A pronounced monoamine oxidase A deficiency is genetically determined and is often characterized by impulsive aggressiveness. This disrupts the breakdown of serotonin, adrenaline, noradrenaline or dopamine. The gene encoding monoamine oxidase-A (MAO-A) is located on the X chromosome.
What is monoamine oxidase A deficiency?
Monoamine oxidases are enzymes responsible for breaking down monoamines. These are deaminated with the help of water and oxygen, resulting in aldehydes, hydrogen peroxide and ammonia. The monoamine oxidases (MAO) include both monoamine oxidase A and monoamine oxidase B. See nonprofitdictionary for Fatal Familial Insomnia (abbreviated as FFI).
Only monoamine oxidase A breaks down the neurotransmitters serotonin, noradrenaline, adrenaline and melatonin. Benzylamine and phenethylamine are primarily degraded by monoamine oxidase B. However, both monoamine oxidases equally control the deamination of dopamine, tryptamine, and tyramine. With a lack of monoamine oxidase A, serotonin, melatonin, norepinephrine and adrenaline accumulate.
This in turn can lead to behavioral changes towards aggressive behavior. A pronounced monoamine oxidase A deficiency is also known as Brunner’s syndrome. This syndrome was first described by Brunner in 1993 in a family whose members had greatly increased monoamine levels in their urine and at the same time became conspicuous through aggressive behavior.
However, other psychiatric studies of other people in later years could not establish a clear association between monoamine oxidase A and behavior. What was special about Brunner’s investigations was the complete absence of MAO-A.
However, a 1995 study of mice whose gene encoding MAO-A was knocked out showed elevated levels of serotonin that correlated with fearful behavior in the young and aggressive behavior in the adults. Her behavior returned to normal after she was given serotonin inhibitors.
Monoamine oxidase-A is encoded by the MAOA gene, which is located on the short arm of the X chromosome. The exact gene location is Xp11.3. Mutations in this gene can result in reduced or total loss of monoamine oxidase A activity. Since men only have one X chromosome, such a mutation affects them more than women.
In women, for example, a monoamine oxidase A deficiency would only occur if both of their X chromosomes contained a defective MAOA gene. This may also partly explain why aggressive behavior is observed more frequently in men than in women. However, the studies were able to prove that a lack of monoamine oxidase A alone does not have to lead to violent and aggressive behavior.
Living conditions are also important. It was found that abused boys with this defective gene often became violent later on. If this gene is not mutated, adverse living conditions do not automatically lead to violent behavior. On the other hand, people with the defective gene who were not abused in their early youth did not necessarily become violent.
It was only established that the risk of criminal and aggressive behavior was increased by a monoamine oxidase A deficiency. Further investigations are needed into why increased aggressiveness and reduced empathy occur when serotonin, noradrenaline and adrenaline accumulate, especially since serotonin is known for its calming effect.
As already mentioned, however, the administration of serotonin synthesis inhibitors in mice with a monoamine oxidase A deficiency completely normalized the anxious and aggressive behavior of the animals.
Symptoms, Ailments and Signs
In the case of a pronounced monoamine oxidase A deficiency, i.e. the complete absence of MAO-A, the situation is clear. The main symptom is impulsive aggressiveness, which can lead to violence, even in childhood. Furthermore, a slight intellectual deficit is recognizable.
In addition, the affected person is characterized by a pronounced emotional coldness. However, that’s probably the tip of the iceberg. Many milder forms of monoamine oxidase A deficiency may not have any symptoms at all because of favorable living conditions.
Diagnosis and course of the disease
The cause of monoamine oxidase A deficiency can be determined by a genetic test. For this purpose, a blood sample is taken, which is made non-coagulable with the help of EDTA. The MAOA gene on chromosome Xp11.3 is then screened for multiple mutations. On the one hand, there is a point mutation with a premature stop codon, which leads to the termination of monoamine oxidase A synthesis.
On the other hand, there are mutations characterized by multiple repeats (3 to 5) of a sequence in a polymorphic region of the gene. These mutations result in reduced synthesis of monoamine oxidase A.
A monoamine oxidase A deficiency does not have to have a negative effect on the health of the patient in every case. In most cases, however, the patients become more aggressive. This can have a very negative effect on the social environment of those affected and thus lead to exclusion.
Especially in children, the monoamine oxidase A deficiency can lead to severe developmental disorders, so that depression and other complications can occur in adulthood. The quality of life is significantly reduced and limited by the disease. The children also suffer from reduced intelligence, which can lead to difficulties at school.
In many cases, the parents are also affected by psychological problems or depression as a result of the monoamine oxidase A deficiency. Treatment is not always easy. It is not uncommon for those affected not to realize that they are suffering from aggression due to the monoamine oxidase A deficiency and therefore refuse treatment.
For this reason, the parents and relatives of those affected are primarily responsible for timely treatment. The treatment itself takes place with psychotherapy and can lead to success. Life expectancy is usually not reduced by monoamine oxidase A deficiency.
When should you go to the doctor?
If children and adolescents show abnormalities and peculiarities of social behavior, a doctor should be consulted. A characteristic feature of monoamine oxidase A deficiency is an aggressive appearance by the affected person, which is underpinned by impulsive behavior that is difficult to control. If parents or legal guardians cannot sufficiently calm the child, the child needs medical help.
If there is an increase in symptoms during the further development process, a doctor must be consulted immediately. If the child exhibits violent behavior towards adults, other children or animals, this is considered to be of concern. A doctor must be consulted so that the cause can be investigated and subsequent therapy can be initiated.
If the child also comes from an environment in which it has experienced violence, it is considered to be an additional threat. Help and support should always be sought as soon as problems arise in interpersonal relationships due to physical interaction.
If the affected person has weak impulse control, is easily provoked by everyday challenges, or reacts particularly intensely to life events, this is considered unusual. If conflicts can only be resolved with particular effort and without adequate communication, a doctor should be consulted. In many cases, it is not possible for those affected to settle disputes in peace and through a conversation.
Treatment & Therapy
A causal therapy for monoamine oxidase A deficiency is not possible because the syndrome is genetic. There is often no need for treatment either, because those affected usually lack insight into the disease. If there is a mild form of monoamine oxidase A deficiency, there are often no symptoms at all.
Then a slightly increased aggressiveness can be counted towards the normal spectrum of human behavior. Favorable living conditions have been shown to offset the effects of mild monoamine oxidase A deficiency. Accordingly, psychotherapeutic measures in the case of conspicuous behavior can certainly lead to positive behavioral changes.
Even in the more severe forms of monoamine oxidase A deficiency, attempts should be made to use psychotherapeutic approaches to alleviate aggressive behavior. There is still insufficient experience with drug treatments.
Outlook & Forecast
The prospect of a cure is slim. Patients suffer from a genetic defect that cannot be corrected according to current scientific knowledge. However, research on the genome is in full swing, which is why there is a certain degree of hope. Patients must therefore inevitably come to terms with limitations in everyday life. The quality of life can suffer due to the prone aggressiveness. In particular, the environment can feel disturbed, which contributes to social problems. On the other hand, there is no reduction in lifespan.
Patients with monoamine oxidase A deficiency require long-term behavioral therapy and control. It is about reacting preventively to triggers of emerging aggressiveness. This requires a high level of discipline. It can be expected that psychosocial therapy will reduce the symptoms of the disease to such an extent that they no longer pose a handicap in everyday life. Relaxation techniques such as yoga and autogenic training contribute to long-term freedom from symptoms. In addition, addictive substances should generally be avoided. Stress should also be avoided. With a pronounced self-discipline, there is a favorable prognosis.
Alternatively, it can be assumed that the signs of monoamine oxidase A deficiency can be curbed with medication. However, to date there has been no scientific study on the success of certain medicines.
Since monoamine oxidase A deficiency is genetic, it cannot be prevented. Only the extent of the effects in terms of behavior can be positively influenced by favorable living conditions. This is especially true for the mild forms of monoamine oxidase A deficiency. In the case of Brunner’s syndrome, however, increased aggressiveness cannot be prevented, but it can be limited.
Those affected who suffer from monoamine oxidase A deficiency do not always develop symptoms. In many cases, the disorder is unobtrusive with only slight behavioral abnormalities, which can also be explained by environmental influences. Therefore, follow-up care is usually not necessary. Even in the most extreme form of the disease, Brunner’s syndrome, there is usually no follow-up care, although long-term psychotherapeutic care of the patient could definitely lead to a change in behavior.
However, most patients lack any insight into the disease. Therefore, they will not seek therapy on their own. Furthermore, there is hardly any experience as to which measures are promising at all. The number of known cases of monoamine oxidase A deficiency is too small to develop a suitable therapy concept.
However, if serious criminal offenses occur in the case of an extreme monoamine oxidase A deficiency, a prison sentence with preventive detention and subsequent placement in a psychiatric hospital can be used to try to develop long-term strategies for positive behavior change together with the patient.
However, this requires the constructive cooperation of the person concerned. In particularly severe cases, the latter must remain permanently in a psychiatric facility due to his aggressiveness. So far, only psychotherapeutic therapies have been available for treatment. In view of the few cases of monoamine oxidase A deficiency that occur, there is currently no experience of possible drug therapy.
You can do that yourself
People with monoamine oxidase A deficiency have a genetic defect. With the current possibilities, this can neither be cured medically nor by measures taken independently.
Affected patients often show aggressive behavior. If undesired behavioral patterns are present, there are various ways of regulating behavior that can be remedied in the area of self-help. In addition to participating in behavioral therapy, seminars offered for training anti-aggression can be found helpful. Participants learn step by step how to react better to different stress triggers in everyday life and train possible optimized behavior. This promotes improved interpersonal interaction and raises awareness of one’s own appearance.
Relaxation techniques have proven effective in many cases to compensate for the inner stress experience. Yoga or meditation promotes inner balance. Through the creation of inner harmony and the reorientation of perception, an improvement in the quality of life can be observed in many people. The methods can be used independently or by participating in courses. As a result, the person concerned is flexible in the application of the techniques and can act as needed when problems arise.
In addition, a healthy lifestyle is recommended. A balanced diet and the avoidance of toxins such as nicotine and alcohol promote well-being and contribute to improved health.