Marked monoamine oxidase A deficiency is genetic and is often characterized by impulsive aggressiveness. This results in disruption of the breakdown of serotonin, epinephrine, norepinephrine, or dopamine. The gene encoding monoamine oxidase-A (MAO-A) is located on the X chromosome.
What is monoamine oxidase-A deficiency?
Monoamine oxidases represent enzymes responsible for the breakdown of monoamines. In this process, they are deaminated with the help of water and oxygen, producing aldehydes, hydrogen peroxide, and ammonia. Monoamine oxidases (MAO) include both monoamine oxidase-A and monoamine oxidase-B. Only monoamine oxidase-A breaks down the neurotransmitters serotonin, norepinephrine, epinephrine and melatonin. Monoamine oxidase-B mainly degrades benzylamine and phenethylamine. However, both monoamine oxidases equally control the deamination of dopamine, tryptamine and tyramine. In the case of a deficiency of monoamine oxidase-A, serotonin, melatonin, noradrenaline and adrenaline accumulate. This in turn can lead to behavioral changes toward aggressive behavior. A pronounced monoamine oxidase A deficiency is also known as Brunner syndrome. This syndrome was first described by Brunner in 1993 in a family whose members exhibited greatly increased monoamine levels in their urine and at the same time were conspicuous for aggressive behavior. In other psychiatric examinations of further persons in later years, however, no clear connection between monoamine oxidase-A and behavior could be established. What was special about Brunner’s studies was the complete absence of MAO-A. However, a study in 1995 of mice whose gene encoding MAO-A was knocked out showed increased serotonin levels, which correlated with anxious behavior in the young and aggressive behavior in the adults. After administration of serotonin inhibitors, their behavior returned to normal.
Causes
Monoamine oxidase-A is encoded by the MAOA gene, which is located on the short arm of the X chromosome. The exact gene locus is Xp11.3, and mutations of this gene can cause restriction or total loss of monoamine oxidase-A activity. Since men have only one X chromosome, such a mutation has a greater effect on them than on women. Thus, monoamine oxidase A deficiency would only occur in women if their two X chromosomes each contained a defective MAOA gene. This may partly explain why aggressive behavior is observed more frequently in men than in women. However, the studies showed that a deficiency in monoamine oxidase-A alone does not necessarily lead to violent and aggressive behavior. The circumstances of life are also decisive. It was found, for example, 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, however, individuals with defective gene who were not abused in their early youth did not necessarily become violent. It was only found that monoamine oxidase A deficiency increased the risk of criminal and aggressive behavior. Why there is increased aggressiveness and decreased empathy when serotonin, norepinephrine, and epinephrine are enriched requires further investigation, especially since serotonin, on the contrary, is known for its calming effects. However, as mentioned above, in mice, administration of serotonin synthesis inhibitors in the presence of monoamine oxidase A deficiency completely normalized the animals’ anxious and aggressive behavior.
Symptoms, complaints, 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, this is probably the tip of the iceberg. In many milder forms of monoamine oxidase A deficiency, there may be no symptoms at all because life circumstances are favorable.
Diagnosis and disease progression
The cause of monoamine oxidase A deficiency can be determined by genetic testing. For this purpose, a blood sample is taken, which is rendered uncoagulable with the help of EDTA.The MAOA gene on chromosome Xp11.3 is then examined for several 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. In these mutations, there is reduced synthesis of monoamine oxidase-A.
Complications
Not in every case does monoamine oxidase A deficiency necessarily have a negative effect on the patient’s health. In most cases, however, patients experience increased aggressiveness. This can have a very negative effect on the social environment of those affected and thus lead to exclusion. Especially in children, monoamine oxidase A deficiency can lead to severe developmental disorders, resulting in depression and other complications in adulthood. Quality of life is significantly reduced and limited by the condition. Likewise, children suffer from reduced intelligence, so that difficulties may arise at school. In many cases, parents are also affected by psychological distress or depression due to monoamine oxidase A deficiency. Treatment does not prove easy in every case. Not infrequently, those affected do not realize that they are suffering from aggression due to monoamine oxidase A deficiency and therefore refuse treatment. For this reason, it is primarily the parents and relatives of the affected person who are responsible for timely treatment. The treatment itself is carried out with psychotherapy and can lead to success. Life expectancy is usually not limited by monoamine oxidase A deficiency.
When should you see a doctor?
If children and adolescents show abnormalities and peculiarities of social behavior, a physician should be consulted. A characteristic feature of monoamine oxidase A deficiency is an aggressive demeanor on the part of the affected person, underpinned by impulsive behavior that is difficult to control. If parents or guardians are unable to exert sufficient calming influence on the child, the child will require medical assistance. If the complaints increase in the course of further development, a doctor should be consulted immediately. If the child shows violent behavior towards adults, other children or animals, this is considered a cause for concern. A doctor must be consulted so that a causal investigation and subsequent therapy can be initiated. Additionally, if the child comes from an environment where he or she has had an experience of violence, it is considered to be of additional risk. Help and support should always be sought as soon as problems arise in interpersonal relationships due to a violent 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 difficulty and without adequate communication, a visit to the doctor should be made. In many cases, it is not possible for those affected to resolve disputes calmly and through conversation.
Treatment and therapy
Causal therapy of monoamine oxidase A deficiency is not possible because the syndrome is genetic. Often, there is also no need for treatment because there is usually a lack of insight into the disease among those affected. If a mild form of monoamine oxidase A deficiency is present, there are often no symptoms at all. Then slightly increased aggressiveness can be counted as part of the normal spectrum of human behavior. It has been shown that favorable life circumstances can compensate for the effects of mild monoamine oxidase A deficiency. Accordingly, psychotherapeutic interventions can certainly lead to positive behavioral changes in conspicuous behavior. Psychotherapeutic approaches should also be used to try to attenuate aggressive behaviors in the more pronounced forms of monoamine oxidase A deficiency. There is not yet sufficient experience for drug treatments.
Outlook and prognosis
The outlook for a cure is poor. Patients suffer from a genetic defect that cannot be corrected according to current scientific knowledge. However, research on the genetic material is in full swing, which is why there is some degree of hope.Patients must therefore inevitably cope with restrictions in everyday life. Quality of life can suffer due to susceptible aggressiveness. In particular, the environment may 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. The aim is to respond preventively to triggers of emerging aggressiveness. This requires a high degree of discipline. It is to be expected that psychosocial therapy will curb the symptoms of the disease to such an extent that they no longer represent a hindrance in everyday life. Relaxation techniques such as yoga and autogenic training contribute to lasting freedom from symptoms. In addition, addictive substances should generally be avoided. Stress should also be avoided. With pronounced self-discipline, this results in a favorable prognosis. Alternatively, it can be assumed that the signs of monoamine oxidase A deficiency can be contained with medication. However, no scientific study of the success of specific drugs exists to date.
Prevention
Because monoamine oxidase A deficiency is genetic, it cannot be prevented. Only the expression of the effects in terms of behavior can be positively influenced by favorable life circumstances. This is particularly true for the mild forms of monoamine oxidase A deficiency. In Brunner syndrome, however, increased aggressiveness cannot be prevented but can be limited.
Follow-up
Affected individuals suffering from monoamine oxidase A deficiency do not always develop symptoms. In many cases, the disorder progresses inconspicuously with only mild behavioral abnormalities, which can also be explained by environmental influences. Therefore, follow-up is usually not necessary. Even in the most extreme form of the disorder, the Brunner syndrome, there is usually no aftercare, although longer-term psychotherapeutic care of the sufferers could certainly lead to a change in behavior here. However, most patients lack any insight into the disease. Therefore, they will not enter therapy on their own. Furthermore, there is hardly any experience as to which measures are at all promising. The number of known cases of monoamine oxidase A deficiency is too small for the development of a suitable therapy concept. However, in the case of extreme monoamine oxidase A deficiency, if serious criminal acts occur, an attempt can be made to develop long-term strategies for positive behavioral change together with the patient in the context of a prison sentence with preventive detention and subsequent placement in a psychiatric hospital. However, this requires the constructive cooperation of the person concerned. In particularly severe cases, the patient must remain permanently housed in a psychiatric facility because of his or her aggressiveness. So far, the only treatment available is psychotherapeutic therapy. In view of the sparse occurrence of cases of monoamine oxidase A deficiency, no experience is currently available for possible drug therapy.
What you can do yourself
People with monoamine oxidase A deficiency have a genetic defect. This cannot be cured with current options, either medically or by measures taken independently. Affected patients are comparatively often conspicuous for their aggressive behavior. If undesirable behavioral patterns are present, remedial action can be taken in the area of self-help through various options for behavioral regulation. In addition to participation in behavioral therapy, seminars offered for training in 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 behaviors. This promotes improved interpersonal interaction and heightens awareness of one’s own demeanor. In order to balance the inner stress experience, relaxation techniques have proven themselves in many cases. Through yoga or meditation, an inner balance is promoted. Through the establishment of an 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 on one’s own or by participating in courses. The person concerned is thus flexible in the application of the techniques and can act as needed when problems arise.In addition, a healthy lifestyle is advisable. A balanced diet and avoidance of toxins such as nicotine and alcohol promote well-being and contribute to improved health.
