What Do PTSD, GABA & MAOI Antidepressants Have In Common?
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Those are:
- PTSD: Post-Traumatic Stress Disorder
- GABA: Gamma-Amino Butyric Acid (a neurotransmitter)
- MAOI: Mono-Amine Oxidase Inhibitor (a class of drug that, you guessed it, inhibits monoamine oxidase—and is mostly prescribed as antidepressants)
Aside from being four-letter initialisms, what do they have in common?
The answer is—to borrow from Lemony Snicket—a series of unfortunate events.
Action, reaction
The series of unfortunate events goes like this: trauma → PTSD → astrocyte dysregulation → increased MOAB → increased GABA → decreased forgetting of things we’d rather not keep remembering all the time.
PTSD is, of course, Not Fun™. And, that’s where it starts. A traumatic experience leads to post-traumatic stress; this is not resolved (and quite possibly cannot be resolved, per se) and it persists, having enough of an effect on life to be called a disorder.
In reality, of course, it seems to be a very normal response to such experiences, so calling it a disorder may be a misnomer, but that’s the convention.
Recently, a team of researchers (Dr. Sujung Yoon et al.) investigated how this happens, physiologically, and how that physiological process might be interrupted.
First, they used high-tech tools (single‑cell RNA sequencing and chromatin profiling) to examine postmortem brain tissue from people diagnosed with PTSD, focusing on cells in areas* involved in fear regulation and emotion, to see which genes were turned on or off, and in which specific cell types.
What they found, in few words:
Astrocytes (a kind of glial cell, a support cell in the brain) produce excess GABA in PTSD, which blocks the brain’s ability to extinguish fear memories. Further, the enzyme monoamine oxidase B (MAOB) is responsible for this build-up, meaning that MAOB inhibitors (a subcategory of MAOIs, which as a class can inhibit MAOA, MAOB, or both) could treat PTSD
This next part has only been done in mice so far (there’s a process, working its way to live human trials), but they found that MAOI drug with the snappy name of KDS2010 (which is specifically an inhibitor of monoamine oxidase B) reversed PTSD-like symptoms in mice by lowering GABA, and restoring blood flow to where it was needed, thus enabling the then-natural process of fear memory deletion.
Why this matters: these molecular findings give clinicians actionable targets—and can lead to a physiological treatment for what is currently treated as a purely psychological condition.
You can read the paper in full, here: Astrocytic gamma-aminobutyric acid dysregulation as a therapeutic target for posttraumatic stress disorder ← it goes into more detail than we have here (obviously), including identifying some of trauma’s long-lasting epigenetic marks—changing how genes are regulated in different neuronal and non-neuronal (e.g. glial, like the astrocytes we talked about) cells. We’ll quickly mention, for example, that they identified specific genes (like ELFN1, MAD1L1, KCNIP4, SST, FKBP5) and regulatory variants whose activity shifts in PTSD, so those can become targets for treatment, too.
Want a drug-free way while you wait?
There are some options.
Firstly, let’s mention that if your PTSD is C-PTSD, which is PTSD, But, Well…. Complex, then while that’s less well-understood in popular culture, it is actually easier to treat. We explain how, here: Undoing The Damage Of Life’s Hard Knocks ← which, really, is also a huge key to psychological resilience for everyday life.
If it’s the more classic “there is a singular bad thing that you can easily be caused to remember by unwanted triggers associated with it, and you suffer as a result”, then many people find that this helps: Eye Movement Desensitization & Reprocessing (EMDR) ← keeps the memories, reduces the psychological impact (for those for whom it works).
Then, if that doesn’t work, there is also this: The Dark Side Of Memory (And How To Stop Revisiting Those Memories) ← basically, doesn’t truly delete the memory, but rather removes the memory from easy access, making it nigh-impossible to remember unless given hyperspecific recall cues.
Now, we mentioned in that article that it may not be appropriate for important memories (i.e. that you might need, and/or that form a core part of who you are that you don’t want to change). So, as ever, we recommend getting guidance from your local trustworthy mental health professional, of course. But it’s worth mentioning here, for your information.
Writer’s note: when I wrote that last article about memory removal, I (for obvious reasons) forgot something, which I was given cause to remember this morning. Specifically: that while the above-mentioned memory-removal technique will make the memories very difficult to access by your conscious mind, your subconscious will have still free access to them. In this case, it means that, for example, you will still be able to have nightmares about The Bad Thing™, and if you do, you’ll then remember it when you wake up and thus functionally have full access to those memories again, as the nightmare basically dug it up and left it on your pillow for you to contemplate upon awakening.
Take care!
PS: hiding this in a postscript because it’s very much not a drug-free way… But interestingly (this writer has not tried this one personally, nor does she plan to, but it’s an option worth mentioning), THC gets prescribed for some sleep disorders, in cases where the initial sleep disruption was because of nightmares, as it will reduce those (along with any other dreams, as collateral damage): Clinical Management of Sleep and Sleep Disorders With Cannabis and Cannabinoids: Implications to Practicing Psychiatrists
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Avocado vs Smoked Salmon – Which is Healthier?
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Our Verdict
When comparing avocado to smoked salmon, we picked the avocado.
Why?
In terms of macros, these are quite dissimilar, despite often fulfilling a similar culinary role; avocado has a lot of fiber (salmon has none) while salmon has a lot of protein (avocado has quite little). So far, so tied. When we look at fats, it gets interesting, because people often assume that all fish are fatty, and it’s not so; salmon are a rather lean fish, while avocado, meanwhile, is famously oily for a plant. This means that proportionally, salmon has more saturated fat, though avocado has more in total; avocado also has much more monounsaturated fat (proportionally and in total), while both foods have approximately equal omega-3. All in all, notwithstanding their many differences, the pros and cons are balanced, we we declare this category a tie.
In the category of vitamins, avocado has more of vitamins B1, B2, B5, B9, C, E, and K, while salmon has more of vitamins A, B3, B12, D, and choline. Superficially that’s a 7:5 win for avocado already, but it’s worth mentioning that avocados have a huge margin of difference when it comes to vitamins B9 and K (with more than 40x the vitamin B9, and more than 210x the vitamin K), which puts the result even further in avocado’s favor. So, a very clear win for avocado here.
When it comes to minerals, avocado has more magnesium, manganese, potassium, and zinc, while salmon has more copper, iron, phosphorus, and selenium. That’d be a 4:4 tie, but salmon also has around 100x the sodium, which makes this category a win for avocado.
In terms of phytochemicals, avocado has some beneficial flavonols, while salmon has nothing because, well, it’s not plant. That said, the numbers are very low for avocado, sufficient that for practical purposes, we could call this round a tie, even if the win should technically go to avocado.
There are a couple of extra things that salmon normally has that avocado doesn’t: salmon usually contains antibiotics and heavy metals. If it’s farmed, it’ll be super high in antibiotics (that’s very bad) unless the company has clear outside testing certifications attesting to the contrary; if it’s wild-caught, then antibiotics levels can be expected to be relatively lower, though antibiotic pollution levels are rising in rivers and the coastal waters they discharge into. Please also do not fall for greenwashing; a “clean” aesthetic does not mean the product is free from contaminants (and almost no fish will be completely free from heavy metals these days). Needless to say, both of these things count against salmon, and thus mean an extra point or two for avocado in comparison.
Adding up the sections makes a clear overall win for avocado, but as we say, both have their merits, so do enjoy either or both!
Want to learn more?
You might like:
Farmed Fish vs Wild Caught: Important Differences
Enjoy!
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Saunas: Health Benefits (& Caveats)
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The Heat Is On
In Tuesday’s newsletter, we asked you your (health-related) opinion on saunas, and got the above-depicted, below-described, set of responses:
- About 53% said it is “a healthful activity with many benefits”
- About 25% said it is “best avoided; I feel like I’m dying in there”
- About 12% said “it feels good and therefore can’t be all bad”
So what does the science say?
The heat of saunas carries a health risk: True or False?
False, generally speaking, for any practical purposes. Of course, anything in life comes with a health risk, but statistically speaking, your shower at home is a lot more dangerous than a sauna (risk of slipping with no help at hand).
It took a bit of effort to find a paper on the health risks of saunas, because all the papers on PubMed etc coming up for those keywords were initially papers with “reduces the risk of…”, i.e. ways in which the sauna is healthy.
However, we did find one:
❝Contraindications to sauna bathing include unstable angina pectoris, recent myocardial infarction, and severe aortic stenosis.
Sauna bathing is safe, however, for most people with coronary heart disease with stable angina pectoris or old myocardial infarction.
Very few acute myocardial infarctions and sudden deaths occur in saunas, but alcohol consumption during sauna bathing increases the risk of hypotension, arrhythmia, and sudden death, and should be avoided. ❞
~ Dr. Matti Hannuksela & Dr. Samer Ellahham
Source: Benefits and risks of sauna bathing
So, very safe for most people, safe even for most people with heart disease, but there are exceptions so check with your own doctor of course.
And drinking alcohol anywhere is bad for the health, but in a sauna it’s a truly terrible idea. As an aside, please don’t drink alcohol in the shower, either (risk of slipping with no help at hand, and this time, broken glass too).
On the topic of it being safe for most people’s hearts, see also:
Beneficial effects of sauna bathing for heart failure patients
As an additional note, those who have a particular sensitivity to the heat, may (again please check with your own doctor, as your case may vary) actually benefit from moderate sauna use, to reduce the cardiovascular strain that your body experiences during heatwaves (remember, you can get out of a sauna more easily than you can get out of a heatwave, so for many people it’s a lot easier to do moderation and improve thermoregulatory responses):
Sauna usage can bring many health benefits: True or False?
True! Again, at least for most people. As well as the above-discussed items, here’s one for mortality rates in healthy Finnish men:
Not only that, also…
❝The Finnish saunas have the most consistent and robust evidence regarding health benefits and they have been shown to decrease the risk of health outcomes such as hypertension, cardiovascular disease, thromboembolism, dementia, and respiratory conditions; may improve the severity of musculoskeletal disorders, COVID-19, headache and flu, while also improving mental well-being, sleep, and longevity.
Finnish saunas may also augment the beneficial effects of other protective lifestyle factors such as physical activity.
The beneficial effects of passive heat therapies may be linked to their anti-inflammatory, cytoprotective and anti-oxidant properties and synergistic effects on neuroendocrine, circulatory, cardiovascular and immune function.
Passive heat therapies, notably Finnish saunas, are emerging as potentially powerful and holistic strategies to promoting health and extending the healthspan in all populations. ❞
~ Dr. Jari Laukkanen & Dr. Setor Kunutsor
(the repeated clarification of “Finnish sauna” is not a matter of fervent nationalism, by the way, but rather a matter of disambiguating it from Swedish sauna, which has some differences, most notably a lack of steam)
That reminds us: in Scandinavia, it is usual to use a sauna naked, and in Finland in particular, it is a common social activity amongst friends, coworkers, etc. In the US, many people are not so comfortable with nudity, and indeed, many places that provide saunas, may require the wearing of swimwear. But…
Just one problem: if you’re wearing swimwear because you’ve just been swimming in a pool, you now have chlorinated water soaked into your swimwear, which in the sauna, will become steam + chlorine gas. That’s not so good for your health (and is one reason, beyond tradition and simple normalization, for why swimwear is usually not permitted in Finnish saunas).
Want to read more?
You might like our previous main feature,
Turning Up The Heat Against Diabetes & Alzheimer’s ← you guessed it, sauna may be beneficial against these too
Take care!
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Super Agers – by Dr. Eric Topol
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You may be wondering what sets this book apart from all the other “let’s look at what supercentenarians do” books.
And the answer is: this one is, as the subtitle suggests, more strongly evidence-based. We say “more strongly”, because the others are evidence-based too, but that evidence base in those cases is mostly observational studies (due to the difficulty of doing randomized controlled trials (RCTs) with this kind of thing, because of the population samples required). This one addresses that by taking the conclusions from the observational studies (and interventional studies and RCTs, where possible) and then doing science to all of the constituent parts, for which there is RCT-derived evidence.
Thus, Dr. Topol takes us through the evidence for various factors, including dealing with obesity and diabetes, reducing cardiovascular disease, avoiding cancer, and deferring (ideally indefinitely) neurodegeneration, as well as controlling our immune system (both ways; defending against external threats while not falling to internal autoimmune problems), and even a chapter devoted to the critical role of promoting mental health, without which the rest of health won’t do us any good. Again, all based on the evidence of how each intervention helps us to live longer, measurably healthier lives.
The style is on the hard end of pop-science, sometimes slipping into outright academia before (it seems) the editor got let back into the room. It’s still lighter reading than actual academic papers, and for those who do like reading actual academic papers, there are 98 pages of bibliography at the back. So, taking up the entire last quarter of the book, basically.
Bottom line: if you’d like very evidence-based deep insights into what actually enables us to live the longest, healthiest lives, then this is a top-tier book for you.
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Cleaning Up Your Mental Mess – by Dr. Caroline Leaf
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First of all, what mental mess is this? Well, that depends on you, but common items include:
- Anxiety
- Depression
- Stress
- Trauma
Dr. Caroline Leaf also includes the more nebulous item “toxic thoughts”, but this is mostly a catch-all term.
Given that it says “5 simple scientifically proven steps”, it would be fair if you are wondering:
“Is this going to be just basic CBT stuff?”
And… First, let’s not knock basic CBT stuff. It’s not a panacea, but it’s a great tool for a lot of things. However… Also, no, this book is not about just basic CBT stuff.
In fact, this book’s methods are presented in such a novel way that this reviewer was taken aback by how unlike it was to anything she’d read before.
And, it’s not that the components themselves are new—it’s just that they’re put together differently, in a much more organized comprehensive and systematic way, so that a lot less stuff falls through the cracks (a common problem with standalone psychological tools and techniques).
Bottom line: if you buy one mental health self-help book this year, we recommend that it be this one
Click here to check out Cleaning Up Your Mental Mess, and take a load off your mind!
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10 Ways To Naturally Boost Dopamine
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Dopamine is the “reward” hormone, and is responsible for motivation, as well as various oft-forgotten functions (such as spatial skills, motor functions, task processing, planning, and language). Sometimes, our relationship with dopamine isn’t what it could be, so here’s how to fix that:
Let’s get hormone-hacking…
Here are the 10 ways:
- The seesaw effect: reduce overstimulation by taking tolerance breaks from high-dopamine activities that aren’t particularly useful (like social media or phone games), allowing for natural enjoyment of daily activities that you’d normally find enjoyable. Think: if you died and negotiated to be sent back to life on the condition you’d appreciate it properly this time, what things would you then spend your time doing? It’s probably not Kingdom Crush Saga Farm 2, is it?
- Conscious state meditation: practise conscious state meditation, focusing inward to reduce anxiety and release dopamine. Even a few minutes a day can significantly enhance dopamine levels.
- Hack your REM cycles: optimize sleep, especially REM cycles, which produce the most dopamine. Aim to wake up after your final REM cycle to feel energized and happy.
- The runner’s high: engage in regular exercise, which boosts dopamine through physical exertion and can lead to feelings of relaxation and euphoria, often known as the “runner’s high.”
- Mood-enhancing music: listen to music that makes you feel good. Favorite songs can stimulate dopamine production, improving your mood and well-being.
- Bright light therapy: spend time in natural sunlight to stimulate dopamine production and elevate your mood, countering the negative effects of extended indoor time. If natural sunlight is not very available where you are (e.g. this writer who lives next to an ancient bog surrounded by fog and the days are getting short, at time of writing), then artificial daylight lamps are respectable supplement—but just that, a supplement, not a replacement. Despite how it looks/feels, natural sunlight (especially in the morning, to cue the circadian rhythm to do its thing) is beneficial even through cloud cover.
- Relieve stress for good: actively reduce stress, as it inhibits dopamine. Simplify daily routines and eliminate stressors to naturally boost dopamine and feel more relaxed. Of course, you cannot remove all stress from your life, so get good at managing the stress created by the stressors that do remain.
- Tap into your flow state: enter a “flow state” by focusing deeply on an engaging task, which can elevate dopamine levels and boost motivation and happiness.
- The hormesis effect: embrace mild physical challenges, like cold showers. The temporary discomfort will paradoxically increase dopamine (it’s the body’s way of saying “congratulations, you survived the hard thing, here’s a little treat, so that you’ll be motivated to survive the next hard thing, too”)
- Activate your inner artist: engage in creative activities that you find fun. The process of creating boosts dopamine and provides motivation, enhancing mood and enjoyment in life.
For more on all of these, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
Rebalancing Dopamine (Without “Dopamine Fasting”)
Take care!
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HRT Side Effects & Troubleshooting
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This is Dr. Heather Hirsch. She’s a board-certified internist, and her clinical expertise focuses on women’s health, particularly in midlife and menopause, and its intersection with chronic diseases (ranging from things associated with sexual health, to things like osteoporosis and heart disease).
So, what does she want us to know?
HRT can be life-changingly positive, but it can be a shaky start
Hormone Replacement Therapy (HRT), and in this context she’s talking specifically about the most common kind, Menopausal Hormone Therapy (MHT), involves taking hormones that our body isn’t producing enough of.
If these are “bioidentical hormones” as used in most of the industrialized world and increasingly also in N. America, then this is by definition a supplement rather than a drug, for what it’s worth, whereas some non-bioidentical hormones (or hormone analogs, which by definition function similarly to hormones but aren’t the same thing) can function more like drugs.
We wrote a little about his previously:
Hormone Replacement Therapy: A Tale Of Two Approaches
For most people most of the time, bioidentical hormones are very much the best way to go, as they are not only more effective, but also have fewer side effects.
That said, even bioidentical hormones can have some undesired effects, so, how to deal with those?
Don’t worry; bleed happy
A reprise of (usually quite light) menstrual bleeding is the most common side effect of menopausal HRT.
This happens because estrogen affects* the uterus, leading to a build-up and shedding of the uterine lining.
*if you do not have a uterus, estrogen can effect uterine tissue. That’s not a typo—here we mean the verb “effect”, as in “cause to be”. It will not grow a new uterus, but it can cause some clumps of uterine tissue to appear; this means that it becomes possible to get endometriosis without having a uterus. This information should not be too shocking, as endometriosis is a matter of uterine tissue growing inconveniently, often in places where it shouldn’t, and sometimes quite far from the uterus (if present, or its usual location, if absent). However, the risk of this happening is far lower than if you actually have a uterus:
What you need to know about endometriosis
Back to “you have a uterus and it’s making you wish you didn’t”:
This bleeding should, however, be light. It’ll probably be oriented around a 28-day cycle even if you are taking your hormones at the same dose every day of the month, and the bleeding will probably taper off after about 6 months of this.
If the bleeding is heavier, all the time, or persists longer than 6 months, then speak to your gynecologist about it. Any of those three; it doesn’t have to be all three!
Bleeding outside of one’s normal cycle can be caused by anything from fibroids to cancer; statistically speaking it’s probably nothing too dire,but when your safety is in question, don’t bet on “probably”, and do get it checked out:
When A Period Is Very Late (i.e., Post-Menopause)
Dr. Hirsch recommends, as possible remedies to try (preferably under your gynecologist’s supervision):
- lowering your estrogen dose
- increasing your progesterone dose
- taking progesterone continuously instead of cyclically
And if you’re not taking progesterone, here’s why you might want to consider taking this important hormone that works with estrogen to do good things, and against estrogen to rein in some of estrogen’s less convenient things:
Progesterone Menopausal HRT: When, Why, And How To Benefit
(the above link contains, as well as textual information, an explanatory video from Dr. Hirsch herself)
Get the best of the breast
Calm your tits. Soothe your boobs. Destress your breasts. Hakuna your tatas. Undo the calamity beleaguering your mammaries.
Ok, more seriously…
Breast tenderness is another very common symptom when starting to take estrogen. It can worry a lot of people (à la “aagh, what is this and is it cancer!?”), but is usually nothing to worry about. But just to be sure, do also check out:
Keeping Abreast Of Your Cancer Risk: How To Triple Your Breast Cancer Survival Chances
Estrogen can cause feelings of breast fullness, soreness, nipple irritation, and sometimes lactation, but this later will be minimal—we’re talking a drop or two now and again, not anything that would feed a baby.
Basically, it happens when your body hasn’t been so accustomed to normal estrogen levels in a while, and suddenly wakes up with a jolt, saying to itself “Wait what are we doing puberty again now? I thought we did menopause? Are we pregnant? What’s going on? Ok, checking all systems!” and then may calm down not too long afterwards when it notes that everything is more or less as it should be already.
If this persists or is more than a minor inconvenience though, Dr. Hirsch recommends looking at the likely remedies of:
- Adjust estrogen (usually the cause)
- Adjust progesterone (less common)
- If it’s progesterone, changing the route of administration can ameliorate things
What if it’s not working? Is it just me?
Dr. Hirsch advises the most common reasons are simply:
- wrong formulation (e.g. animal-derived estrogen or hormone analog, instead of bioidentical)
- wrong dose (e.g. too low)
- wrong route of administration (e.g. oral vs transdermal; usually transdermal estradiol is most effective but many people do fine on oral; progesterone meanwhile is usually best as a pessary/suppository, but many people do fine on oral)
Writer’s example: in 2022 there was an estrogen shortage in my country, and while I had been on transdermal estradiol hemihydrate gel, I had to go onto oral estradiol valerate tablets for a few months, because that’s what was available. And the tablets simply did not work for me at all. I felt terrible and I have a good enough intuitive sense of my hormones to know when “something wrong is not right”, and a good enough knowledge of the pharmacology & physiology to know what’s probably happening (or not happening). And sure enough, when I got my blood test results, it was as though I’d been taking nothing. It was such a relief to get back on the gel once it became available again!
So, if something doesn’t seem to be working for you, speak up and get it fixed if at all possible.
See also: What You Should Have Been Told About Menopause Beforehand
Want to know more from Dr. Hirsch?
You might like this book of hers, which we haven’t reviewed yet, but present here for your interest:
Enjoy!
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