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Stress and Aggression P2

Serotonin is tied to the tryptophan pathway, and we’ll be talking about this tomorrow.  When we have chronic bacterial infection, it causes the breakdown of tryptophan which diverts our tryptophan and affects our serotonin levels.  In addition, if we have inadequate levels of BH4, we don’t have the BH4, and we need to convert thee tryptophan to serotonin.  So, again, all the pieces are coming together, and if we have all of these factors in play, we’re more likely to have problems with serotonin levels that impact mood as well as aggressive behavior.

Catecholamines, serotonin and dopamine, and the role of COMT and MAO-A.  These systems are very well known to be involved in the regulation of aggression.  So, again, keeping in mind your COMT status, your MAO-A status, watching the intake of methyl donors for those that are COMT++.  One of points I noticed was a lot of new people get confused one is yes there may be methylation cycle mutations.  So, in general, you would think you need more methyl donors, but if you’re COMT++, we look to supplement that pathway without directly adding too many groups.  So, look toward hydroxyl-B12 than methyl B12 so that we don’t trigger aggressive mood swings.

Part of the reason we see some of this is serotonin as well as dopamine have negative feedback inhibition and auto inhibition. If the serotonin levels get too high, they will feedback and inhibit themselves so they will drop too low just as we see with too much dopamine.  Because the dopamine will be higher if you’re COMT++, it can feedback and inhibit itself, and it’s the mood swings that create the issues.  Someone who would be COMT- – and MAO- – is going to be much more even all of the time.  If we have COMT++, MAO++, and on top of that, we’re layering detox, it’s part of the reason we see the mood swings and aggressive behavior.  Again, just the role of COMT and MAO polymorphisms in aggression.

Just a side note:  Those of you who have dabbled in cigarette smoking in the past, part of the reason people are attracted to it is it does inhibit MAO-A.  So, it’s going to temporarily increase your serotonin levels and make you feel better.  Again, inhibition of MAO-A will cause aggressive behavior.  So, in the long term, it’s not a great idea.

Again, back to nitric oxide which we were talking about earlier.  Again, we see the same mediators and the same pieces coming together in different ways all the time. There’s an interactive activity between nitric oxide and serotonin.  So, when we see mutations that pull down the level of nitric oxide too low, it actually causes elevated and sustained aggressive behavior.  Again, everything in moderation.  We don’t want nitric oxide too high.  It will deplete certain mediators.  It has negative effects, but if it gets too low, we’re going to have aggressive behavior. The same thing is true when it comes to serotonin.  Try to use small amounts overtime so that we keep the levels much more even.

So, a lack of nitric oxide can cause aggressive behavior, and we already talked about the relationship between nitric oxide synthase and BH4 levels and also a lack of 5HTP receptor function can play a role.  So, balance and moderation, whether we’re talking about BH4, NOS, or serotonin.

Balances in dopamine and dopamine receptors will play a role in aggressive behavior.  If the dopamine is fluctuating all over the place, we’re going to see mood changes.  The relationship between this membrane fluidity that I keep talking about and the ability of the dopamine receptor to move in a fluid membrane and that we need methylation for that.  The role of 5-methyl THF and SAMe in keeping this system functioning as well as SAMe directly to keep histamine levels in balance so that we’re not keeping this inflammatory aggression cascade.

There is actually a tie in between altruism and risk taking behavior, and the type of snip that you have or what’s going on at the D4 receptor as well as balances with respect to attention.  So, certain polymorphisms, certain snips of certain bases, related to dopamine seem to play a role when it comes to altruism.  Again, back to that same D4 receptor that Dr. Deep’s working on.  The opposite snip might create the opposite behavior and altruism which would fit in with some of what we see with aggression and non-ideal behaviors.

In order to get the binding and the changes that we need in that dopamine receptor, again, we need GTP.  GTP is generated by the methylation cycle or supporting with nucleotide bases, and the other types of receptors in the membrane utilize protein kinase C which, again, is tied together with aggression.

This is one we talked about earlier today, the need for a methyl transferase and methyl groups in order to have the appropriate signaling in that pathway.  Again, looking at the role that the methylation cycle, methionine synthase, as well as membrane fluidity has in the ability to move these methyl groups around on dopamine receptor function.  If this isn’t functioning properly, we get imbalances in the dopamine signaling pathway.  It can play a role in aggression as well as attention and learning.

I’ve mentioned before this imbalance between dopamine and norepinephrine. If the norepinephrine levels are too high relative to dopamine, we sometimes see attention issues, and the shortcut pathway through the BHMT enzyme is going to make more norepinephrine relative to dopamine.  So, in some of those cases, we can look at the attention formula, look at SAMe, look at DMG to try to get this pathway in better balance because norepinephrine as well as epinephrine can react at that same receptor as dopamine.

So, again, dopamine has been implicated as having strong role in aggressive behavior.  When we look at increased rates of schizophrenia and violence, they are very related to dopamine dysfunction.  So, if we’re having problems with dopamine levels because of the inability to have signaling act as we would like to in those fluid membranes, it will play a very strong role with potential aggression problems and imbalances in behavior.

So, what we find is that violent population increased norepinephrine metabolites.  So, again, we want an appropriate balance between dopamine, norepinephrine, and adrenaline.  Adrenaline’s going to be signaled by the fight or flight response, the cortisol pathway, and cortisol levels play a roles here, too.  So, while cortisol doesn’t have a direct effect on aggressive behavior, it has a moderating effect that plays a role tied in with testosterone levels.

So, if we go back to the slide where we talked about the ACE deletion and the ACE deletion will help you to break down bradykinin so you’re not triggering aggression through bradykinin, but the ultimate end point with the increased conversion from angiotensin I to angiotensin II is that we end up with higher levels of aldosterone.  Aldosterone is going to compete with cortisol.  So, having those ACE deletions may give you less bradykinin but more problems in the calming effect of cortisol.  So, low levels of cortisol are also tied to aggressive behavior. This is a segway into the whole stress talk because cortisol is very related to the whole fight or flight response and stress reaction.  So, being under chronic stress, whether it’s physical stress from detox or emotional stress from having your child detoxing all the time, is tied right in with aggressive behavior and imbalances in this pathway.

Now, this, I thought, was a lovely analogy.  It was sent to me by one of the parents, and what that parent was saying was what phosphatidyl serine does which helps to keep the cortisol response in balance does for the body is to help the body to be more sensitive to cortisol.  Cortisol is a hormone that is secreted in response to stress.  So, cortisol helps to keep the stress response under control. If a child is constantly having their chemistry thrown out of balance, they’re going to have high levels of norepinephrine and other fight or flight hormones in their system.  They’re walking around in a state of constant stress, and their body can’t compensate.   So, you may read that cortisol causes stress, but it’s actually the opposite.

Stress is a sign that this person has been under stress for a long time, and the constant levels of this create a situation where the cortisol is no longer effective. What I really liked was this parent’s analogy to what happens with insulin and type II diabetes because there, the body is no longer sensitive to insulin. What he’s proposing is when you’re under constant stress, you’re no longer sensitive to cortisol and its modulating effects.  That’s why we look at phosphatidyl serine not just to feed into our methylation pathway and to help with membrane fluidity but also to help us be more sensitive to this cortisol response so that you don’t wear out your ability to produce cortisol and end up with adrenal burnout.

The tie in between hormones and stress and aggression is really a vicious cycle.  So, we can look at this feedback response between the stress response and the aggression systems in the body.  Stimulating aggression leads to higher stress hormones, and activating the aggression system plays a role on the stress response.  So, you end up in this cycle of stress and aggression.

What we’re talking about when I talk about stress and aldosterone is two molecules in the body that look very, very similar.  What happens is that there’s only one receptor that binds both of them.  So, they’re both competing for the same receptor. In order to get cortisol to bind, we need lower amounts of aldosterone, but if we have ACE deletions, we end up with a lot of aldosterone relative to cortisol. So, the modulating effects of cortisol are not as effective on the system with ACE deletions.  The other thing I want to mention is that there’s an enzyme in the body that will play havoc with this system, and using too much licorice can have negative consequences on this system.

So, what is stress?  Well, distress is what we’re talking about, and it’s a state in which an animal cannot escape from or adapt to the internal or external stressors or conditions it experiences, resulting in negative effects of well-being.  Again, this is really what all of you in this room are in all the time, not just your children.  I alluded to earlier to earlier today that genetics come from somewhere, and if you’re seeing some of these mutations in your children, consider supporting yourselves because my guess is all of you are operating under distress all the time.  You have some of these mutations in your pathway.  So, just as when you’re on an airplane and they tell you to put your oxygen mask on before you put the one for your children, I know you can’t really do that.  You have to get your kids well before you can work on yourselves, but try to do a little something for yourselves so that you don’t burn out.

The stress response is a very old response.  It’s back from we were going to chase after dinosaurs or run from dinosaurs.  That’s why it’s fight or flight response, but the problem is that it was designed to protect you from animals in the wild.  Your body really can’t tell the difference between stress from a wild animal or stress from being up all night because a child is detoxing, and your system feels the same way and needs to address it.  While acute stress actually does some positive things for your system, long term chronic stress can be debilitating.  So, we want to occasionally have that acute burst of adrenaline, but what we would like to do is stay away from the chronic stress in the body whether it’s chronic viral infection, chronic bacterial infection, chronic emotional stress, chronic physical stress.

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