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ScienceWeek
MEDICAL BIOLOGY: ON ATTENTION DEFICIT-HYPERACTIVITY DISORDER
The following points are made by Marsha D. Rappley (New Engl. J. Med. 2005 352:165):
1) Consider the following: A mother brings in her eight-year-old son for evaluation after he is suspended from riding the school bus for jumping out of his seat, teasing other children, and not following directions. He spends two to three hours a night with homework that he never successfully completes. Does the child have attention deficit-hyperactivity disorder?
2) Attention deficit-hyperactivity disorder (ADHD) is characterized by the inability to marshal and sustain attention, inability to modulate activity level, and inability to moderate impulsive actions. The result is maladaptive behaviors that are inconsistent with age and developmental level.
3) Evidence from neuropsychological, pharmacologic, and brain-imaging studies implicates dopamine and norepinephrine neurotransmitter systems in frontostriatal circuitry in the pathophysiology of the disorder. Genetic factors appear to play an important role.[1,2,3] Extremely low birth weight (less than 1000 g)[4] and environmental conditions, such as head trauma and exposure to lead, are also associated with symptoms of ADHD.
4) The diagnosis of ADHD requires the identification of specific behaviors that meet the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised (DSM-IV-R)[5]. Three types of ADHD are diagnosed: combined inattentive, hyperactive, and impulsive (about 80 percent of patients); predominantly inattentive (about 10 to 15 percent); and predominantly hyperactive and impulsive (about 5 percent).
5) The prevalence of ADHD is estimated at 3 to 7 percent of all children. Boys are more often affected than girls (the ratio ranges, according to the population studied, from 9 to 1 to 2.5 to 1), but increasingly, cases involving girls are being identified.[5] ADHD is a chronic condition with symptoms experienced over a lifetime.
6) The subjective nature of judging behavior contributes to concern that ADHD is overdiagnosed and overtreated. Epidemiologic studies consistently show either underdiagnosis or overdiagnosis, with wide geographic and demographic variation. Data are not yet available to assess the long-term benefits and risks of medication. Although a concern has been raised regarding a risk of substance abuse in patients treated with stimulant medication, studies indicate that children with ADHD who are treated have a lower risk of substance abuse later in life than children with ADHD who are not treated.
References (abridged):
1. Nigg JT, Quamma JP, Greenberg MT, Kusche CA. A two-year longitudinal study of neuropsychological and cognitive performance in relation to behavioral problems and competencies in elementary school children. J Abnorm Child Psychol 1999;27:51-63
2. Durston S. A review of the biological bases of ADHD: what have we learned from imaging studies? Ment Retard Dev Disabil Res Rev 2003;9:184-195
3. Castellanos FX, Lee PP, Sharp W, et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 2002;288:1740-1748
4. Hille ET, den Ouden AL, Saigal S, et al. Behavioural problems in children who weigh 1000 g or less at birth in four countries. Lancet 2001;357:1641-1643
5) Diagnostic and statistical manual of mental disorders, 4th ed. rev.: DSM-IV-R. Washington, D.C. American Psychiatric Association, 2000
New Engl. J. Med. http://www.nejm.org
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MEDICAL BIOLOGY: ON ATTENTION-DEFICIT/HYPERACTIVITY IN ADULTS
The following points are made by T.E. Wilens et al (J. Am. Med. Assoc. 2004 292:619):
1) Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder estimated to affect 3% to 9% of school-aged children and approximately 4% of adults worldwide.(1-3) Although in the past it was thought that ADHD did not continue beyond adolescence, long-term controlled follow-up studies have shown that the disorder persists in a sizable number of adults who had been diagnosed as having ADHD in childhood.(4)
2) Longitudinal studies in ADHD youth show that symptoms of hyperactivity and impulsivity may decay, but inattention tends to persist.(5) Studies of clinically referred adults with ADHD show that about half have clinically important levels of hyperactivity and impulsivity and up to 90% have prominent attentional symptoms. Like some youth with ADHD, adults with ADHD tend to have additional cognitive deficits, specifically executive function deficits, which include problems encoding and manipulating information and difficulties with organization and time management.
3) Adults with ADHD typically have childhood histories reflecting school dysfunction, including deficits in educational performance, discipline problems, and high rates of repeated grades, tutoring, placement in special classes, and reading disabilities. School problems faced by children with ADHD often continue or worsen in college, resulting in academic underachievement, low grade point averages, lower completion rates, and more time to complete degrees.(2) Adults with ADHD tend to have lower socioeconomic status, lower rates of professional employment, more frequent job changes, more work difficulties, and high rates of spousal separation and divorce. Similarly, adults with ADHD have more speeding violations, driver's license suspensions, and automobile collisions, and they perform poorly in driving simulators.(3) Adults with addictions (eg, alcohol or other drug abuse, tobacco, gambling), repeated traffic violations (speeding, failure to renew license), and recurrent life failures (occupational, financial, academic)--especially in the context of a family history of ADHD -- should be screened for ADHD.
4) Family, twin, adoption, and molecular genetic studies show that genes influence the etiology of ADHD. The heritability of the disorder, about 70%, is among the highest for psychiatric disorders. Family studies show that ADHD is more prevalent among the relatives of children with ADHD, and the biological children of adults with ADHD are at high risk of having ADHD themselves. This high familial loading of adult ADHD suggests that biological factors may be stronger in adults than in pediatric ADHD.
5) Studies of children and adults have found evidence for the involvement of several genes in the etiology of ADHD: the D2 dopamine-receptor gene, the dopamine-beta-hydroxylase gene, the dopamine transporter gene, the SNAP 25, and the D4 dopamine-receptor gene, and others. The data for the D4 receptor are especially compelling because the gene variant associated with ADHD is known to mediate a blunted response to the neurotransmitters norepinephrine and dopamine, important neurotransmitters associated with the pathophysiology of ADHD.
6) A substantial body of literature implicates abnormalities of brain structure and function in the pathophysiology of both childhood and adult ADHD. We have known for decades that ADHD youth show impaired performance on tasks requiring vigilance, motoric inhibition, organization, planning, complex problem-solving ability, verbal learning, and memory. A recent meta-analysis has demonstrated that a smaller but substantial literature shows similar problems in adults with ADHD. Age, learning disabilities, psychiatric comorbidity, and gender do not account for these impairments.
References (abridged):
1. Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition? W Psychiatry. 2003;2:104-113
2. Heiligenstein E, Conyers LM, Berns AR, Miller MA, Smith MA. Preliminary normative data on DSM-IV attention deficit hyperactivity disorder in college students [published correction appears in J Am Coll Health. 1998;46:213]. J Am Coll Health. 1998;46:185-188
3. Murphy K, Barkley RA. Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers: implications for clinical diagnosis. J Attent Disord. 1996;1:147-161
4. Weiss G, Hechtman L, Milroy T, Perlman T. Psychiatric status of hyperactives as adults: a controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry. 1985;24:211-220
5. Achenbach TM, Howell C, McConaughy S, Stanger C. Six-year predictors of problems in a national sample, IV: young adult signs of disturbance. J Am Acad Child Adolesc Psychiatry. 1998;37:718-727
J. Am. Med. Assoc. http://www.jama.com
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MEDICINE: ADULT ATTENTION DEFICIT/HYPERACTIVITY DISORDER
The following points are made by Lynne Lamberg (J. Am. Med. Assoc. 2003 290:1565):
1) Although attention-deficit/hyperactivity disorder (ADHD) was long perceived as a disorder of children, it is now recognized as a chronic condition persisting into adulthood. But it is often undiagnosed in adults -- an unfortunate oversight, because appropriate treatment often can help those who have struggled with the effects of their condition for years. ADHD affects 3% to 7% of school-aged children, and it is now thought it affects approximately the same percentage of adults. But children and adults often manifest the disorder's core symptoms of hyperactivity, impulsivity, and inattention in different ways.
2) The hyperactive child squirms and fidgets, can't stay seated, and is constantly on the go. While hyperactivity lessens with age, adults with ADHD may experience subjective inner restlessness. Some become workaholics and have trouble relaxing. Impulsivity makes children with ADHD blurt out answers, interrupt others, and talk excessively. Adults with ADHD also are often incessant talkers, and may display impatience; studies reveal they change jobs more often, accrue more speeding tickets, and have more vehicle crashes than individuals without the disorder. As a group, adults with ADHD also have higher divorce rates and are more likely to smoke, have substance use disorders, and overeat more than other adults. Such behaviors often have serious medical consequences.
3) Inattention in children with ADHD is manifested by their propensity to not listen or follow through, as well as forgetfulness. Such tendencies have considerable impact as their lives unfold. Compared with peers of similar intelligence, for example, fewer enter college and fewer graduate. As inattentive adults, individuals with ADHD often find it hard to focus, plan, organize, and complete tasks at work and in their home lives. They generally advance more slowly at work than peers. Spouses complain that they neglect to pay bills or pick up the children at designated times, and misplace keys, glasses, and other items.
4) Some adults with ADHD harness their strengths, however, mobilizing intellectual curiosity, desire for novelty, and bountiful energy to achieve success as physicians, journalists, stockbrokers, lawyers, and sales people. Studies show that approximately one third of adults with ADHD become entrepreneurs by their 30s.
J. Am. Med. Assoc. http://www.jama.com
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ON BRAIN-VOLUME ABNORMALITIES IN CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
The following points are made by F.X. Castellanos et al (J. Am. Med. Assoc. 2002 288:1740):
1) Attention-deficit/hyperactivity disorder (ADHD), the most common childhood psychiatric disorder, is thought to reflect subtle abnormalities in central nervous system functioning.(1) For this reason, ADHD is being studied increasingly with a variety of brain imaging techniques throughout the life span. Magnetic resonance imaging (MRI) is particularly suitable for the study of pediatric patients, providing high-resolution images without ionizing radiation. Previous MRI neuroimaging studies, most with small samples, have reported smaller anatomic areas and/or volumes in patients with ADHD in regions of the corpus callosum,(2-5) smaller volumes and/or hypoactivation of prefrontal brain, basal ganglia, and cerebellum. However, a recent study noted inconsistencies in the ADHD neuroimaging literature and concluded that specific abnormalities have not yet been convincingly demonstrated.
2) The authors report a study to compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. The case-control study was conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. Using completely automated methods, the main outcome measures were initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls.
3) Results: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%) and in significantly smaller cerebellar volumes (-3.5%). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (-5.8%) and cerebellar volumes (-6.2%). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F2,288 = 11.65) compared with controls (-10.7%) and with medicated children with ADHD (-8.9%). Volumetric abnormalities persisted with age in total and regional cerebral measures (P = .002) and in the cerebellum (P = .003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P = .05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were < .05).
4) The authors conclude: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.
References (abridged):
1. Tannock R. Attention deficit hyperactivity disorder: advances in cognitive, neurobiological, and genetic research. J Child Psychol Psychiatry. 1998;39:65-99.
2. Hynd GW, Semrud-Clikeman M, Lorys AR, et al. Corpus callosum morphology in attention-deficit hyperactivity disorder: Morphometric analysis of MRI. J Learn Disabil. 1991;24:141-146.
3. Giedd JN, Castellanos FX, Casey BJ, et al. Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder. Am J Psychiatry. 1994;151:665-669.
4. Semrud-Clikeman M, Filipek PA, Biederman J, et al. Attention-deficit hyperactivity disorder: magnetic resonance imaging morphometric analysis of the corpus callosum. J Am Acad Child Adolesc Psychiatry. 1994;33:875-881.
5. Baumgardner TL, Singer HS, Denckla MB, et al. Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder. Neurology. 1996;47:477-482.
J. Am. Med. Assoc. http://www.jama.com
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