY KNOW AND THEY ENGINEERED US THIS WAY</s>
        
    * mathematicians suggest dropping the first 37% of options for best outcome. It’s even [applied to dating](https://bigthink.com/neuropsych/the-37-percent-rule/)… Which seems a bit weird as how can one plan for X encounters then writing the 37th [*“Hey we met two years ago, but this is crazy! So here’s my number, let’s chat once more maybe”*](https://plus.maths.org/content/mathematical-dating)
        
    * [Heuristics like that](https://www.shortform.com/blog/37-rule/) may possibly reduce decision fatigue, my fellow big-frontal-lobe gents and gals 🫶
        
        ![What Is Decision Fatigue?](https://www.choosingtherapy.com/wp-content/uploads/2022/11/9-Tips-for-How-to-Avoid-Decision-Fatigue.png align="left")
        

## [Hate legal texts? They hate you for a purpose, too.](https://www.perplexity.ai/page/the-magic-spell-hypothesis-n5tkbs1JR4OGww9A25c9ZA)

![Вжух - что значит мем, смешные картинки, история и значение мема](https://v1rt.ru/upload/iblock/5dd/5ddc3d85587ef57025acef2872cdae50.jpg align="center")

* Scientists from MIT suggest legal texts being overly complex <s>and judicious while being expanded in needless and wordy text volume</s> is a form of **gatekeeping strategy**, to give the **sense of authority**
    
* The ‘overly complex’ effect persisted even in **recent legal texts**, not being combined of template parts - so it’s a learned trait (debunking so-called **Copy-and-Edit hypothesis**)
    
* For confirming the hypothesis, people were asked to **compare two spells: one overly complex and vague, other simple**. **Complex** ‘spells’ were rated as **more effective**
    
* However, some [are resisting the hypotheses](https://www.adamsdrafting.com/another-misleading-attempt-to-explain-why-legalese-is-the-way-it-is/)…
    

---

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