Adult neurogenesis
The creation of new neurons, known as neurogenesis, is an important process. It is by this process that the brain forms, and most of it occurs during pre-natal development. An early theory proposed by neuroanatomists that has recently been refuted by experimental evidence is that adult neurogenesis does not occur. In adult neurogenesis, it has been observed that most of the new neurons die shortly after their formation, while only a few become integrated into the functioning structure of the brain. So what is the significance of adult neurogenesis?
While the functioning of this process is not known, it has been speculated that it is important for memory and learning processes, and is linked to stress. Stress causes a lot of people a lot of harm, and has been linked to many disorders, such as depression. Depression is a condition that is regulated by antidepressants. Know what other activity is regulated by the activity of antidepressants? You guessed it, NEUROGENESIS! A recent study showed that the brain responds to stress-relieving situations, such as those that build learning and memory, with increased neurogenesis. Stressful situations, such as those that induce physiological or psychological stress, are marked by decreased neurogenesis. A decrease in neurogenesis has been indicated to be a key factor in the progression of depression.
Of course, there are individuals out there who have reported experiments that refute the process of adult neurogenesis. One author speculates on whether or not there is true scientific evidence to back these findings, and that perhaps the new cells being formed are glial cells.
So, how can one keep the level of neurogenesis up and reduce depression? By removing oneself from physiologically and psychologically stressful situations, and getting some exercise.
“So, how can one keep the level of neurogenesis up and reduce depression? By removing oneself from physiologically and psychologically stressful situations, and getting some exercise.”
For once I’d love to see “drink heavily, play computer games and eat all the junk food you can stand” but no, it’s always about getting some exercise…
Are you talking about situational depression or Bipolar/Unipolar disorders (which may include schizo-affective disorders, cyclothemia and a host of other neurotransmitter aberrations)?
There is a difference between depression linked to predominantly environmental causes and those endemic to genetic/biological factors even though stress exacerbates all forms of depression – just as there are differences in diabetes mellitus type II, diabetes mellitus type I and gestational diabetes with insulin resistance common to all.
Many Bipolar/Unipolar sufferers find that most antidepressants either don’t work, lose effectiveness, or have cognitive side effects that are as bad or worse than the disorder.
Yes, excercise helps but it is in no way a panacea. If that were true, there would be no depressed athletes…
Adult neurogenesis, if true, would, I think, be considered a so-called paradigm shift. It reminded me of a recent paper in Nature on experiments done with a certain breed of double strand RNA. Also a paradigm shift. The authors had a helluva time publishing it because of the high bar the journal set for such controversial results.
Chemical Compound Found In Tree Bark Stimulates Growth, Survival Of Brain Cells
Most new antidepressents of the SSRI or SNRI class affect Serotonin or Noradrenaline (or both) levels or receptor sensitivity (nobody quite knows for sure). Dopamine manipulation is frowned upon and Glutimate manipulation shows some promise but has been ignored so far. Dopamine, the pleasure neurotransmitter would be the obvious choice to fiddle with but it can produce terrible consequences (see crystal meth, amphetamine salts, and crack cocaine abuse) as well as hypomania or even full blown mania (see Andrea Yates)*
The major problem here is the actual mechanism that is responsible for clinical depression/suicidal ideation. Manipulation of neurotransmitters with meds can be like trying to fine tune a radio with a jackhammer, there is almost always collateral damage.
*(Mrs Yates’ mania seems to be naturally occuring and not the result of speed or crack)
Are you actually making yourself any smarter through neurogenesis? Conversely, are depressed people any dumber?
Wellbutrin is an antideressant that is a dopamine and noradrenaline reuptake inhibitor, but one of the side effects can be mania or seizures.
Maybe it would depend on the area of the brain you are using. So Stress might aid neurogenisis in the amygdala while inhibiting it the hippocampus, and the other way round if the parasympathetic nervous system is activated.
I’m no expert by any stretch of the imagination, but from the limited amount of things I’ve seen…
Many of the benefits of ‘less stress’ are just as well explained by the resolution of a stress. This makes much more sense to my intuition actually. It doesn’t seem to me that avoiding stress is in and of itself a good thing. Stress produces responses which are downright beneficial, and seems to initiate strong learning responses… though it does appear more and more likely that a resolution of the stress is a critical aspect to that too.
Just putting it out there. There are lots of implications to the idea, and I’d love to see some testing of it. Of course, it would be ‘nice’ if stressful challenges that are overcome (or otherwise resolved) were a good thing… so there is some intrinsic bias there.
I should tell my Ph.D adviser that he’s making me dumber when he gives me so much work to do.
Lua Yar,
thanks. This is fascinating; and, for me, in a very personal way. I’ve been plagued by periodic depression over much of my adult life, and emerged from my most recent episode only a few months ago. Recently I began exercising again (not for reasons of mental health, but simply because I have got too fat). This new information will, I suspect, have a strongly reinforcing effect on my willpower when it’s 6 am, cold and rainy and the gym cruelly beckons…
Jsn @5, 2d para:
you’re right, hitting on a proper regime of meds is like trying to sew on buttons while wearing oven mitts. They don’t always help, and can do worse than merely not helping. But often they do help, and doctors are getting better at making them do so. I owe my life — and possibly not in a merely metaphorical sense — to cipralex and sulpiride.
Along with Travc, I find that a temporary stressful situation can indeed increase my learning. It ties in with some of the modes of learning that I was taught (granted this was a few years ago): multi-sensory stimulation, ties to a strong emotional response with interaction with the limbic system, and repetition, repetition, repetition. That “mantra” was repeated often in class, usually with a loud book slamming, or a flash of light or a picture on the PowerPoint screen, depending on circumstance, thus using all three of the modes. It instilled an urge to yell “there are five lights!”, but I do remember it.
I am wondering if a stressful situation might yield enough of the repetition (often stressful) and ties to an emotional response that the stressful situation may yield good long term learning.
So the question, then, is “is learning an inherently neurogenic event, or will synapse reinforcement and pathway streamlining be more likely?”
Of course all learning cannot be a neurogenic event, even if long term. But can stress, if not chronic actually increase neurogenesis?
My training in microbial ecology often asserts itself, and I recognize a bit of the intermittent disturbance hypothesis cropping up here. Might it apply?
(to Lua specifically: nice post, and based on my reaction and the other posts, nicely thought-provoking. Good work.)
Mrs Tilton,
Of course I would advocate that anyone who succumbs to the insidous effects of depression seek help. Lithium, SSRIs, SNRIs, and/or MAOIs, do a lot of good for people for a good number of people. Seroquel, Risperdal and a host of other antipsychotics are very necessary for those with dementia who fall under the clinical depression umbrella too.
ECT(electro Convulsive Therapy) has been refined and is still used for those who find no meds seem to help (No more Nurse Ratchet). Google “Electro Boy”
TMS (Transcranial Magnetic Stimulation) is akin to the same treatment that scientists have been using to stimulate areas of the brain to provoke “out of body” sensations and extreme “religious euphoric” response.
Lua,
Many adults with depressive illness have been also been diagnosed with ADD, which has something to do with faulty circuits in the prefrontal cortex. Many of these patients have been treated with Adderall (a mix of amphetamine salts; speed for lack of a better word) and find that they not only gain greater concentration but their depression is relieved. Hmmmmmm
“Along with Travc, I find that a temporary stressful situation can indeed increase my learning.”
As everyone knows, they can remember where they were when Kennedy was killed or on 9/11. So in that sense it can really help learning.
sailor,
Exactly. How that relates to neurogenesis, if at all, is an interesting question.
“Exactly. How that relates to neurogenesis, if at all, is an interesting question.”
Mike I have no idea, but you can see the adaptive value of remembering what triggers a massive adrenalin rush, so you don’t make the same mistake twice. The human problems seem to come because we trigger anxiety for mudane things like bills, for which flight and fight does not often work. So the learning would probably be aided in the the short term and go to hell over the long term. But under stress we may be strenghtening connections and even aiding neurogenesis to emotional parts of our brain, just to make sure we will get more and more anxious over the years.
No, no, no, you’re supposed to end with a toll free number where for just 39.99 I can get a bottle of pills that will increase my neurogenesis while allowing me to loose weight in my sleep.
Earlier this year I made a BBC radio programme about adult neurogenesis — it does, undoubtedly happen, but only, so far as we can tell, in the hippocampus. It’s not clear what the link to depression is, though it is also clear that there is such a link. Whether it is cause or correlation no one knows.
In any case, we interviewed most of the major players in the field — Liz Gould, who found it in rats as a post-grad, Barry Jacobs, who seems to think it’s the answer to everything, Jonas Fris&ecaute;n, who proved most elegantly that it doesn’t happen in the human cortex. There is also a bonus splash of Buffalo Springfield.
Anyone who wants an mp3 can write to me at seatrout punctuation gmail punctuation com; it’s about 30 minutes.
sailor,
Great, now I’m worried about making more worrying neurons by worrying…
I’m also dissapointed to learn I can’t simply run away from my mortgage.
MikeG. the upside is if you can find anything to do that is fun and makes you forget worrying, that might start a cycle the other way round. Also a small amount of worry can be great – give you energy and keep you on your toes, it is only when it become overbearing it is a poblem. The other thing is if we get a full blown anxiety, if it is possible convert it to motion – run or climb a mountain, that is what the physiological changes are equipping us to do.
Also you can run away from your mortgage, it might be great for your body and soul, but you generally loose the house.
Some of my recent blogs relate directly to this, specifically to the Andrea Yates effect which I think is directly explained by evolutionary physiology, and is a predictable “feature”. Yes, infanticide under conditions of extreme stress is a “feature”, a “feature” that essentially all mammals exhibit. Because mammals lactate, infants derive metabolic sustenance from the mother. What will happen if there are insufficient metabolic resources to sustain lactation? If the mother dies, the infant will die too. If the infant dies before the mother’s health is destroyed by starvation, she may recover and reproduce again if environmental conditions improve (lack of food was probably the major metabolic stressor over evolutionary time). If the state of metabolic stress is going to be prolonged, that is, longer than the time for the infant to mature and become self-sustaining in food supply, then the sooner the infant is killed, the fewer resources “go to waste” sustaining a useless cause, and the sooner a new pregnancy can be started (the first trimester takes very little additional metabolic resources). So I think that postpartum psychosis and infanticide is a “feature” to shed metabolic load and allow reproduction in the future.
So how about depression? Under acute and life threatening stress, such as running from a bear, the body invokes a state of euphoria where people can actually run themselves to death and feel good about it, the “runner’s high”. I think that is what stimulants of abuse do, they invoke the euphoria of extreme metabolic stress, which is why all the long term symptoms of stimulant abuse (cocaine heart, amphetamine mouth, brain damage), are similar to other degenerative diseases. The both result from a shut-down of normal repair mechanisms to conserve ATP for immediate consumption to “run from a bear”. I detail this in my blog on the placebo effect.
If an organism is going to run from a bear, while ignoring damaged muscles, strained tendons, broken bones, bleeding and other painful injuries, euphoria must be induced, pain must be suppressed, and the delusion that one is not tired and can successfully flee from and/or fight the bear (and win) must be invoked. If an organism could reach such a state of euphoria easily, all organisms would do so, and would quickly die. There must be an aversive state between the “normal” state, and the euphoria of extreme metabolic stress. I hypothesize that this is what depression is, a mild aversive state from mild metabolic stress to prevent organisms from entering the euphoric state of extreme metabolic stress without good reason.
I think that one thing that shifts from the “normal” state to the “fight or flight” state is the NO level. Stress is a low NO state (to disinhibit cytochrome oxidase and maximize potential ATP production). It ends up being a low ATP state (to turn off all non-essential systems (including neurogenesis), to paraphrase Rumsfeld “you go to war with the neurons you have, not the neurons you wished you had”.
To “fix it”, you need to raise the basal NO level which skews physiology more into the rest and repair state. I know of only 3 ways to do that:
1. meditation (such as the Dalai Lama does)
2. eat high nitrate foods such as green leafy vegetables. and/or
3. have the right biofilm of autotrophic ammonia oxidizing bacteria (patent pending not yet commercially available).