Keep Your Eyes on AKT: It Might Explain How We Learn and Forget Fear

You may hear people say, “Antidepressants and other psych meds just don’t do anything…”

Some people say, “…placebos work better…” Oh please. But why do they say that?  Maybe their own experience with prescribed medicines was disappointing. So — of course — they’re disillusioned about these medicines. We get it. And we know that any given medicine that works for some people won’t help some others at all, or might even make them worse. Sooo… what’s up with that? Well, the answer isn’t simple. We do know that antidepressants,when first prescribed, only help about 30% of depressed people. We know that psych drugs help some people but not others and that men and women can experience depression and anxiety and fear differently. It’s a tangle to unravel it all. That’s why we’re so excited about new developments. We want to keep your eyes on AKT because it might explain how we learn and forget fear.

Meet Jill and Greg to see how differences affect their well being and livelihood:

Jill and Greg own a coffee shop together and are partners in life as well. They have a great balance of power, in the tasks they divide between them and the strengths they each bring. Greg is a people person, creative, funny, and efficient at both designing new drinks and training staff to make them just right. Jill is a numbers person, and sometimes comes off a little stiff and awkward, because she just doesn’t have Greg’s gift for setting people at ease. She also has some social anxiety going on.

She does ordering from suppliers, closes out the books every night, and keeps a close eye on profit and loss. They’re a perfectly matched pair and love working together. That is, as long as they’re both at their best. With Greg building relationships with customers and vendors, and Jill keeping the financial end sound, they really do provide strength for the weakness of the other.

Unfortunately, they both suffer from disorders that periodically causes some lost time at the shop. When that happens, the one who is doing OK ends up carrying a double load. And both of them struggle with anxiety… or basically fear on some level.

Greg was diagnosed with bipolar II disorder when he was a teenager. Jill was diagnosed with depression in college. She’s a worrier. He just explodes sometimes—and refuses to call it anxiety. Greg takes medication for mood stability that also has an antidepressant effect. Jill takes an antidepressant that only sort of works. They probably both need medicines that reduce anxiety.

In a perfect world…

Since their coffee shop venture requires all hands on deck to run smoothly, Jill and Greg are eager to find the right meds for both of them to help stay in the game. They need to be able to go in to work—they can’t afford not to. It seems to Greg that since his medication helps him as much as it does, Jill should ask her doctor to prescribe the same for her. She’s a nervous wreck! However, she knows enough about changing meds that she can’t just jump on another medication just because it works for Greg. She’s tried that before. It didn’t work.

At this point, Jill has tried five different antidepressants over the past few years, and has researched enough about IV ketamine treatment that she wants to talk to her doctor about whether she’s a candidate for it.

Considering something new takes a little bit of courage. She wasn’t sure what her psychiatrist would say. A visit with her psychiatrist surprised her–he was cautious but supported her trying something that might help. Jill decided to pay for it out of savings, because her bouts of severe depression were taking a toll on the shop and their income.

She arranged for treatment and began infusions. When the treatment was complete, she had received 8 infusions over about 3 weeks, and she felt like she had a new lease on life. Her ketamine infusions seemed to wake up her brain. And that got better and better day by day — even after she completed treatment. She found she enjoyed singing and dancing, and painting became her new passion. When they had a problem in the shop, she had so many more ideas for solving it. Working on the book work was no longer a drudgery–she enjoyed it and got more accomplished in a shorter time.

Jill and Greg’s life became so much better at work and at play. Greg still had slumps when his meds weren’t quite holding him, but their life was so much better overall. They had read that ketamine treatment could help bipolar depression, too. Maybe the next time he went through a bad bout of that, Greg would talk to his doctor about it. To see if it was right for him—not just to copy Jill.

Finding the right medicine for you is sometimes a long search. And medicine that works for you may not work for your sister…or your son. But it’s well worth the work researchers do to better understand why.

A research study at the University of Colorado Boulder offers one fascinating revelation about why those differences between people and genders might exist.

It has to do with a key protein kinase in the brain called AKT…which functions differently between males and females.

They found presence of a certain form of AKT (called an isoform) in male mice can help the male let go of fear from a past painful experience–and form a new adaptive response to get around the old fear. Wait, what? Doesn’t that remind you of the way synaptic plasticity helps you adapt?

Ok, you’re right…mice aren’t people and it doesn’t work quite that way…. but AKT is remarkably similar across mice and humans and this kind of translational research can begin to give us specific information to make our medicines and medical care more specific. Potentially even gender specific.

So you’ll do well to keep your eye on AKT because so much is being learned about how we learn and how we forget fear.

By figuring out the very complicated cascades involved in creating synaptic plasticity, we may be on the verge of figuring out how to shape and foster the neuroplasticity–for the better.

We may be able to personalize medication therapies so that they don’t just broadly address a disease state, but so that they can be specific for the man or woman who needs them. 

Charles Hoeffer, the principal investigator of this study, said it like this: “We need to stop hitting every ‘disorder’ with the same hammer.”  Well said! (Wish I had said that!)

We’re always talking about personalizing treatment. About how important it is to provide treatment that fits the individual. Just as that’s true with all of the fine details involved in ketamine treatment, it’s also true with all of the medicines we prescribe.

So… about AKT. 

It turns out AKT plays a lead role in synaptic plasticity. We’ve talked about that too…  The idea that the connections between cells in the brain can change and adapt. They can change and adapt as a result of an experience. (This is why trauma can change us.) But — so importantly — these connections can also grow, change, and adapt as a result of the deeply emotional experiences, like the incredibly deep and awe-filled experiences you can have during a ketamine infusion. So many of our patients do. We’ve talked about how taking advantage of that process by scheduling psychotherapy 24 hours after a ketamine infusion can enhance the effectiveness of the infusion. 

Why? Because therapy helps you think differently about something…and synaptic plasticity empowers those changes in thought. Many of our patients also find that journalling, creative writing, meditation and other activities help to integrate those experiences into their lives, find meaning in the experience, and move forward. Keep your eyes on AKT… there’s so much more to learn.

AKT helps you create memories. Like a child touching his hand to a hot stove. To encode that memory so that he will be cautious in the future around hot burners, his brain needs to activate protein kinases like AKT.

In fact, AKT is one of the first proteins to present itself to form a memory like that.

There are 3 main variants, or isoforms, of AKT and they do different things and affect people in different ways (More on that in a sec!)

AKT1 is important in encoding new experiences and allowing you to forget the old.

AKT2 is often found in the astroglia…which are star-shaped brain cells.

AKT3 seems to be important in brain growth and development. This one plays a positive role in mental health and wellbeing. 

And when AKT1 and AKT2 are working together in the prefrontal cortex, they’re vital for learning, for memory … for dynamic change.

Maybe like the kind of dynamic change that you want for yourself. So yes. So many different forms, working singly and sometimes together, in ways we are only now just beginning to understand for people suffering with psychiatric disorders.

Now. To add another twist to this picture. In this study, researchers found a dramatic difference between genders regarding AKT. 

They found that male laboratory animals whose AKT1 was functioning well, had far more ability to replace unwanted memories with new ones…than those who were missing AKT1. 

Draw that out for a moment now…. and imagine men who’ve experienced the trauma of illness, or assault, or combat… and imagine for a moment that they’re given the opportunity to experience something new — maybe hopeful, blissful, awe-filled, like they might during a ketamine infusion — and then the excitement of realizing that a tiny little protein kinase like AKT1 may play a part in helping to encode that new feeling. Turn it into a new memory. Make the old traumas fade. (That’s called extinction learning.) Teeny little AKT1 helps with this. In males. 

Incredible.

There are endless little nuances in your brain that translate your experiences, encode them, and shape your synapses…and your individual functioning. And maybe your future possibilities.

AKT is one to keep your eyes on for sure.

We keep learning, keep researching, and keep doing all we can to help you get better.

(Let’s just say we read all this stuff for fun–at nights, on the weekends, and at 5 am with a double shot of espresso.)

And at this point, serial titrated IV ketamine infusions still do the best job we’ve seen in bringing relief to more people with treatment-resistant depression and anxiety than just about anything else available today.

But ketamine treatment doesn’t work for absolutely everyone. Is it because of AKT or something different? We don’t know. Not yet. Researchers like the ones at Boulder are still searching to understand the nuances of dendritic growth and synaptic plasticity in order to refine our treatments–and discover better ones.

At Innovative Psychiatry, we personalize treatment to fit you — all the complexity and all the wonderfulness of you! And we aim for remission. Not just response. That’s the reason we titrate your dose, duration of the infusion, and the number of infusions you need to help you discover — once again — your best self.

When you struggle and suffer from the symptoms of disorders that can be tormenting and exhausting, getting treatment is paramount. And feeling safe is critical — so we have state-of-the-art technology that crushes 99.999% of all viruses and pathogens. During this pandemic we want to make things easy. We all need a little bit of easy.

So now, reach out for IV ketamine treatment in a safe atmosphere where this treatment can help you live better, hope more, and enjoy the challenges and relationships in your life that give your life meaning.

You can live a life of joy, fulfillment, accomplishment, and ongoing hope.

If your meds have not been providing you relief from symptoms of depression, despair, PTSD, or suicidal thoughts…call us.

Let’s talk about what you’ve tried that didn’t work. And if you’re a candidate for IV ketamine treatment, we can begin that.

Even though ketamine treatment isn’t for everyone, it just might be a good fit for you.

We’re here to help.

To the restoration of your best self,