Fearless Youth: Prozac Extinguishes Anxiety by Rejuvenating the Brain | Hacker News Reader

Fearless Youth: Prozac Extinguishes Anxiety by Rejuvenating the Brain

scientificamerican.com

68 pointstokenadult26 comments

Interesting behavioral study. However, the Scientific American authors make the conclusions appear a lot more concrete than they actually are.

Previously, researches have found that fluoxetine (Prozac) actually suppresses neuronal growth in vitro:

http://www.ncbi.nlm.nih.gov/pubmed/20377614

Fluoxetine treatment is often associated with an increase in BDNF (Brain-derived neurotrophic factor), a protein which encourages the development of new synapses in the brain areas responsible for higher-order thinking and other functions. At first glance this sounds great, as the Scientific American authors concluded. However, other researches, such as those in the study I linked above, hypothesize that this increase in BDNF and neuronal growth may actually be due to neuronal insult from fluoxetine. In other words, the increase in plasticity and new cell growth might be a healing response from the brain following damage caused by fluoxetine.

Furthermore, fluoxetine is an older SSRI with effects and receptor affinities that extend beyond the serotonin system. When using fluoxetine for research, caution must be taken to separate the effects on the serotonin system from the effects of other functions of fluoxetine. Without further study, we can't know if these effects apply to all SSRIs, or just fluoxetine.

I should also note: All of this is great for future R&D of next-generation anti-depressants, but it should not be used by anyone when determining a treatment path. Despite the study I linked above, to my knowledge we haven't seen any deleterious effects on memory or cognition due to SSRI treatment in the general population. The bottom line is that we don't know why or how SSRIs work (despite what the drug company marketing department wants you to believe), but they are effective for many people. And combined with therapy, the rate of remission improves even more.

"Previously, researches have found that fluoxetine (Prozac) actually suppresses neuronal growth in vitro"

Neurogenesis is only one type of plasticity, and it doesn't sound like the type they're talking about in this article. (Albeit I didn't read the study.)

While they didn't measure neurogenesis directly in the study, they did measure BDNF (Brain-derived neurotrophic factor) which can induce neuron growth[1]. Essentially they took two groups of mice: regular mice, and mice whose BDNF levels are believed to not respond to Prozac (Flx). They found that in regular mice, Prozac plus retraining reduced anxiety. In those mice in which Prozac doesn't increase BDNF, the Prozac effect went away.[2]

I know it's hard to read the actual study all the time, but sometimes it helps. :)

[1] http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_fact...

[2]Because mice heterozygous for the BDNF null allele (BDNF+/−) are insensitive to Flx treatment in behavioral models of depression and anxiety (3, 26), we tested whether BDNF+/− mice (C57Bl/6J background) responded differentially to Flx in the fear-conditioning paradigm. Flx again prevented fear renewal in the wild-type mice, but in BDNF+/− littermates trained to fully extinguish the fear response, the Flx effect was absent as indicated by elevated levels of freezing 1 week after extinction (Fig. 4B and fig. S7). To test whether BDNF was acting predominately in the amygdala, we used doxycycline-regulatable lentiviral infection to overexpress BDNF locally in the BLA from the end of extinction onward (figs. S8 and S9). BDNF-overexpressing mice did not show fear renewal, whereas control mice did (Fig. 4C).

Supporting online material for the related article in Science:

http://www.sciencemag.org/content/334/6063/1731/suppl/DC1

Abstract of the article, including link to a related resource:

http://www.sciencemag.org/content/334/6063/1731.short

The research finding here was surprising to me, so I submitted it even though it will eventually need more replication.

http://norvig.com/experiment-design.html

The research group involved in the research

http://www.helsinki.fi/neurosci/groups/castren_group.html

has an appropriate background for conducting this kind of research.

This preliminary finding about a serotonin reuptake inhibitor helping brain cells stay healthy is consistent with earlier findings I have read about in relation to lithium, another drug used to treat depression. Animal necropsy studies appear to show that lithium preserves nerve cells in the brains of animals treated with it as compared to controls. The references to this can be found in the standard medical textbook about mood disorders by Frederick Goodwin and Kay Redfield Jamison.

http://www.amazon.com/Manic-Depressive-Illness-Disorders-Rec...

So perhaps the findings generalize to the idea that preserving youthfulness ("plasticity," that is adaptability) of the brain helps people suffering from depressed mood develop new thought patterns, perhaps with additional help from talk therapy such as cognitive behavioral therapy.

Meh, this is just pro-pharma propaganda. Dozens of drugs increase brain plasticity, but you don't hear Eli Lilly funding journal articles saying that everyone should smoke weed or drop acid in combination with therapy. What exactly is so special about Prozac? Absolutely nothing.

It's not the Prozac that's the key in the study, despite the Scientific American angle:

What's significant here is that they were able to study the plasticity directly, and found that the reduced anxiety depended both on the Prozac (insert your favorite chemical here) and the re-training. And it compares it to a physiological difference in the two cases. That's novel, regardless of the drug. Prozac is a natural choice 1) because it's well studied, and 2) it has the well-documented clinical property of working best when combined with treatment (edit: therapy treatment).

How does this happen? Addressing this latter question is exactly what makes the study so cool: they identified physiological mechanisms that might cause this behavior, pending further research. Sure, they could ask the same questions with weed, or acid, or mushrooms, or caffeine. They happened to use Prozac.

Disclaimer: I do neuroscience, but not in this field.

Makes sense. The research is cool, I just take issue with the writeup that was submitted.

If prozac increases brain plasticity, I wonder if it could be used to enhance retraining of adults. For example, if you go back to college to learn a completely new field of work (say medicine or law), you could take prozac to make the process easier.

I swear I've seen a similar drug in a science fiction novel.

From what little I understand, you're absolutely right. Brain plasticity is simply your brain's potential to make lasting changes in its own physical structure.

The study cited by tokenadult says: "Fluoxetine treatment increased synaptic plasticity.. acted through local brain-derived neurotrophic factor." Brain-derived neurotrophic factor is a protein that facilitates plasticity, and there are a number of natural methods for boosting production of BDNF:

eat less; eat even less; fast once in a while; exercise regularly; eat turmeric; eat fish (or take a DHA supplement); do stuff with your brain.

I wish I had studies top of mind to cite, but most of this is summarized in a book called Power Up Your Brain: The Neuroscience of Englightenment (written by a neuroanatomist and a shaman). I read it after going on a 10-day Vipassana retreat and thinking that meditation is noninvasive neurosurgery. Effects differ depending on the style of meditation, but they all strengthen a fundamental pattern of brain activity, be it attentional control, physical awareness, emotional nonreactivity, compassion, etc, and there's plenty of studies documenting the neuroanatomical changes that result.

If you're interested in brain plasticity, look up Michael Merzenich, the UCSF research who coined the term neuroplasticity, on YouTube or TED.

eat less; eat even less; fast once in a while; exercise regularly

I've recognized the effects this has on my own brain, and you're absolutely right (for me, at least). And it makes me wonder about the origins of this particular chemical pattern, and how it came to be.

Perhaps it's some kind of evolutionary mechanism: back in the hunter/gatherer days, when food was scarce, those who had the particular genome to trigger the production of just the right set of chemicals for brain plasticity on an empty stomach were better able to form the neural pathways required for hunting and gathering food, thus able to survive.

This is a very good hypothesis. The underlying mechanisms may be older. The main culprits I have read are due to a reduction of insulin levels and an upregulation of stress/heat shock proteins.

The book has some discussion that supports this idea, including the suggestion that we survived a famine that Neanderthals / Cro-Magnon / others couldn't.

It does seem to make sense that increasing the ability to learn new behaviors would be beneficial if one was experiencing a food shortage.

I agree with the general sentiment that more natural approaches are healthier and generally more rewarding, but some people really benefit from medication. Yoga, meditation, diet and exercise are really good at improving a person's mental health in the 4-10 interval. But people who are down around 0-2 can't "meditate their way out of" depression or anxiety, and they often struggle even to get out of bed, much less exercise on a daily basis. For these people, medications can really help. To say that SSRIs are bullshit just because exercise and a decent diet can clear up mild depression is folly.

I agree, and didn't mean to imply otherwise.

I was going to ask the same thing about language learning; children are apt at learning languages and this seems like a way to reopen that window later in life.

Wow.. Prozac homestays.

With Prozac being one of the more mild antidepressants, one must imagine the results from even more refined drugs produced in recent decades. I also wonder how the mood stabilizers with antidepressant effects would intersect here.

But, remember that anxiety is one of the most common side effects of Prozac and similar drugs. Perhaps for every patient positively affected you have another who's anxiety is actually amplified.

Edit: Why downvote? This is both factual and informed by my anecdotal experience...

Be careful. Anxiety is a common side effect only at the beginning of SSRI treatment. Once serotonin receptors down-regulate to accommodate the new levels of extra-cellular serotonin, steady-state is reached and the anxiety usually abates.

Unfortunately, this causes many patients to abandon treatment before the the therapeutic value is apparent. This is one of the biggest obstacles in treating depression.

Of course, there are always exceptions. However, most of the time you will find that those who complain about SSRIs inducing anxiety did not actually wait long enough for the effects to become apparent.

Also, your suggestion that Prozac is one of the more mild SSRIs is completely backwards. Prozac is one of the earliest SSRIs and has a rather broad spectrum of receptor affinities. Newer SSRIs are more selective and have better side-effect profiles. Escitalopram is the gold standard here.

I guess we must agree to disagree that its only a side effect in the beginning. My clinicians experience and mine (personal and experiences I've heard in Group Therapy) differ, though I'm happily on another anti-depressant that works for me. For what its worth, Prozac's effects were negligible for me. I still recommend it as a first treatment for those with symptoms.

The same goes for my statement that Prozac is one of the more mild anti-depressants in terms in side effects. Its often the first prescribed, specifically for the reason that its effects (side and primary) are more mild, thus a safer place to baseline to start from.

He said that Prozac is one of the milder anti-depressants (not milder SSRIs). That's true. Prozac is coarse compared to the later SSRIs but not compared to the other categories of antidepressants (MAOI, tricyclic).

"Antidepressants may prime the adult brain to rewire faulty circuits during therapy."

Considered faulty circuits because stimuli was repeatedly presented with pain/an electric shock?

This article also doesn't tell us why it's seemingly plastic.

Also, it was only once the mice were removed the painful environment that ... so how about just remove people from a negative environment?

What happens to the mice if you put them on Prozac, and the pain is still there? Do they learn to fear it even greater/stronger?

Try this with MDMA along with therapy and you'll desensitize the mice/people too; http://www.maps.org/mdma/protocol/

Let me give you an example of 'painful environment,' something many people can probably relate to.

There's a kid. They're outgoing, talk to everyone, and adults constantly tell their parents what a smart kid they have.

Kid grows up a bit, and during puberty is constantly ridiculed in social environments. Eventually the kid withdraws into themselves - a shell of their former, outgoing self.

In their twenties, even though they aren't in the negative environment of getting ridiculed for every single last thing anymore, the mere act of talking to someone new induces feer and anxiety.

They know they need to be more social. That they aren't depresses them. They find alcohol a decent enough social lubricant, but it doesn't work as well as they hoped. So they use more of it. They may add a couple more drugs into the mix - a line of cocaine in the john will help liven them up, surely - and end in a flat-out spiral of drug and alcohol abuse coupled with crippling depression and social anxiety.

Their learned response to the stimulus of the social is emotional pain.

They go on prozac; they go into therapy; the increased brain plasticity helps the therapy hold; their response to social interaction is no longer flight-or-fight.

Get it, now?

This is a neat story. I'm a bit too eager to believe it. If I knew some neurology, I'd surely think of reasons to be sceptical.

What are they? Apart from the obvious one, that no one has repeated the experiment yet.

So the idea is to use Prozac to make it easier for therapy to reprogram a brain's responses to social situations that induce anxiety. I'd be curious to know what this says, if anything, about the kinds of problems that have less to do with fear/anxiety than something else, like autistic spectrum disorders. Would using antidepressants to help rewire a brain be effective then? It's a very cool idea regardless.

I've observed that flouxetine lowers ones inhibitions drastically, more like a stimulant than like alcohol. Interesting results, as they basically confirm this.

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