Reactive aggression

The main factor in the first type of aggression is a deficit of serotonin in the brain, which leads to the fact that the brain cannot control emotional outbreaks.

In children with autism, the level of this neurotransmitter is elevated in the blood, which often leads to the erroneous conclusion that is is the same in the brain. However, serotonin levels have been shown to be significantly reduced in the brain. 

 

In one of the studies using MRI, healthy people with a normal level of serotonin and its deficiency were shown photographs of people with an aggressive face (which is suggested to increase the level of aggression in people who looks at these photographs). Using MRI, it was found that in people with a lack of serotonin, the connections between the part of the brain responsible for the emotional response, orbitofrontal cortex, and the rest of the sites were weaker than in people with a normal level. The authors explained that a lack of serotonin leads to the fact that the brain cannot control emotional outbreaks and so-called “emotional reactivity” takes place in the brains of the people with serotonin deficiency.

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Moreover, serotonin, like many other elements of the endocrine system, is directly interconnected with both the nervous and immune systems. Serotonin has been shown to regulate the functions of many immune cells: macrophages, natural killers and eosinophils.

 

Also, a derivative of serotonin is melatonin - a sleep hormone. It is known that many children with autism to one degree or another have problems with sleep - it is either insomnia or frequent awakenings at night or a very early rise (4-5 in the morning). Melatonin is synthesized from serotonin, so a deficit of serotonin in the brain in autism logically leads to a deficiency of melatonin too.

 

Causes of serotonin deficiency

There are two main reasons for the imbalance of serotonin: a mutation in the SERT gene, which is responsible for the production of this neurotransmitter, which occurs in an extremely rare percentage of cases of infection.

 

Infection does not directly affect this neurotransmitter - it is a complex process. Directly infection affects the synthesis of tryptophan - an amino acid that is involved in many immune, nervous and metabolic processes (there are more than 1000 of them). But what is important tryptophan is also a building block for serotonin.

 

 

The role of tryptophan

It has been shown in many studies that tryptophan deficiency or its impaired catabolism is often observed in children with autism. It has also been proven that infection during pregnancy leads to deficiency of tryptophan and serotonin in offspring. 

 

Tryptophan deficiency and catabolism disorders are hallmarks of chronic neuroinflammation triggered by viral infections (for a detailed discussion of this, see Mehraj and Routy. Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests). As a result of this, through catabolism of tryptophan, infections, and especially viral ones, lead to a deficiency of serotonin in the brain and its excess in the blood.

 

In addition, it has been shown that B cells (which have serotonin receptors on the surface to function correctly) infected with the Epstein-Barr virus have reduced serotonin uptake, which leads to impaired function of these important immune players. B cells produce antibodies and are responsible for both innate and acquired immunity. Since tryptophan itself and, to a greater extent, its various derivatives are important players in the immune system, the immune response, especially against some viral infections, is suppressed, which leads to the persistence of these infections.

 

Children with autism given tryptophan as a supplement showed less aggression, improved communication skills, reduced repetitive behavior, improved sleep (due to increased melatonin production) and enhanced learning skills.  The dosage of tryptophan, which is often used in studies involving children, is 6 mg/kg weight, divided into three to four doses at equal time intervals. However, this dosage may be gradually increased to up to 60 mg/kg of weight if well tolerated, according to some authors. 

 

Foods rich in tryptophan or other elements involved in the synthesis of serotonin include:

- Eggs

- Cheese

- Pineapples

- Tofu and other soy products

- Salmon

- Nuts and seeds (pumpkin and others)

- Turkey, duck and lamb meat

- Oats

- Beans

 

Also, one of the elements involved in the synthesis of serotonin from tryptophan is vitamin D. Therefore, for those children who have low levels of this vitamin, it is recommended to add this vitamin as an additive for the induction of serotonin.

 

Vitamin B6 and magnesium are also involved in the synthesis of serotonin, so the addition of these elements in the form of supplements or foods rich in them is also recommended.

 

As well as omega-3 fatty acid also participates in this metabolic pathway and as well as many other positive effects such as anti-inflammatory and immune-modulatory.

 

Some may ask why use tryptophan and not 5-HTP directly. The explanation is simple: 5-HTP will convert to serotonin very rapidly and will accumulate in the blood almost immediately, without bringing a positive effect, since accumulation in the brain will practically not occur

 

We do not exclude the possibility that some parents have already tried using tryptophan, omega-3 or vitamins B and D, but did not observe a significant effect. This can be explained by the fact that in the presence of even a latent infection, the effectiveness of the tryptophan scheme may not work since the infection will simply block the synthesis of serotonin.

 

Cold-blooded or dominant aggression

The second type of aggression, which occurs in some healthy children, but can also occur in children with autism. As an example of this type of aggression, there are often cases of aggressive behavior among siblings up to a certain age.

 

In this type of aggression, elevated testosterone is the main biological factor (but often in combination with low serotonin – see above)

 

Testosterone is predominantly male sex hormone, in men, the main production of testosterone is localized in Leydig cells in the testes. Half of the testosterone in women is produced by the ovaries, and the rest by the adrenal cortex. Testosterone biosynthesis occurs in other tissues, as well as in some areas of the brain.

Testosterone is a steroid hormone metabolized from cholesterol. In blood circulation, testosterone binds to sex hormone-binding globulin (SHBG), and is thus protected from metabolic degradation, but is also biologically inactive in this state. Only a small part of the hormone is free and active (able to bind to its receptor or undergo further metabolism).

 

Several studies have examined the relationship between salivary / plasma testosterone levels and aggression in people without autism, and contradictory results have been obtained.

 

Some of the studies do not describe a clear relationship between plasma/saliva testosterone levels and aggressive behavior in groups of children before adolescence, among male students and healthy adult men.

However, there are studies showing a strong positive correlation between testosterone (and testosterone precursor) levels in plasma/saliva and aggression (for example, in groups of male children with behavioral disorders, male and female adolescents, and adult and male prisoners).

 

One of the studies also measured plasma testosterone levels in nine patients with ASD compared with a group of neurotypical children. Nine adolescent children with ASD were divided into three groups consisting of (1) aggressive towards others, (2) with self-aggression, and (3) non-aggressive children with ASD. A group that was aggressive against others had higher testosterone levels than any of the comparison subjects.

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But most studies on the relationship between aggression and testosterone in general and in autism have contradictions.

These discrepant results may be due to several factors: 

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(1) involvement of other components of androgen activity – factors, other than total plasmatic testosterone levels - in modulating androgen activity (e.g., the function of enzymes responsible for the metabolism of testosterone, the sensitivity of androgen receptors, levels of active/free testosterone in plasma);

(2) involvement of other hormones in the etiopathogenesis of aggression in humans (cortisol, vasopressin, oxytocin, serotonin and others);

(3) existence of subtypes/ classes of aggression;

(4) limitations in the exact evaluation of aggressive symptoms.

 

In regard to the second point, it has been suggested that low levels of serotonin in combination with increased levels of testosterone with respect to cortisol may increase the aggression level in some. Thus, the neurobiological profile associated with low levels of cortisol, high levels of testosterone and low levels of serotonin may be prerequisites for aggression.

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The role of testosterone in this cycle is well described in a 2010 paper. The authors explain that there are still ambiguities in the mechanism of action of testosterone in relation to the induction of aggression. They could find a way to prove that in people with the weakened function of the orbitofrontal cortex, testosterone had a significantly more pronounced effect on increased aggression.

Impaired neural connections at this site are associated with low serotonin levels as was said above. That is, the impaired function of this cortex can be explained by a low level of serotonin in the brain.

 

Thus, the circle closes at a low level of serotonin and, thus we again return to infection because infection and inflammation in the brain were shown to be the most important factors in lowering serotonin levels.

What should be done to regulate serotonin levels was described above. How to treat infections and inflammation is explained here.

Supplements and products that can help lower testosterone levels:

• Low cholesterol foods (cholesterol is the building block for testosterone)

• Nuts

• Licorice root

• Flaxseed or flaxseed oil

• Omega-3

• Mint, aromatherapy using peppermint oil (possibly with the addition of lavender)

• Tofu and other soy products

To avoid:

• High cholesterol

• Excessive blood sugar because insulin produced in response to high sugar levels induces testosterone production