Attention deficit hyperactivity disorder (ADHD) produced by DAO deficiency

DR Healthcare has found that approximately 80% of children with ADHD also have a shortfall congenital defect of DAO activity, so that metabolize insufficiently histamine swallowed, turning it to the blood.
Trastorno de déficit de atención e hiperactividad (TDAH) ocasionado por déficit de DAO

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Attention Deficit and Hyperactivity Disorder (ADHD): nature and symptom picture

Attention Deficit and Hyperactivity Disorder (ADHD) is a disorder that is more prevalent in children and that is associated with an increase in motor activity and a decrease in the attention. It is a behavioral syndrome with neurobiological basis and has a strong genetic component. It is a very prevalent disorder that affects between 5 and a 10% of the adolescent population, being about 3 times more frequent in males. Have not been demonstrated differences between different geographic areas, cultural groups, or socioeconomic levels. Represents between 20 and 40% of consultations in the services of child and adolescent psychiatry.

This is a neurological disorder of the behavior characterized by the distraction moderate to severe, short attention spans, restlessness, motor, emotional instability and impulsive behavior. Although initially was recognized in children, has been recognized as a chronic nature, since it is still present and manifests itself beyond adolescence. Long-term studies have shown that between 60 and 75 % of children with ADHD continue to present symptoms in adulthood.

The main features of ADHD are, on the one hand, the difficulty to sustain the concentration (attention deficit disorder), especially under the circumstances that offer low stimulation and, on the other hand, the lack of inhibition or cognitive control on the impulses, often associated with concern to motor hyperactivity-impulsivity. These two sets of signs may occur separately or in combination.

The symptoms of ADHD fall into three groups:

– Lack of attention (neglect)

– Hyperactivity

– Impulsive behavior (impulsivity)

Some children with ADHD primarily have the type of disorder of lack of attention. Others may have a combination of several types. Those children with the type of disorder of lack of attention are less disturbing and is more likely than not being diagnosed with ADHD.

Lack of attention

– Fails to careful attention to details or makes careless mistakes in schoolwork.

– Has difficulty sustaining attention in tasks or games.

– Does not seem to listen when spoken to him/her directly.

– Do not follow instructions and fails to finish schoolwork, duties or obligations in the workplace.

– Has difficulty organizing tasks and activities.

– Avoids or dislikes engage in tasks that require ongoing mental effort (such as schoolwork).

– Often loses toys, school assignments, pencils, books or tools necessary for tasks or activities.

– Easily distracted.

– Often forgetful in daily activities

Hyperactivity

– Play with hands or feet or squirms in his seat.

– Leaves his seat when what is expected is that sit.

– Runs and climbs excessively in inappropriate situations.

– Has difficulty playing silently.

– Often talks excessively, this “in motion” or acts as if “driven by a motor”.

Impulsive behavior

– Produces answers before they finished listening to the question.

– Find it Difficult to wait their turn.

– Interrupts or intrudes on others (breaks into conversations or games).

Diagnosis of Attention Deficit and Hyperactivity Disorder (ADHD)

Too often, difficult children are incorrectly classified as children who suffer from Attention deficit hyperactivity disorder and, on the other hand, many children who truly do remain without diagnosis. In either case, are often overlooked the difficulties associated with the learning disabilities or mood problems. The American Academy of Pediatrics, (AAP) has issued guidelines to bring more clarity to this issue.

The diagnosis is based on very specific symptoms that must be present in more than one scenario:

– Children should have at least 6 attention symptoms or 6 symptoms of hyperactivity and impulsivity, with some symptoms are present before the age of 7 years.

– The symptoms must be present for at least 6 months, be observed in two or more scenarios and not be caused by another problem.

– The symptoms must be severe enough to cause significant difficulties in many settings, including the home, school and peer relationships.

The child must undergo an evaluation by a health care provider if is suspected ADHD and may include:

– Questionnaires for parents and teachers (for example, Connors, Burks)

– Psychological Evaluation of the child and family, including an examination of IQ and psychological tests

– Evaluation mental, nutritional, physical, psychosocial, and complete development

In older children, ADHD is in partial remission when they still have symptoms but no longer meet the full definition of the disorder.

Until today, they had not laboratory tests that were established as diagnostic tests in the clinical evaluation for attention deficit hyperactivity disorder, however, according to the findings of DR Healthcare there are, as described further.

Depression, lack of sleep, learning difficulties, the tic disorders, and behavior problems may be confused with, or appear along with the ADHD. When it is suspected that a child has this disorder, should be carefully examined by a specialist to rule out other possible conditions or reasons for this behavior.

Background in its treatment

The symptoms of ADHD express a biological problem and until now have been addressed through pharmacological treatment, which still constitutes the most important pillar of the therapeutic for many specialists, when in fact only aggravate the problem.

The usual treatments are based paradoxically in stimulants, which notes that modify positively the symptoms. Among them are amphetamine, caffeine and nicotine, with sometimes- medicate adolescents and adults. The first report suitable for endorsing the use of psychostimulants, dating back to the year 1937, when Charles Bradley established the effectiveness and apparent safety of amphetamine sulphate for the treatment of hyperactive children.

Currently, the most commonly used substances in the United States are methylphenidate (active principle behind the trade name Ritalin) and the d, l-amphetamine, followed by dexamphetamine and methamphetamine. Other psychostimulants, second-line drugs in the treatment of ADHD, are pemoline and modafinil.

In recent years the drugs of immediate effect tend to be replaced by other 50 preparations which, with the same active principles, achieve a more prolonged effect. The use of many of these drugs has been and are questioned by the side effects that are presented.

Although stimulants are the first line in the therapy of this disorder, some antidepressants such as fluoxetine, bupropion, venlafaxine, and desipramine, have shown some utility, particularly when the ADHD attends with comorbidities such as major depressive disorder or anxiety disorders (e.g., generalized anxiety disorder).

As has happened with other psychopathologies whose treatment is pre-eminently pharmacological therapy, both the diagnostic entity of ADHD as the viability of the medical treatment, have been openly rejected by 10 in favor of the so-called Antipsychiatry movements.

It is also accepted the psychological treatment of behavioral problems associated with it. This type of interventions is complementary to pharmacological treatment and usually seeks a reduction of disruptive behaviors of the child in different environments through framed therapies in normal cognitive-behavioral interventions.

It may also be advisable a psychopedagogical intervention on learning problems that usually appear in a large part of the subjects with ADHD. Therapies are currently being developed for positive development in children, who are trying to strengthen the potential aspects of young people through sport and group dynamics. Different researchers have developed models of reinforcement through economy of chips with groups of children with ADHD and it has been established that well-led gives better results than individual therapy. In this way can be explored aspects as self-esteem and social skills.

Research and proposal of DR Healthcare in the treatment and diagnosis of ADHD caused by DAO deficiency

The role of histamine in the etiology of ADHD

The histamine [2-(4-imidazolil)-ethylamine] is an important mediator of many biological processes including inflammation, the secretion of gastric acid, neuromodulation and regulation of immune function.

Due to its potent pharmacological activity, even at very low concentrations, it is necessary to regulate carefully in the synthesis, transport, storage, release and degradation of histamine in order to avoid undesirable reactions. It has been reported that high concentrations of histamine in circulation trigger unwanted effects, such as headaches, migraine headaches, stuffy or runny nose, obstruction of the airways, tachycardia, gastric and intestinal ailments own irritable bowel syndrome, muscle pain or fibromyalgia, erythema of the skin, decrease blood pressure or bronchospasm.

Histamine is produced by human beings themselves and is stored in an inactive form in the methacromatic granules of mast cells and basophils, leukocytes where it is available for immediate release. After the liberation, the histamine in an extraordinarily powerful mediator of a plurality of physiological and pathophysiological processes, often also through interaction with cytokines.

Histamine can also enter the human body from the outside, as it is generated by microbial action in the course of the food processing and, therefore, it is present in substantial quantities in many foods and fermented beverages.

Enzyme diamine oxidase (DAO): A New Biomarker for ADHD and main route of metabolism of exogenous histamine

The main route of inactivation of swallowed histamine is the  oxidative deamination of the primary amino group, catalyzed by the diamine oxidase (DAO) to give imidazolacetaldehide. The main function of the DAO is to prevent that ingested histamine reaches the blood circulation from the intestine.

In addition to the histamine, DAO can degrade other biogenic amines, such as putrescine, spermidine and cadaverine.

DAO has a molecular weight of approximately 182 kDa and a proportion of carbohydrates of 11%. Belongs to the class of the amine oxidases containing copper and that catalyze the oxidative deamination of primary amines to give aldehydes, ammonia and hydrogen peroxide. The DAO uses molecular oxygen for desaminate histamine to imidazolacetaldehide, ammonia and hydrogen peroxide by oxidation.

In addition to the inhibition of the DAO by certain types of substances, there is a significant percentage of the population whose levels of DAO in blood are abnormally low, which implies that the level of histamine in the blood is higher than the values considered normal (2-20 micrograms/0.1 L). In this type of subjects are triggered a whole series of pathologies caused by these high levels of histamine in the blood.

Clinical evidence of ADHD associated to DAO deficiency: DAO treatment and DAO activity

DR Healthcare has found that approximately 80% of children with ADHD also have a shortfall congenital defect of DAO activity, so that metabolize insufficiently histamine swallowed, turning it to the blood. The problem is compounded by the fact that most drugs that are prescribed in the treatment of ADHD are inhibitors of the activity of the DAO, entering into a pernicious loop. In the beginning these drugs palian symptoms, but in the long run they turn into chronic the symptoms and create a dependency and the need for dose increase, since more medication more inhibition of DAO and more step of histamine into the bloodstream.

The determination of DAO activity therefore represents a new and important biomarker for the objective diagnosis of ADHD, both from a genetic study of the genotypes implied and from a measurement of DAO plasmatic activity or a combination of both.

The administration of DAO supplementation in children and adults with ADHD diagnosed and with a DAO deficiency, it has been found that produce a significant improvement in symptoms and disorders that characterize the attention deficit hyperactivity disorder, also allowing the elimination of pharmacological treatment and its adverse effects.

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