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Attention deficit/hyperactivity disorder (ADHD)

Symptoms of inattention, impulsiveness and hyperactivity.

A childhood-onset neurodevelopmental disorder characterized by developmentally inappropriate and impaired attention, hyperactivity, and impulsivity, with is difficulties often continuing into adulthood.

ADHD suggest that it is associated with functional impairments in some of the brain’s neurotransmitter systems, and nvolve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex.

Causes excessive activity, concentration problems and difficulty controlling impulses.

There are three types of ADHD: the predominantly inattentive type, the predominately hyperactive/impulsive type, and the combined type.

Diagnosis requires the presence of symptoms across more than one setting, such as home and school, and requires that symptoms needed for diagnosis result in impairment in academic, social, or occupational functioning.

The disorder is commonly diagnosed in children, and up to 70% of childhood cases, and the symptoms that lead to impaired functioning persist into adulthood.

Onset is early, before age 12.

No evidence of increasing incidence.

Over the past two decades rates of diagnosis and treatment has increased.

Among children 2-5 years of age the rate of diagnose increased by more than 50% from 2007-2012.

The percentage of preschool aged children in the US diagnosed with ADHD is estimated to be 2.4% in 2016 and has been increasing over the past decade.
Pre-school aged children with ADHD or risk for expulsion from preschool and future academic underachievement.
Treatment is recommended for initial ADHD intervention for young children with consideration of methylphenidate treatment when behavior treatment is insufficient.
Preschool ADHD treatment for children age 3-5.5 years revealed that methylphenidate significantly reduced ADHD symptoms, however more than 40% of children had irritability, more than 20% had crying or were tearful/sad/depressed.

In 2016 5.2% of all children 2-17 years of age in United States were taking medication to treat ADHD.

In a meta-analysis of published studies the rate may be increasing in some populations , with an estimated involvement of 7% of youth.

Male: female ratio 3-4:1.

Frequent distractibility, inability to sustain attention to tasks, goals, and to others.

Unable to control impulsive decisions and behaviors.

Patients have marked heterogeneity on clinical, etiological, and pathophysiological basis.

No single risk factor is necessary or sufficient to explain ADHD and mainly genetic and non genetic factors contribute to risk.

Most cases are multifactorial in origin, but there are several known rare genetic syndromes such as fragile X syndrome, tuberous sclerosis, 22q11 microdeletion, and Williams syndrome, characterized by high rates of ADHD and ADHD-like features.

The pattern of inheritance is multi factorial for most patients.

Is a familial disorder with a relative risk of about 5-9 in first-degree relatives of

probands with ADHD.

Approximately 4.4% of adults in the United States have this process ( Kessler RC et al).

ADHD is diagnosed in 3% to 5% of the US population.

Twin studies show very high heritability estimates of about 76%, a magnitude similar to schizophrenia and autism.

Diagnosis based on the child’s behavior, as observed by teachers or parents, relative to the behavior of other children in the same school grade.

Characterized by impaired  attention span, hyperactivity, and impulsivity.

Core features of the disease tend to decline with age, although inattentiveness is it likely to persist.

Adult patients frequently cannot or will not take medications and many have poor therapeutic response to such agents ( Prince J  et al.).

Heterogeneous presentation and clinical factors are highly variable.

65% of patients continue to meet full criteria or have partial remission by adulthood, some patients achieve full remission.

Adult patients may only respond partially to drugs and may continue to experience significant symptoms.

Adult prevalence of approximately 2 1/2%

Associated with excessive talking, frequent interruption of others, unable to delay gratification, inability to wait for things, more prone to risk taking.

Shows a high concurrent comorbidities with other neurodevelopmental disorders autism spectrum disorder, communication and specific learning or motor disorders, intellectual disability and tic disorders.

High concurrent comorbidity with behavioral problems namely, defiance and conduct disorders.

Conduct disorder is a marker for greater neurocognitive impairment and worse prognosis in

children with ADHD.

Many have difficulty controlling activity levels.

Typically fidgety, restless, irrelevant behavior, hyperactive and have behavior that is inappropriate to the situation.

Impairs school and work performance.

Interferes with personal relationships.

Reduces chance of success in many aspects of life.

Increased the risk of tobacco use, injuries, motor vehicle accidents and substance abuse.

More frequent use of digital media may be associated with the development of ADHD symptoms.

Hyperactivity more likely to be present in childhood, and decreases by adolescence and adulthood, with replacement with restlessness and need to be busy.

More than 60% have symptoms into adolescence and adulthood.

Most commonly diagnosed in children between ages of 6 and 12 years.

One of the most common neurodevelopmental disorders of childhood with an

estimated prevalence between 8-16% in school age children.

Approximately 4-8% of children are diagnosed with ADHD.

Hyperactivity more likely to be present in childhood, and decreases by adolescence and adulthood, with replacement with restlessness and need to be busy.

Prevalence does not vary by geographical location.

Approximately 10-35% of patients have immediate family members with ADHD.

30% of siblings of patients with ADHD also have the disorder.

Children with clinically diagnosed disease are heavier than the average child.

Overweight children are twice as likely to exhibit elevated rates of ADHD symptoms as

do their average weight counterparts.

Association of ADHD and obesity include: the presence of shared neurobiologic dysfunction involving dopaminer gif system and behavioral impact of impulsivity and inattention in

ADHD contributing to weight gain via dysregulated eating patterns.

Prenatal and perinatal factors associated with ADHD are low birth weight, prematurity, in utero exposure to maternal stress, cigarette smoking, alcohol, prescribed drugs and illicit substances.

Environmental toxins in utero or early childhood such as lead, pesticides, polychlorinated biphenyls are risk factors for ADHD.

Parents of patients with ADHD are at high risk of having the process.

The risk for comorbidity with other disorders is high.

A comorbid diagnosis of ADHD and depression occurs in approximately 20% to 30% of patients.

ADHD and anxiety occur together in over 25% of patients.o

These comorbidity rates are equally or more prevalent in adults as they are in children.

Approximately 20% of adults with Bipolar disorder also have ADHD.

Patients with bipolar disease and ADHD have lower rates of mania, greater impairments, lower remission rates, greater use of substance abuse, and more familial maladjustment than the bipolar disease alone adults.

Associated with abnormalities in the frontal lobes.

May be associated with functional impairments in some of the brain’s neurotransmitter systems, involving impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the locus coeruleus and prefrontal cortex.

In children with frontal lobe epilepsy almost 90% with abnormal electroencephalography (EEG) readings had a concurrent of ADHD, compared with only 25% of children with normal EEG readings.

Frontal lobe epilepsy is strongly linked to ADHD,

Divided into three types in the Diagnostic and Statistical Manual for Mental disorders DSM-IV.

Combined Type is the most common type accounting for 65% of cases and involves all characteristic findings.

The Predominantly Hyperactive Type lacks sufficient problems with inattentiveness to be diagnosed as the Combined Type, manifests with impulsive and hyperactive behavior.

Predominantly Hyperactive Type felt to be an early stage of Combined Type disease, as up to 90% will develop sufficient problems with attention and distractibility to be diagnosed later.

Remaining cases are diagnosed with a mild type of Combined Type disease.

Predominantly Inattentitive Type of disease have attention problems but do not have excessive activity levels or poor impulse control.

Genetic studies have identified gene polymorphisms associated with this process and include two dopamine genes (DRD4 and DAT 1 genes).

Brain dopamine neuro-transmissionis disrupted in this process and may be related to symptoms of inattention and impulsivity.

Maternal smoking and lead levels may affect the dopamine system of the brain.

Patients have reward and motivation deficits and children with this problem do not modify their behavior in the face of changing reward conditions.

The mesoaccumbens dopamine pathway, which projects from the ventral segmental area in the mid brain to the nucleus accumbens is critically involved in reward and motivation, and may be responsible for such deficits in ADHD (Johansen EB).

Up to 80%-85% of properly diagnosed children have improved symptoms with stimulant medications.

Children with ADHD who use stimulant medications generally have better relationships with others, perform better in school, are less distracted and less impulsive, with longer attention spans.

While amphetamines improve short-term symptoms, they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.

Medications are prescribed for more than 2.7 million children with ADHD and use of such drugs is associated with an increaed risk of serious cardiovascular events, but the magnitude is small with 3.1 serious cardiovascular events per 100,000 person years reported in children and young adults.

Attention-deficit/hyperactivity disorder (ADHD), is associated with functional, and structural brain changes.

Compared to healthy controls, adolescents with ADHD have lower gray matter volume in the caudate nucleus and poorer working memory function, and thinner medial temporal cortex bilaterally.

Cortex thickness is associated with hyperactivity symptoms.

Therapeutic doses of stimulants diminish the differences in brain structure between patients with ADHD and healthy persons.

The authors speculate that this normalization of brain structure is a possible basis for the clinical effects of ADHD medications.

In humans with ADHD, amphetamines, at therapeutic dosages, appear to improve brain development and nerve growth: 

 

 

Brain MRI studies suggest that long-term treatment with amphetamines decreases abnormalities in brain structure and function with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

 

Amphetamines improve function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

Long-term continuous stimulant therapy for ADHD reduces the  symptoms of ADHD, enhances  quality of life, academic achievement, functional outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, and social function.

 

Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.

 

Treatment for people with ADHD can be pharmacologic, nonpharmacologic, or both.

 

The average duration of treatment with stimulant drugs was 136 days and children and 230 days in adults. 

 

The highest rates of discontinuation of medication are reported in the patients 15-21 years of age. 

 

Reasons for discontinuation of medication include: side effects, perceived lack of effectiveness, dislike of taking medications, associated stigma issues and issues with transition from child to adult services.

A metanalysis showed it with an average duration of seven weeks with medications approved for ADHD there is superiority to placebo in decreasing the severity of inattention, hyperactivity, and impulsivity, with the largest effects found by amphetamines followed by methylphenidate.

The effects of methylphenidate in ADHD are not always positive as an increase of dopamine transporter availability in the brain of such patients may decrease treatment efficacy and exacerbate symptoms when the medication is not used.

Methylphenidate may affect brain restructuring and be altered by the age of the patient indicating methylphenidate affects adult and adolescent brains differently.

Methylphenidate and amphetamines can lead to psychosis during such stimulant therapy: incidence is higher with amphetamines.

Non-stimulants including atomoxetine, extended release clonidine, and guanfacine are additional agents.

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