Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset

Zametkin, Alan J.; Nordahl, Thomas E.; Groß, Michael; King, Anna C.; Semple, William E.; Rumsey, Judith M.; Hamburger, Susan; Cohen, Robert M.

doi:10.1056/nejm199011153232001

Cited by 848 publications

(361 citation statements)

References 22 publications

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“…Studies on the SHR implicate dopaminergic and noradrenergic systems de Villiers et al 1995;Papa et al 1998;King et al 2000) but do not support a simple theory of altered dopamine neurotransmission in ADHD. Structural brain imaging studies have shown abnormalities in the frontal lobe and subcortical structures (globus pallidus, caudate, corpus callosum), regions known to be rich in dopamine neurotransmission and important in the control of attention and response to organization (Lou et al 1990;Zametkin et al 1990;Rubia et al 1997). The most consistent findings from functional neuroimaging studies in humans are hypoactivity of frontal cortex and subcortical structures, usually on the right side (Faraone and Biederman, in press).…”

Section: Evidence Supporting a Dopamine Hypothesis In Adhd And The Comentioning

confidence: 99%

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

106

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Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD).Attention Deficit Hyperactivity Disorder (ADHD) is a common condition of childhood affecting 3-6% of school age children worldwide (Barkley 1990), with males being affected three times more than females (Anderson et al. 1987; Baumgartel et al. 1995). Its core clinical features include excessive motor activity, impaired attention, and impulsivity. ADHD causes marked educational, social, and family difficulties for sufferers and their relatives. The condition is of early onset (usually before age 7) and tends to persist throughout childhood. Moreover, approximately 30-60% of children with ADHD have persisting psychopathology in adulthood (Gittelman et al. 1985;Weiss and Hechtman 1986; Barkley 1990;Swanson et al. 1998a). The exact etiology of ADHD is Received March 8, 2001; revised February 12, 2002; accepted February 20, 2002. Online publication: 2/28/02 at www.acnp.org/citations/ Npp022802254. 608 A. Kirley et al. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 4 unknown, but a substantial genetic element exists. This has been demonstrated by family (Biederman et al. 1990(Biederman et al. , 1992Faraone et al., 1992Faraone et al., , 1994, twin (Thapar et al. 1995;Silberg et al. 1996;Levy et al. 1997), and adoption studies (Alberts-Corush et al. 1986; Cadoret and Stewart 1991). The heritability (h 2 ) of ADHD has been estimated to be .50-.98 (Gjone et al. 1996;Levy et al. 1997). The exact mode of transmission remains unknown. Segregation analyses (Morrison and Steward 1974;Deutsch et al. 1990, Faraone et al. 1992, Hess et al. 1995 have proposed models of inheritance from major gene effects through oligogenic to polygenic and multifactorial models, but the differences in statistical "fit" between multifactorial genetic models and single gene inheritance is modest. The multifactorial concept is consistent with ADHD's high population prevalence (2-7%), high concordance in monozygotic twins (68-81%), but modest recurrence risks to first-degree relatives.Dysregulation in catecholamine neurotransmission is implicated in the pathophysiology of ADHD (Faraone and Biederman 2002). The dopaminergic neurotransmitter system has been most extensively studied. This article will focus mainly on its role in the etiology of ADHD. Evidence to support dopaminergic dysfunction in ADHD derives from three research areas: the neuropharmacology of stimulant medication (Zametkin and Rapoport 1987; Amara and Kuhar 1993), the behavior and biochemistry of animal models (Giros et al. 1996;Gainetdinov et al. 1999, Russell 2000, and neuroimaging studies in ADHD adults (Dougherty et al. 1999, Krause et al. 2000, and Faraone and Biederman 2002. For this reason, many molecular genetic studies have focused on dopamine system genes.The gene encoding the dopamine transporter, DAT1, was the initial candidate gene studied. This gene is of particular interest, as the transporter is the principal target...

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Section: Evidence Supporting a Dopamine Hypothesis In Adhd And The Comentioning

confidence: 99%

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

106

View full text Add to dashboard Cite

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“…The frontal cortex is also implicated as a substrate for ADHD and MPH with accumulating evidence pointing to abnormalities in structural volume (Castellanos et al, 1996) and function (Bush et al, 1999;Rubia et al, 1999;Schweitzer et al, 2000;Vaidya et al, 1998;Zametkin et al, 1990) in this region in subjects with ADHD. Early PET-imaging studies on stimulant administration (acute oral, chronic oral, and intravenous administration) showed a lack of effect on frontal glucose metabolism in adults with ADHD (Ernst et al, 1994(Ernst et al, , 1997Matochik et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

A Positron Emission Tomography Study Of Methylphenidate in Adults with ADHD: Alterations in Resting Blood Flow and Predicting Treatment Response

Schweitzer

Lee

Hanford

et al. 2002

Neuropsychopharmacol

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A hallmark symptom of attention-deficit hyperactivity disorder (ADHD) is an excess of motoric behavior or hyperactivity. Methylphenidate (MPH) is known to reduce hyperactivity in individuals with ADHD. Yet little is known about how it alters neural activity and how this relates to its clinical effects. The goal of this study is to examine MPH-induced changes during resting brain metabolism, and to examine how these changes correlate with measures of behavioral response to the drug. Measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) were acquired at rest for ten adult subjects with ADHD during both an unmedicated state and after a 3-week period of chronic dosing with a clinically optimal dose of MPH. Compared with the on-MPH condition, the off-MPH condition was associated with relative increases in rCBF bilaterally in the precentral gyri, left caudate nucleus, and right claustrum. The on-MPH condition was associated with relative increases in rCBF in the cerebellar vermis. A correlational analysis measured the relation between rCBF in the off-medication condition to change in ADHD ratings between the off-and on-MPH condition to identify brain regions associated with treatment response. The degree of change in the ratings was negatively correlated with rCBF increases in the midbrain, cerebellar vermis, and the precentral and middle frontal gyri in the off-MPH condition. The majority of these brain regions are involved in the planning and execution of motor behavior. These data suggest that MPH modulates brain regions associated with motor function to achieve a reduction in ADHD symptoms.

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“…In each instance, however, the direction of these changes (vs. regional control values) is different than that which we observed in TS patients. Obsessive compulsive disorder appears to be associated with in creased metabolic rates in the orbitofrontal cortices and basal ganglia (Baxter et al 1987;Nordahl et al 1989;Swedo et al 1989), and ADHD is associated with decreases in superior sensorimotor structures, centered in the premotor cortices (Zametkin et al 1990) .…”

Section: Relationship To Other Functional Neuroimaging Studiesmentioning

confidence: 99%

The Functional Neuroanatomy of Tourette's Syndrome: An FDG-PET Study. I. Regional Changes in Cerebral Glucose Metabolism Differentiating Patients and Controls

Braun

Stoetter

Randolph

et al. 1993

Neuropsychopharmacol

158

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Regional metabolic rates for glucose estimated using [18Flfluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age-and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbenslventromedial caudate) and in the midbrain. Published by Elsevier Science Publishing Co., Inc.655 Avenue of the Americas, New York, NY 10010These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

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Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset

Abstract: Glucose metabolism, both global and regional, was reduced in adults who had been hyperactive since childhood. The largest reductions were in the premotor cortex and the superior prefrontal cortex--areas earlier shown to be involved in the control of attention and motor activity.

Cited by 848 publications

References 22 publications

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

A Positron Emission Tomography Study Of Methylphenidate in Adults with ADHD: Alterations in Resting Blood Flow and Predicting Treatment Response

The Functional Neuroanatomy of Tourette's Syndrome: An FDG-PET Study. I. Regional Changes in Cerebral Glucose Metabolism Differentiating Patients and Controls

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