Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.6 Attention Deficit/Hyperactivity Disorder

reveal an increased concordance in monozygotic compared to dizygotic twins, as well as a marked increased risk of 2 to 8 times for siblings as well as parents of an ADHD child, com- pared to the general population. Clinically, one sibling may have predominantly impulsivity/hyperactivity symptoms and others may have predominantly inattention symptoms. Up to 70 percent of children with ADHD meet criteria for a comor- bid psychiatric disorder, including learning disorders, anxiety disorders, mood disorder conduct disorders, and substance use disorders. Several hypotheses of the mode of transmission of ADHD have been proposed, including a sex-linked hypoth- esis, which would explain the significantly increased rates of ADHD in males. Other theories have focused on a model of interaction of multiple genes that produces the various symp- toms of ADHD. Numerous investigations continue to identify specific genes involved in ADHD. Cook and colleagues have found an association of the dopamine transporter gene (DAT1) with ADHD, although data from other research groups have not confirmed that result. Family studies and population-based stud- ies have found an association between the dopamine 4 receptor seven-repeat allele gene (DRD4) gene and ADHD. Most molec- ular research on ADHD has focused on genes that influence the metabolism or action of dopamine. Continued investigation is necessary to clarify the complex relationships between multiple interactive genes and the emergence of ADHD. Neurochemical Factors.  Many neurotransmitters are postulated to be associated with ADHD symptoms; however, dopamine is a major focus of clinical investigation, and the pre- frontal cortex has been implicated based on its role in attention and regulation of impulse control. Animal studies have shown that other brain regions such as locus ceruleus, which consists predominantly of noradrenergic neurons, also play a major role in attention. The noradrenergic system includes the central sys- tem (originating in the locus ceruleus) and the peripheral sym- pathetic system. Dysfunction in peripheral epinephrine, which causes the hormone to accumulate peripherally, may potentially feed back to the central system and “reset” the locus ceruleus to a lower level. In part, hypotheses regarding the neurochemistry of ADHD have arisen from the predictable effect of medica- tions. Simulants, known to be the most effective medications in the treatment of ADHD, affect both dopamine and norepineph- rine, leading to neurotransmitter hypotheses that may include dysfunction in both the adrenergic and dopaminergic systems. Stimulants increase catecholamine concentrations by promoting their release and blocking their uptake. Neurophysiological Factors.  EEG studies in ADHD chil- dren and adolescents over the last several decades have found evidence of increased theta activity, especially in the frontal regions. Further studies of youth with ADHD have provided data showing elevated beta activity in their electroencephalography (EEG) studies. Clarke and colleagues, studying EEG findings in children and adolescents over the last two decades found that those ADHD children with combined type of ADHD were the ones who showed significantly elevated beta activity on EEG, and further studies indicate that these youth also tend to show increased mood lability and temper tantrums. Current investi- gation of EEG in youth with ADHD have identified behavioral symptom clusters among children with similar EEG profiles.

ADHD has historically been described in the literature using different terminology. In the early 1900s, impulsive, disinhib- ited, and hyperactive children—many of whom also had neu- rological damage due to encephalitis—were grouped under the label hyperactive syndrome. In the 1960s, a heterogeneous group of children with poor coordination, learning disabilities, and emotional lability, but without specific neurological disor- ders, were described as having “minimal brain damage”; how- ever, over time, it became clear that this was an inappropriate term. Many hypotheses have been suggested to explain ADHD symptoms including theories of abnormal arousal and poor abil- ity to modulate emotions. This theory was initially supported by the observation that stimulant medications increased sus- tained attention and improved focus. ADHD is one of the most well-researched childhood psychiatric disorders with strong evidence-based treatments. Epidemiology Rates of ADHD have been reported to be 7 to 8 percent in pre- pubertal elementary school children. Epidemiologic studies suggest that ADHD occurs in about 5 percent of youth including children and adolescents, and about 2.5 percent of adults. The rate of ADHD in parents and siblings of children with ADHD is 2 to 8 times greater than in the general population. ADHD is more prevalent in boys than in girls, with the ratio ranging from 2:1 to as high as 9:1. First-degree biological relatives (e.g., siblings of probands with ADHD) are at high risk for devel- oping ADHD as well as other psychiatric disorders, including disruptive behavior disorders, anxiety disorders, and depressive disorders. Siblings of children with ADHD are also at higher risk than the general population for learning disorders and aca- demic difficulties. The parents of children with ADHD show an increased incidence of substance use disorders. Symptoms of ADHD are often present by age 3 years, but unless they are very severe, the diagnosis is frequently not made until the child is in kindergarten, or elementary school, when teacher information is available comparing the index child peers of the same age. Etiology Data suggest that the etiology ofADHD is largely genetic, with a heritability of approximately 75 percent. ADHD symptoms are the product of complex interactions of neuroanatomical and neurochemical systems evidenced by data from twin and adop- tion family genetic studies, dopamine transport gene studies, neuroimaging studies, and neurotransmitter data. Most children with ADHD have no evidence of gross structural damage in the central nervous system (CNS). In some cases, contributory fac- tors for ADHD may include prenatal toxic exposures, prematu- rity, and prenatal mechanical insult to the fetal nervous system. Food additives, colorings, preservatives, and sugar have been proposed as possible contributing causes of hyperactive behav- ior; however, studies have not confirmed these theories. Nei- ther artificial food coloring nor sugar have been established as causes of ADHD. There is no clear evidence that omega-3 fatty acids are beneficial in the treatment of ADHD. Genetic Factors.  Evidence for a significant genetic con- tribution to ADHD has emerged from family studies, which