What Do PTSD, GABA & MAOI Antidepressants Have In Common?

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