Category: depression


It looks like my goal of world domination have gotten a few steps closer, if two of the popular press articles I posted in the webliography are any indication.

The two articles form a theme of sorts about control.  One of the articles talks about how scientists hacked into a monkey’s brain to control its movements.  There have been reports in the literature describing procedures by which monkeys can control objects in the real world with their brains.  This is usually achieved by an implant of some sort that can be affected by certain patterns of electrical activity in the surrounding brain tissue that then sends a signal to a device in the real world.  This research seems promising for a variety of things, particularly people with paralysis or prosthetic limbs,   Imagine being able to control the prosthetic not only with the muscles near it, but also with your brain to some extent.

Schematic of brain showing the ventral tegmental area (VTA).

Schematic of the brain showing the ventral tegmental area.

Researchers have figured out an elegant way to influence the decision making process of monkeys.  They implanted electrodes into the ventral tegmental area (VTA) of the brain, which is one of the places (as you will learn more about in the coming weeks) that produces dopamine and is involved in reward circuitry of the brain.  Then, they conducted a simple preference test by showing monkeys two pictures of random objects and had them indicate which one they liked better.  This initial preference test was their control procedure since they were interested in what choices the monkeys made without any interference from the experimenters.  Once this was done, they demonstrated that by sending brief electrical bursts through the electrodes implanted in the monkeys brains the researchers could get the monkeys to reliably switch their preferences for pictures.  Now, this doesn’t mean an evil mustache-twirling mastermind, or the government, or the NSA are going to take over your mind or anything like that, though that possibility is certainly there.  But this does build on some fascinating research from the 1950s that helped to further our understanding of the role the brain plays in motivating our specific choices.  The fact that this can be manipulated artificially is an interesting finding.

Long-term potentiation

A schematic of a regular synapse and one that has undergone stimulation to produce a long-term potentiation (LTP).

In the other interesting article, researchers were able to turn memories off and on.  This was done in genetically engineered rats using light pulses that strengthened or weakened synapses in the hippocampus.  This is another thing you’ll be learning about (in Week 5 I think).  One of the amazing things about our nervous system is that it is dynamic and is constantly changing due to our experiences.  It’s why we can learn new things.  One of the ways memories are formed is through strengthening and weakening of synapses, or long-term potentiation (LTP) and long-term depression (LTD).  This strengthening and weakening can be achieved through everyday use, such as when you memorize information for this class, or become classically or operantly conditioned to perform a response to a specific stimulus.  It can also be artificially induced, using different frequencies of light pulses that stimulate the synapse.  If you can find the right frequency of pulses (high or low) you can make the synapse stronger or weaker.  This is the mechanism by which the researchers in this particular study were able to manipulate memory in the rats. They were able to turn a conditioned fear off and on using light pulses to the hippocampus.

Both of these studies are interesting for a couple of reasons.  First, they tie together a lot of the information you’ve already learned in the course, particularly how synapses and neurotransmitters work, as well as brain structure (VTA and hippocampus) and shows how they all work together to produce complex behavior.  The added layer that makes this particularly fascinating to me is the fact that researchers can control behavior through selective brain stimulation, an idea that is exciting and a little terrifying.  I will admit it does conjure up images of a MatrixThe Matrix-like culture where people’s thoughts and behaviors are controlled by others by directly accessing their brains.  It’s easy to see how something like that could be abused at some future point, though we’re a long way from that.

I can see some tremendous potential for good, here, too.  In particular, imagine what the treatment of extreme phobias, Alzheimer’s disease, PTSD, and other types of problems related to memories would look like if we had the ability to either enhance memories or take some memories away at will.  It’s tempting to shrink from an idea like that, because our memories are what make us who we are, and common sense tells us we might be better off learning to just cope with them.  But imagine memories so awful, so debilitating and disturbing, that it becomes difficult or impossible to cope with them, and they begin to affect every aspect of your life.  I’ve never suffered from PTSD, but I imagine it can be quite horrible, and if conventional treatment doesn’t help then perhaps being able to suppress the memories, at least for a little while so that other coping mechanisms can be acquired and strengthened might offer some people a desperately needed reprieve.  And being able to counter the synapse weakening amyloid beta proteins in the brains of people with Alzheimer’s Disease seems like a promising idea worth investigating.

It’s a little harder to see the benefits of influencing choice.  One can easily envision unscrupulous advertisers using something like this to force people to choose their products, but again, I doubt that would ever happen.  I think the significance of this centers on the issue of motivation.  They were able to manipulate motivation, and got monkeys to choose things they might not otherwise choose.  Though it’s a stretch, this might be something beneficial to people suffering from depression or inactivity of one sort or another.  The idea is interesting, anyway. I wouldn’t mind being able to give my brain a little zap to get me motivated.

References

Arsenault, J.T., Rima, S., Stemmann, H., Vanduffel, W. (2014). Role of the primate ventral tegmental area in reinforcement and motivation.  Current Biology, 24(12), 1347–1353 DOI: http://dx.doi.org/10.1016/j.cub.2014.04.044

Nabavi, S., Fox, R., Proulx, C.D., Lin, J.Y., Tsien, R.Y., and Malinow, R. (2014). Engineering a memory with LTD and LTP.  Nature, doi:10.1038/nature13294

Advertisements

DISCLAIMER:  I debated for a long time about whether or not to post this entry.  This entry is about my personal experiences with an herbal remedy. I am not advocating St. John’s Wort as an alternative to prescription anti-depressants or advocating self-medicating.  I was young when I did this, and, honestly, very stubborn and very stupid, and I got lucky; I would not treat my depression, or any other disorder from which I suffered, without professional help now.  If you are feeling depressed, I strongly recommend that you seek professional help, starting with your personal physician.

Everyone suffers from depression at some point in their life.  Like many of you, I have had my bouts with mild depression here and there, mostly in reaction to life events.  Normally, I just get through it, because it never gets so severe that I cannot see better days ahead.  I think I am a reasonably happy, well-adjusted person, and when I do feel depressed, it is usually in reaction to something going on in my life rather than a chronic state.

Blue MeaniesThere was one point in my life, however, where the depression, although mild, was protracted and began to become disruptive.  I was working on my dissertation, and also running a laboratory, working many hours a week.  I was experiencing depression over the state of my dissertation, because it felt like I could not make any significant headway on it.  Compounding those feelings were what a good friend of mine referred to as “the 3am blue meanies.”  Every night, I would wake up with an anxiety attack about my dissertation, at around 3am.  I would lie in bed and worry about how I was not going to finish my dissertation in time, that the experiments I had designed were not going to work anyway, and how I would flunk out of graduate school and be a total failure for the rest of my life.  Images of myself as a sad bag lady filled my head, and there would be no sleep for me for the rest of the night.

I did not have any health insurance at the time, so going to see a counselor was out of the question, since I could not afford it.  In desperation, I looked around on the internet (I know, right?) for some solution to my problem.  I focused on depression, since I was convinced my nightly anxiety was related to depression (I do not know why, I am not a clinician, but that is where my mind went).  I came across several references to an herbal remedy called St. John’s Wort (pronounced “wert” by the way), which was touted as a remedy for depression.

St. John's WortAt the time, there was little in the way of information, but most scientific sources said that it was probably no more effective than a placebo.  Several European journals, however, reported that it was effective in treating depression, and had relatively few side effects.  St. John’s Wort (Hypericum perforatum) is a yellow-flowering plant with many chemical properties that are not, to date, well understood.  It has been used for centuries to treat various disorders, including depression and anxiety.  It is a prescription medication in many places in Europe, but is available over-the-counter here from many health food stores.  Delivery methods include capsules and teabags.

I was admittedly dubious, but also desperate.  At the very least, I told myself, as I bought a bottle of the stuff, I hoped that my extensive reading on the subject would not negate a placebo effect, and there were few reported side-effects from taking it.  Dutifully, I began taking my two capsules of St. John’s Wort a day and waited for results.

At first, nothing happened.  I still kept waking up at night, I still felt depressed and anxious, and, on top of that, now I was disappointed, because this stuff obviously did not work.  However, I had read that it sometimes took a couple of weeks to work, and I knew enough about anti-depressant medication to know that that was also the case with those.  So I stuck it out, and continued taking the pills.

Lo and behold, the 3am blue meanies went away, more or less.  I still felt anxious and depressed about the state of my dissertation, but less so.  The lessening of the anxiety and the better sleeping at night led to more productivity, and I actually began to make progress on my studies again.  My general mood improved over the first few months that I took it.

Feeling like I had been cured, and definitely making headway on my dissertation, I stopped taking St. John’s Wort.  Cold turkey.  Just quit one morning, and tossed the bottle into the dumpster on my way to work.  Within a few days, I developed an absolutely crushing headache that lasted for several days, I began sweating profusely, and was nauseous.  I also developed a horrible tremor.  I had to leave work one day, I felt so awful.  Being young and stupid, it did not occur to me that I was going through withdrawal from the St. John’s Wort until I mentioned that I had stopped taking it to my mentor and she looked at me like I was a complete idiot, which she followed with a lecture on the dangers of withdrawal from anti-depressant medication.

So, do these herbal remedies really work?  As I mentioned, at the time, the general consensus was that they do not, that any beneficial responses that occur while taking it are due to a placebo effect.  My experience, both as I took it and when I quit taking it, however, would suggest that St. John’s Word does something, but I’m not willing to say, definitively, that it does since I could have experienced a placebo effect, or simply gotten better due to the passage of time.  Over the years, I’ve checked in on the literature with respect to St. John’s Wort, and it is still mixed, but the idea that it is an effective treatment for depression is gaining traction in the United States.  NIH’s National Center for Complementary and Alternative Medicine (NCCAM) still regards St. John’s Wort as no better than a placebo.  A recent systematic review of many studies by Klaus, Berner, and Levente (2009) suggest that St. John’s Wort is more effective than a placebo for treating symptoms of depression.  A list of studies over the last decade continue to produce a mix of results.

If St. John’s Wort does work (and I do not take the fact that it worked for me as definitive proof that it does), I would predict that it probably works much like prescription SSRIs, such as Prozac, work, by blocking reuptake of Serotonin, making more of that neurotransmitter available to synapses in the nervous system.  I will say that the withdrawal symptoms I experienced when I stopped taking St. John’s Wort match up almost perfectly with the symptoms of SSRI withdrawal.

So, the jury is still out on these medications, which is why, despite my story, I cannot advocate their use.  I strongly suspect that the reason behind the mixed results is that St. John’s Wort is being tested in these studies on a variety of levels of depression.  I am no expert on the subject, but I do not believe I was experiencing major depression when I began taking it.  I was depressed, undoubtedly, but I would not characterize my symptoms as extreme.  It may be, and this is pure speculation on my part so take it with a grain of salt, the effectiveness of St. John’s Wort may be as a treatment for low to moderate levels of depression, as a sort of weaker SSRI, rather than as something that can be effective against full-blown major depression.  I do not know for sure, but I will continue to check in on the literature about St. John’s Wort from time to time, just see what progress is being made.  These remedies serve to remind us that there are probably many such remedies for various ailments out there, in nature, either as part of local tradition, or waiting to be discovered.  But caution and research are also needed to make certain they are safe and effective.

Reference

Klaus, L., Berner, M., and Levente, K. (2009). St. John’s wort for major depression. Cochrane Database for Systematic Reviews, 4, DOI: 10.1002/14651858.CD000448.pub