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3
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0030872119
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Hyperkinetic disorders and attention deficit hyperactivity disorders
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This paper presents a comparison of the DSM-IV criteria for ADHD and the ICD-9 criteria for HKD (which is still used for cross-referencing in the DSM-IV manual). of special interest
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Swanson JM. Hyperkinetic disorders and attention deficit hyperactivity disorders. Curr Opin Psychiatry. 10:1996;300-305 This paper presents a comparison of the DSM-IV criteria for ADHD and the ICD-9 criteria for HKD (which is still used for cross-referencing in the DSM-IV manual). of special interest.
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Curr Opin Psychiatry
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Swanson, J.M.1
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4
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0032492176
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This paper compares the DSM-IV criteria with the ICD-10 criteria, and proposes the use of their overlap (ADHD/HKD) as a refined phenotype. Cross-national differences in diagnosis, administrative prevalence, and treatment are discussed, and converging evidence about epidemiology and pathophysiology of ADHD/HKD is reviewed. of outstanding interest
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Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJS, Jensen PS, Cantwell DP. Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet. 351:1998;429-433 This paper compares the DSM-IV criteria with the ICD-10 criteria, and proposes the use of their overlap (ADHD/HKD) as a refined phenotype. Cross-national differences in diagnosis, administrative prevalence, and treatment are discussed, and converging evidence about epidemiology and pathophysiology of ADHD/HKD is reviewed. of outstanding interest.
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Swanson, J.M.1
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Jensen, P.S.5
Cantwell, D.P.6
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0030797044
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Comorbidity in ADHD: Implications for research, practice, and DSM-V
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Cantwell's eight domains (phenomenology, demographics, psychosocial factors, biological factors, genetic factors, family factors, natural history, and response to treatment) were used to evaluate the validity of comorbid disorders. The authors report support for comorbid ADHD plus conduct and anxiety disorders. of special interest
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Jensen PS, Martin D, Cantwell DP. Comorbidity in ADHD: implications for research, practice, and DSM-V. J Am Acad Child Adolesc Psychiatry. 36:1997;1065-1079 Cantwell's eight domains (phenomenology, demographics, psychosocial factors, biological factors, genetic factors, family factors, natural history, and response to treatment) were used to evaluate the validity of comorbid disorders. The authors report support for comorbid ADHD plus conduct and anxiety disorders. of special interest.
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J Am Acad Child Adolesc Psychiatry
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Jensen, P.S.1
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The natural history of untreated ADHD/HKD was clarified by this report of a 10-year follow-up study, which identified hyperactive behavior as a strong risk factor for later psychiatric diagnosis, antisocial behavior, and social and peer problems, even after allowing for the initial coexistence of conduct disorder. of outstanding interest
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Taylor E, Chadwick O, Heptinstall E, Danckaerts M. Hyperactivity and conduct problems as risk factors for adolescent development. J Am Acad Child Adolescent Psychiatry. 35:1996;1213-1216 The natural history of untreated ADHD/HKD was clarified by this report of a 10-year follow-up study, which identified hyperactive behavior as a strong risk factor for later psychiatric diagnosis, antisocial behavior, and social and peer problems, even after allowing for the initial coexistence of conduct disorder. of outstanding interest.
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Taylor, E.1
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Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD
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A theory of ADHD was proposed based on the central concept of 'behavioral inhibition', derived from the work of Bronowski and Fuster, which suggests that symptoms of hyperactivity - impulsivity are the primary symptoms of ADHD and that symptoms of inattention are secondary (i.e. the consequence of poor behavioral inhibition). of outstanding interest
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Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 121:1997;65-94 A theory of ADHD was proposed based on the central concept of 'behavioral inhibition', derived from the work of Bronowski and Fuster, which suggests that symptoms of hyperactivity - impulsivity are the primary symptoms of ADHD and that symptoms of inattention are secondary (i.e. the consequence of poor behavioral inhibition). of outstanding interest.
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Barkley, R.A.1
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H.C. Quay, Hogan A.E. Plenum Press, New York
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Sergeant JA, Oosterlaan J, Van der Meere J. Hyperactivity: passed the point of no return? A cognitive energetic analysis. Quay HC, Hogan AE. Handbook of Disruptive Behavior Disorders. 1998;Plenum Press, New York.
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Sergeant, J.A.1
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Parasuramann R. MIT press, Cambridge, Massachusetts
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Swanson JM, Posner M, Cantwell D, Wigal S, Crinella F, Filipek PA, Emerson J, Tucker D, Nalcioglu O. Attention-deficit/hyperactivity disorder: symptom domains, cognitive processes and neural networks. Parasuramann R. The Attentive Brain. 1998;445-460 MIT press, Cambridge, Massachusetts.
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Swanson, J.M.1
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Cantwell, D.3
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Nalcioglu, O.9
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10
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In this study of 51 ADHD subjects and 31 controls, tasks requiring rapid work were better for distinguishing the groups than tasks requiring deliberation and delayed responding. Within a set of rapid work tests, ADHD subjects responded slower than control subjects, and those tasks requiring controlled processing were better for distinguishing ADHD from control subjects than those requiring automatic processing. of outstanding interest
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Carte ET, Nigg JT, Hinshaw SP. Neuropsychological functioning, motor speed, and language processing in boys with and without ADHD. J Abnorm Child Psychol. 24:1996;481-498 In this study of 51 ADHD subjects and 31 controls, tasks requiring rapid work were better for distinguishing the groups than tasks requiring deliberation and delayed responding. Within a set of rapid work tests, ADHD subjects responded slower than control subjects, and those tasks requiring controlled processing were better for distinguishing ADHD from control subjects than those requiring automatic processing. of outstanding interest.
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J Abnorm Child Psychol
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Carte, E.T.1
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Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder
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This study evaluated the ability of ADHD and control children to inhibit attention to "salient but otherwise irrelevant stimuli" during three stages of information processing: sensory selection, response selection, and response execution. Regression analyses were used to relate performance measures on each task to size of frontal and striatal brain regions, and significant differences in the size/accuracy correlations slopes were reported for the ADHD and control group, implicating right prefrontal, right caudate, and left globus pallidus. of outstanding interest
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Casey BJ, Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Schubert AB, Vauss YC, Vaituzis AC, Dickstein DP, Sarfatti SE, Rapoport JL. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 36:1997;374-383 This study evaluated the ability of ADHD and control children to inhibit attention to "salient but otherwise irrelevant stimuli" during three stages of information processing: sensory selection, response selection, and response execution. Regression analyses were used to relate performance measures on each task to size of frontal and striatal brain regions, and significant differences in the size/accuracy correlations slopes were reported for the ADHD and control group, implicating right prefrontal, right caudate, and left globus pallidus. of outstanding interest.
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J Am Acad Child Adolesc Psychiatry
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Casey, B.J.1
Castellanos, F.X.2
Giedd, J.N.3
Marsh, W.L.4
Hamburger, S.D.5
Schubert, A.B.6
Vauss, Y.C.7
Vaituzis, A.C.8
Dickstein, D.P.9
Sarfatti, S.E.10
Rapoport, J.L.11
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0029996407
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This review presented discussions of the 'frontal metaphor', a definition of executive functions, and measurement issues unique to developmental psychopathology. Meta analyses provided the empirical bases for identifying executive function deficits in specific disorders (ADHD and autism) but not others (conduct disorder without ADHD and Tourette syndrome). of special interest
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Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 37:1996;51-87 This review presented discussions of the 'frontal metaphor', a definition of executive functions, and measurement issues unique to developmental psychopathology. Meta analyses provided the empirical bases for identifying executive function deficits in specific disorders (ADHD and autism) but not others (conduct disorder without ADHD and Tourette syndrome). of special interest.
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Pennington, B.F.1
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Pennington BF, Bennetto L, McAleer O, Roberts RJ. Executive functions and working memory: theoretical and measurement issues. Lyon GR, Krasnegor NA. Attention, Memory, and Executive Function. 1996;327-348 Paul Brookes, York, Pennsylvania.
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Pennington, B.F.1
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G.R. Lyon, Krasnegor N.A. Paul Brookes, York, Pennsylvania
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Denckla MB. A theory and model of executive function: a neuropsychological perspective. Lyon GR, Krasnegor NA. Attention, Memory, and Executive Function. 1996;263-278 Paul Brookes, York, Pennsylvania.
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Denckla, M.B.1
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Posner MI, Digirolamo GJ. Conflict, target detection, and cognitive control. Parasuramann R. The Attentive Brain. 1998;401-423 MIT Press, Cambridge, Massachusetts.
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Posner, M.I.1
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Sophisticated segmentation and parcellation of MRI images were used to investigate hemispheric and structural volumes in 15 'pure' (non-comorbid) ADHD subjects and 15 control subjects. Analysis was performed to test specific predictions about anomalies based on the Posner and Raichle neuroanatomical network theory of attention and significant differences between ADHD children and controls were reported for caudate, anterior superior, and anterior inferior brain regions. of outstanding interest
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Filipek PA, Semrud-Clikeman M, Steingard RJ, Renshaw PF, Kennedy DN, Biederman J. Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology. 48:1997;589-601 Sophisticated segmentation and parcellation of MRI images were used to investigate hemispheric and structural volumes in 15 'pure' (non-comorbid) ADHD subjects and 15 control subjects. Analysis was performed to test specific predictions about anomalies based on the Posner and Raichle neuroanatomical network theory of attention and significant differences between ADHD children and controls were reported for caudate, anterior superior, and anterior inferior brain regions. of outstanding interest.
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Filipek, P.A.1
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In this study of brain anatomy of 57 ADHD and 55 control children, the size and symmetry of 12 subcortical and cortical brain regions were measured. Significant differences between ADHD children and controls were observed for caudate and anterior frontal regions, providing support for the hypothesis of a deficit in right hemisphere frontal - striatal circuit as a pathophysiological basis for ADHD. of outstanding interest
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Castellanos FX, Giedd JN, March WL, Hamburger SD, Vaituzis AC, Dickstein DP, Sarfatti SE, Vauss YC, Snell JW, Lange N, et al. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 53:1996;607-616 In this study of brain anatomy of 57 ADHD and 55 control children, the size and symmetry of 12 subcortical and cortical brain regions were measured. Significant differences between ADHD children and controls were observed for caudate and anterior frontal regions, providing support for the hypothesis of a deficit in right hemisphere frontal - striatal circuit as a pathophysiological basis for ADHD. of outstanding interest.
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Arch Gen Psychiatry
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Castellanos, F.X.1
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This MRI study of 13 ADHD and an aged-matched control group revealed volumetric difference in caudate and globus pallidus, which is consistent with the findings for these brain regions in the study of larger groups by Castellanos et al. [18]. of outstanding interest of special interest
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Aylward EH, Reiss AL, Reader MJ, Singer HS, Brown JE, Denckla MB. Basal ganglia volumes in children with attention-deficit hyperactivity disorder. J Child Neurol. 11:1996;112-115 This MRI study of 13 ADHD and an aged-matched control group revealed volumetric difference in caudate and globus pallidus, which is consistent with the findings for these brain regions in the study of larger groups by Castellanos et al. [18]. of outstanding interest of special interest.
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Aylward, E.H.1
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Lou HC. Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr. 85:1996;1266-1271.
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A neurodevelopmental model was used to related dopamine levels to exploratory behavior and activity level. The dopamine input from two midbrain systems (from the ventral tegmental area and the substantia nigra) was emphasized in this detailed account of the operation of prefrontal-striatal-thalamic-cortical circuits. The complex working of the basal ganglia circuits was described, with an emphasis on the direct input to the cortex from dopamine cell bodies in the ventral tegmental area (which was linked to the symptoms of inattention) and the regulation of the striatal - thalamic input to the cortex by input from dopamine cell bodies in the substantia nigra (which was linked to the symptoms of hyperactivity-impulsivity). A dopamine deficit in the former and a dopamine excess in the latter system was suggested as a possible biochemical bases for ADHD/HKD. of outstanding interest
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Castellanos FX. Toward a pathophysiology of attention-deficit/hyperactivity disorder. Clin Pediatr. 36:1997;381-393 A neurodevelopmental model was used to related dopamine levels to exploratory behavior and activity level. The dopamine input from two midbrain systems (from the ventral tegmental area and the substantia nigra) was emphasized in this detailed account of the operation of prefrontal-striatal-thalamic-cortical circuits. The complex working of the basal ganglia circuits was described, with an emphasis on the direct input to the cortex from dopamine cell bodies in the ventral tegmental area (which was linked to the symptoms of inattention) and the regulation of the striatal - thalamic input to the cortex by input from dopamine cell bodies in the substantia nigra (which was linked to the symptoms of hyperactivity-impulsivity). A dopamine deficit in the former and a dopamine excess in the latter system was suggested as a possible biochemical bases for ADHD/HKD. of outstanding interest.
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Catecholamine theories of ADHD/HKD were evaluated. Based on the concepts of posterior and anterior attentional systems proposed by Posner and Petersen and elaborated by Posner and Raichle, likely neurochemical deficits associated with ADHD were proposed, based on neural circuits with subcortical norepinephrine inputs to the posterior attentional system (which operate to enhance the response to novel input) and neural circuits with subcortical dopamine input to the anterior attentional system (which operate to inhibit processing of new information and to prepare the individual for responding)., of special interest
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Pliszka SR, McCracken JT, Maas JW. Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J Am Acad Child Adolescent Psychiatry. 35:1996;264-272 Catecholamine theories of ADHD/HKD were evaluated. Based on the concepts of posterior and anterior attentional systems proposed by Posner and Petersen and elaborated by Posner and Raichle, likely neurochemical deficits associated with ADHD were proposed, based on neural circuits with subcortical norepinephrine inputs to the posterior attentional system (which operate to enhance the response to novel input) and neural circuits with subcortical dopamine input to the anterior attentional system (which operate to inhibit processing of new information and to prepare the individual for responding)., of special interest.
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A review of work with animals suggested that the effects of alpha2-noradrenergic drugs were to enhance working memory, and that this effect was mediated by postsynaptic alpha2a receptors in the prefrontal cortex, rather than through presynaptic inhibitory receptors. of special interest
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Arnsten AF, Steere JC, Hunt RD. The contribution of alpha2-noradrenergic mechanisms to prefrontal cortical cognitive function. Arch General Psychiatr. 53:1996;448-455 A review of work with animals suggested that the effects of alpha2-noradrenergic drugs were to enhance working memory, and that this effect was mediated by postsynaptic alpha2a receptors in the prefrontal cortex, rather than through presynaptic inhibitory receptors. of special interest.
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An antibody specific for the dopamine D4 receptor was produced for use in localizing the D4 receptor within specific cellular elements and brain circuits. D4 receptors were localized on GABAergic neurons in the cerebral cortex and hippocampus, in the reticular nucleus of the thalamus, in both segments of the globus pallidus but not the caudate or putamen, and pars reticulata of the substantia nigra. These are brain regions involved in cortical modulation by interneurons, thalamococortical activity, and basal ganglia loop circuits. The role of the D4 receptor in response to clozapine, an atypical anti-psychotic drug for the treatment of schizophrenia, is discussed. of outstanding interest
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0030941402
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11D]d-threo and I-threo-methylphenidate in the human and baboon brain
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C11-labeled D-methylphenidate and L-methylphenidate were used in a PET study to investigate pharmacokinetics in humans and baboons. After intravenous administration, nonspecific binding of the L-isomer and specific binding of the D-isomer to the dopamine transporter in basal ganglia was demonstrated. The methods for labeling the dopamine transporter [37] and mapping time-activity curves [38] were used to characterize the two optical isomers, D-threo-methylphenidate and L-threo-methylphenidate, which each make up 50% of the medication (Ritalin®) used in clinical treatment. Neuro-chemical specificity (high uptake in the basal ganglia) was demonstrated for the D-isomer, but uptake to the L-isomer was nonspecific (equal uptake in all brain regions). This study suggested that the pharmacological specificity of methylphenidate resides in the D-isomer. of outstanding interest
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11D]d-threo and I-threo-methylphenidate in the human and baboon brain. Psychopharmacology. 131:1997;71-78 C11-labeled D-methylphenidate and L-methylphenidate were used in a PET study to investigate pharmacokinetics in humans and baboons. After intravenous administration, nonspecific binding of the L-isomer and specific binding of the D-isomer to the dopamine transporter in basal ganglia was demonstrated. The methods for labeling the dopamine transporter [37] and mapping time-activity curves [38] were used to characterize the two optical isomers, D-threo-methylphenidate and L-threo-methylphenidate, which each make up 50% of the medication (Ritalin®) used in clinical treatment. Neuro-chemical specificity (high uptake in the basal ganglia) was demonstrated for the D-isomer, but uptake to the L-isomer was nonspecific (equal uptake in all brain regions). This study suggested that the pharmacological specificity of methylphenidate resides in the D-isomer. of outstanding interest.
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(1997)
Psychopharmacology
, vol.131
, pp. 71-78
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Ding, Y.S.1
Fowler, J.2
Volkow, N.3
Dewey, S.4
Wang, G.J.5
Logan, J.6
Gatley, S.J.7
Pappas, N.8
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40
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0030019923
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Cerebrospinal homovanillic acid predicts behavioral response to stimulants in 45 boys with attention-deficit/hyperactivity disorder
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In this study of 45 ADHD subjects, significant correlations (0.32 to 0.50) were reported between measures of response to stimulant medication and baseline HVA levels but not MHPG levels. This finding supports the hypothesis that response to stimulant medication is related to a measure of central dopamine activity (as subjects with low HVA levels tend to response less well to stimulant medication than subjects with high HVA levels). These finding are discussed with respect to three sites of action of dopamine: presynaptic compensation for postsynaptic deficits, overactive intraneuronal metabolism, and autoreceptor downregulation of excessive dopamine neurotransmission. of outstanding interest
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Castellanos FX, Elia J, Kruesi MJP, Marsh WL, Gulotta CS, Potter WZ, Ritchie GF, Hamburger SD, Rapoport JL, Kruesi MJ. Cerebrospinal homovanillic acid predicts behavioral response to stimulants in 45 boys with attention-deficit/hyperactivity disorder. Neuropsychopharmacology. 14:1996;125-137 In this study of 45 ADHD subjects, significant correlations (0.32 to 0.50) were reported between measures of response to stimulant medication and baseline HVA levels but not MHPG levels. This finding supports the hypothesis that response to stimulant medication is related to a measure of central dopamine activity (as subjects with low HVA levels tend to response less well to stimulant medication than subjects with high HVA levels). These finding are discussed with respect to three sites of action of dopamine: presynaptic compensation for postsynaptic deficits, overactive intraneuronal metabolism, and autoreceptor downregulation of excessive dopamine neurotransmission. of outstanding interest.
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(1996)
Neuropsychopharmacology
, vol.14
, pp. 125-137
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Castellanos, F.X.1
Elia, J.2
Kruesi, M.J.P.3
Marsh, W.L.4
Gulotta, C.S.5
Potter, W.Z.6
Ritchie, G.F.7
Hamburger, S.D.8
Rapoport, J.L.9
Kruesi, M.J.10
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41
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0032127304
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Neuropsychopharmacological mechanisms of stimulant drug action in attention deficit/hyperactivity disorder: A review and integration
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Solanto M. Neuropsychopharmacological mechanisms of stimulant drug action in attention deficit/hyperactivity disorder: a review and integration. Behavior Brain Res. 1998; On the basis of a review of a broad literature, the author proposes two main neuroanatomical loci for the effects of stimulant drugs: the nucleus accumbens (for reinforcement processes and motor activity) and locus coeruleus (for working memory). She interprets the effects as antagonistic, mediated by presynaptic inhibitory autoreceptors. of special interest.
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(1998)
Behavior Brain Res
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Solanto, M.1
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42
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0030071106
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Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
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Using in vivo homologous recombination, the authors created a strain of mice lacking the dopamine transporter (DAT). These mice displayed hyperactive behavior, as well as major adaptive changes (e.g. downregulation of mRNAs for D1 and D2 receptors). Clearance of dopamine from the synapse was increased from 1 s to 100 s, and administration of stimulants (cocaine or amphetamine) did not produce increased locomotor activity in these mutant mice. of outstanding interest
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Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature. 379:1996;606-612 Using in vivo homologous recombination, the authors created a strain of mice lacking the dopamine transporter (DAT). These mice displayed hyperactive behavior, as well as major adaptive changes (e.g. downregulation of mRNAs for D1 and D2 receptors). Clearance of dopamine from the synapse was increased from 1 s to 100 s, and administration of stimulants (cocaine or amphetamine) did not produce increased locomotor activity in these mutant mice. of outstanding interest.
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(1996)
Nature
, vol.379
, pp. 606-612
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Giros, B.1
Jaber, M.2
Jones, S.R.3
Wightman, R.M.4
Caron, M.G.5
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43
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0029165456
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Parkinsonian-like impairment in mice lacking dopamine D2 receptors
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Baik JH, Picetti R, Salardl A, Depaulla A, Le Meur M, Borrelil E. Parkinsonian-like impairment in mice lacking dopamine D2 receptors. Nature. 377:1995;424-428.
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(1995)
Nature
, vol.377
, pp. 424-428
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Baik, J.H.1
Picetti, R.2
Salardl, A.3
Depaulla, A.4
Le Meur, M.5
Borrelil, E.6
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44
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0027945523
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Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses
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Xu M, Moratalla R, Gold H, Hiroi N, Koob GF, Graybiel AM, Tonegawa S. Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell. 79:1994;729-742.
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(1994)
Cell
, vol.79
, pp. 729-742
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Xu, M.1
Moratalla, R.2
Gold, H.3
Hiroi, N.4
Koob, G.F.5
Graybiel, A.M.6
Tonegawa, S.7
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45
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0029877297
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A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice
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Targeted mutagenesis was used to obtain mice lacking functional D3 receptors. In homozygous mice, increased activity and exploratory behavior was observed. This may be interpreted to support the dopamine deficit hypothesis of ADHD. of special interest
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Accili D, Fishburn CS, Drago J, Steiner H, Lachowicz JE, Park BH, Guada EB, Lee EJ, Cool MH, Sibley DR, et al. A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Neurobiology. 93:1996;1945-1949 Targeted mutagenesis was used to obtain mice lacking functional D3 receptors. In homozygous mice, increased activity and exploratory behavior was observed. This may be interpreted to support the dopamine deficit hypothesis of ADHD. of special interest.
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(1996)
Neurobiology
, vol.93
, pp. 1945-1949
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Accili, D.1
Fishburn, C.S.2
Drago, J.3
Steiner, H.4
Lachowicz, J.E.5
Park, B.H.6
Guada, E.B.7
Lee, E.J.8
Cool, M.H.9
Sibley, D.R.10
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46
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0030955365
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Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine and methamphetamine
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Mutant mice that lacked the D4 receptor were produced by means of homologous recombination in embryonic stem cells. The mutant mice were less active (in novel and familiar environments) but more coordinated (as reflected by performance on the rotating rod test) than wild-type mice. They were supersensitive to cocaine, methamphetamine, and ethanol on locomotor tasks. In addition they were subsensitive to low doses of clozapine. However, the mutant mice also showed increased synthesis and turnover of dopamine in caudate and putamen. These results were discussed in terms of unbalanced dopamine signaling in the cortex and basal ganglia, altered motivational state due to an abnormality of the limbic system, and a shift in striatal transmission to the indirect pathway. of outstanding interest
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Rubenstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, et al. Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine and methamphetamine. Cell. 90:1996;991-1001 Mutant mice that lacked the D4 receptor were produced by means of homologous recombination in embryonic stem cells. The mutant mice were less active (in novel and familiar environments) but more coordinated (as reflected by performance on the rotating rod test) than wild-type mice. They were supersensitive to cocaine, methamphetamine, and ethanol on locomotor tasks. In addition they were subsensitive to low doses of clozapine. However, the mutant mice also showed increased synthesis and turnover of dopamine in caudate and putamen. These results were discussed in terms of unbalanced dopamine signaling in the cortex and basal ganglia, altered motivational state due to an abnormality of the limbic system, and a shift in striatal transmission to the indirect pathway. of outstanding interest.
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(1996)
Cell
, vol.90
, pp. 991-1001
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Rubenstein, M.1
Phillips, T.J.2
Bunzow, J.R.3
Falzone, T.L.4
Dziewczapolski, G.5
Zhang, G.6
Fang, Y.7
Larson, J.L.8
McDougall, J.A.9
Chester, J.A.10
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47
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0028987091
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Association of attention deficit disorder and the dopamine transporter gene
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Cook EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL. Association of attention deficit disorder and the dopamine transporter gene. Am J Hum Genet. 56:1995;993-998.
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(1995)
Am J Hum Genet
, vol.56
, pp. 993-998
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Cook, E.H.1
Stein, M.A.2
Krasowski, M.D.3
Cox, N.J.4
Olkon, D.M.5
Kieffer, J.E.6
Leventhal, B.L.7
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48
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0030133840
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Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder
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LaHosta GJ, Swanson JM, Wigal SB, Glabe C, King N, Kennedy JL, Wigal T. Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry. 1:1996;121-124.
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(1996)
Mol Psychiatry
, vol.1
, pp. 121-124
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LaHosta, G.J.1
Swanson, J.M.2
Wigal, S.B.3
Glabe, C.4
King, N.5
Kennedy, J.L.6
Wigal, T.7
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49
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0030844034
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Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism
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The previously reported association of ADHD and the dopamine transporter [47] was replicated in this study of 40 ADHD children diagnosed in Dublin, Ireland. In the families of the probands, DNA was obtained from 68 parents. Two alleles were detected of the 40 base pair (bp) VNTR in this sample: the 440bp allele with a relative frequency of 0.29 and the 480 bp allele with a relative frequency of 0.71. HRR (haplotype relative risk) analysis of 62 informative parents (124 alleles) revealed a significant association of the dopamine transporter polymorphism and diagnosis of ADHD, due to higher than expected transmission of the 480 bp allele (52 of 92) and lower than expected transmission of the 440 bp allele (10 of 32). of outstanding interest
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Gill M, Daly G, Heron S, Hawl Z, Fitzgerald M. Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry. 2:1997;311-313 The previously reported association of ADHD and the dopamine transporter [47] was replicated in this study of 40 ADHD children diagnosed in Dublin, Ireland. In the families of the probands, DNA was obtained from 68 parents. Two alleles were detected of the 40 base pair (bp) VNTR in this sample: the 440bp allele with a relative frequency of 0.29 and the 480 bp allele with a relative frequency of 0.71. HRR (haplotype relative risk) analysis of 62 informative parents (124 alleles) revealed a significant association of the dopamine transporter polymorphism and diagnosis of ADHD, due to higher than expected transmission of the 480 bp allele (52 of 92) and lower than expected transmission of the 440 bp allele (10 of 32). of outstanding interest.
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(1997)
Mol Psychiatry
, vol.2
, pp. 311-313
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Gill, M.1
Daly, G.2
Heron, S.3
Hawl, Z.4
Fitzgerald, M.5
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50
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15144354766
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Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): A family-based approach
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The previously reported association of ADHD and the dopamine D4 receptor [48] was replicated in this study of 52 parent - child triads identified by diagnosis of probands with a refined phenotype of ADHD/HKD (the combined type without comorbidities requiring treatment, who had demonstrated a clinical response to stimulant medication). Haplotype relative risk (HRR) analysis revealed a significant association of the dopamine receptor D4 polymorphism and diagnosis of ADHD/HKD, due to a higher than expected transmission of the 7-repeat allele (29 of 47). of outstanding interest
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Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T, Lerner M, Williams L, LaHoste GJ, Wigal S. Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry. 3:1998;38-41 The previously reported association of ADHD and the dopamine D4 receptor [48] was replicated in this study of 52 parent - child triads identified by diagnosis of probands with a refined phenotype of ADHD/HKD (the combined type without comorbidities requiring treatment, who had demonstrated a clinical response to stimulant medication). Haplotype relative risk (HRR) analysis revealed a significant association of the dopamine receptor D4 polymorphism and diagnosis of ADHD/HKD, due to a higher than expected transmission of the 7-repeat allele (29 of 47). of outstanding interest.
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(1998)
Mol Psychiatry
, vol.3
, pp. 38-41
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Swanson, J.M.1
Sunohara, G.A.2
Kennedy, J.L.3
Regino, R.4
Fineberg, E.5
Wigal, T.6
Lerner, M.7
Williams, L.8
LaHoste, G.J.9
Wigal, S.10
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