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Dopamine Reward Pathway in Adult ADHD—Reply

Dopamine Reward Pathway in Adult ADHD—Reply In Reply: In response to Dr Zametkin, we agree that ADHD may be overdiagnosed in adults because of symptom overlap with mood and anxiety disorders; however, we were cautious to avoid this and explicitly ruled out patients with psychiatric comorbidities (axis I or II diagnosis other than ADHD). In our study, experienced clinicians performed clinical interviews at both the referring sites (Drs Kollins, Wigal, and Newcorn) and imaging sites (Drs Wang and Telang). A semistructured interview was used to diagnose ADHD, which we believe is the preferred method in adults.1,2 The Hamilton rating scales were used to assess severity of anxiety and depression, and clinical judgment was used to interpret this information in ruling out anxiety and depression as comorbid disorders. Additionally, patients were excluded who had been treated for any psychiatric disorder. Although a structured approach such as the Structured Clinical Interview for DSM-IV may have been preferable to rule out comorbidity, our diagnostic approach was consistent with that of other studies of adult ADHD. Controls were also evaluated by a semistructured interview administered by an experienced clinician at the imaging location and met the same exclusion criteria but not the inclusion criteria for ADHD. Standard rating scales that assess severity of psychopathology (eg, Conners Adult ADHD Rating Scale) by definition assign low scores to controls and thus yield highly skewed distributions of scores in the population.3 The SWAN evaluates the full range (from above to below average) of underlying behavior for each ADHD item, which yields near-normal distributions of scores and captures significant variation in controls that is otherwise lost.4 The article cited by Zametkin also notes “that the SWAN scale provides a more useful description of ADHD” than conventional scales and that it “has demonstrated excellent properties in discriminating children with and without ADHD.”5 Half of our patients with ADHD were women, which is common in studies of ADHD in adults.6 We tried to match the groups on time (so they would be scanned temporarily close to one another—within a month), age, and sex, in that order. Our recruitment of controls resulted in more men than women and produced the imbalance noted by Zametkin. Restricting our analyses to only men (27 ADHD, 30 controls) yielded the same significant results, indicating that our findings are not artifacts of the sex imbalance. Drs Cortese and Castellanos discuss in detail a finding of hypothalamic abnormalities that we described as preliminary and as intriguing because, if replicated, it could hypothetically provide the neurobiological basis for the high comorbidity of ADHD with sleep disorders and obesity. Although the finding requires replication, we agree with their discussion of this possibility and appreciate their review of studies that have evaluated these factors in patients with ADHD. Back to top Article Information Financial Disclosures: Dr Swanson reported receiving support from Alza, Richwood, Shire, Celgene, Novartis, Celltech, Gliatech, Cephalon, Watson, CIBA, Janssen, and McNeil; having been on advisory boards of Alza, Richwood, Shire, Celgene, Novartis, Celltech, UCB, Gliatech, Cephalon, McNeil, and Eli Lilly; having been on the speakers bureaus of Alza, Shire, Novartis, Cellthech, UCB, Cephalon, CIBA, Janssen, and McNeil; and having consulted to Alza, Richwood, Shire, Clegene, Novarits, Celltech, UCB, Gliatech, Cephalon, Watson, CIBA, Jansen, McNeil, and Eli Lilly. Dr Newcorn reported being a recipient of research support from Eli Lilly and Ortho-McNeil Janssen; serving as a consultant, advisor, or both for Astra Zeneca, BioBehavioral Diagnostics, Eli Lilly, Novartis, Ortho-McNeil Janssen, and Shire; and serving as a speaker for Ortho-McNeil Janssen. No other financial disclosures were reported. References 1. Wigal T, Wigal S, Steinhoff K, et al. Establishing a clinical diagnosis of ADHD in adults: the Quest method. Advances in ADHD. 2007;2:17-24Google Scholar 2. Epstein JN, Kollins SH. Psychometric properties of an adult ADHD diagnostic interview. J Atten Disord. 2006;9(3):504-51416481667PubMedGoogle ScholarCrossref 3. Andrews G, Brugha T, Thase ME, et al. Dimensionality and the category of major depressive episode. In: Helzer JE, Kraemer HC, Krueger RF, eds, et al. Dimensional Approaches in Diagnostic Classification: Refining the Research Agenda for DSM-V. Arlington, VA: American Psychiatric Association; 2008 4. Polderman TJ, Derks EM, Hudziak JJ, Verhulst FC, Posthuma D, Boomsma DI. Across the continuum of attention skills: a twin study of the SWAN ADHD rating scale. J Child Psychol Psychiatry. 2007;48(11):1080-108717995483PubMedGoogle ScholarCrossref 5. Young DJ, Levy F, Martin NC, Hay DA. Attention deficit hyperactivity disorder: a Rasch analysis of the SWAN Rating Scale. Child Psychiatry Hum Dev. 2009;40(4):543-55919455417PubMedGoogle ScholarCrossref 6. Biederman J, Faraone SV, Spencer T, Wilens T, Mick E, Lapey KA. Gender differences in a sample of adults with attention deficit hyperactivity disorder. Psychiatry Res. 1994;53(1):13-297991729PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Dopamine Reward Pathway in Adult ADHD—Reply

JAMA , Volume 303 (3) – Jan 20, 2010

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References (7)

Publisher
American Medical Association
Copyright
Copyright © 2010 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2009.2000
Publisher site
See Article on Publisher Site

Abstract

In Reply: In response to Dr Zametkin, we agree that ADHD may be overdiagnosed in adults because of symptom overlap with mood and anxiety disorders; however, we were cautious to avoid this and explicitly ruled out patients with psychiatric comorbidities (axis I or II diagnosis other than ADHD). In our study, experienced clinicians performed clinical interviews at both the referring sites (Drs Kollins, Wigal, and Newcorn) and imaging sites (Drs Wang and Telang). A semistructured interview was used to diagnose ADHD, which we believe is the preferred method in adults.1,2 The Hamilton rating scales were used to assess severity of anxiety and depression, and clinical judgment was used to interpret this information in ruling out anxiety and depression as comorbid disorders. Additionally, patients were excluded who had been treated for any psychiatric disorder. Although a structured approach such as the Structured Clinical Interview for DSM-IV may have been preferable to rule out comorbidity, our diagnostic approach was consistent with that of other studies of adult ADHD. Controls were also evaluated by a semistructured interview administered by an experienced clinician at the imaging location and met the same exclusion criteria but not the inclusion criteria for ADHD. Standard rating scales that assess severity of psychopathology (eg, Conners Adult ADHD Rating Scale) by definition assign low scores to controls and thus yield highly skewed distributions of scores in the population.3 The SWAN evaluates the full range (from above to below average) of underlying behavior for each ADHD item, which yields near-normal distributions of scores and captures significant variation in controls that is otherwise lost.4 The article cited by Zametkin also notes “that the SWAN scale provides a more useful description of ADHD” than conventional scales and that it “has demonstrated excellent properties in discriminating children with and without ADHD.”5 Half of our patients with ADHD were women, which is common in studies of ADHD in adults.6 We tried to match the groups on time (so they would be scanned temporarily close to one another—within a month), age, and sex, in that order. Our recruitment of controls resulted in more men than women and produced the imbalance noted by Zametkin. Restricting our analyses to only men (27 ADHD, 30 controls) yielded the same significant results, indicating that our findings are not artifacts of the sex imbalance. Drs Cortese and Castellanos discuss in detail a finding of hypothalamic abnormalities that we described as preliminary and as intriguing because, if replicated, it could hypothetically provide the neurobiological basis for the high comorbidity of ADHD with sleep disorders and obesity. Although the finding requires replication, we agree with their discussion of this possibility and appreciate their review of studies that have evaluated these factors in patients with ADHD. Back to top Article Information Financial Disclosures: Dr Swanson reported receiving support from Alza, Richwood, Shire, Celgene, Novartis, Celltech, Gliatech, Cephalon, Watson, CIBA, Janssen, and McNeil; having been on advisory boards of Alza, Richwood, Shire, Celgene, Novartis, Celltech, UCB, Gliatech, Cephalon, McNeil, and Eli Lilly; having been on the speakers bureaus of Alza, Shire, Novartis, Cellthech, UCB, Cephalon, CIBA, Janssen, and McNeil; and having consulted to Alza, Richwood, Shire, Clegene, Novarits, Celltech, UCB, Gliatech, Cephalon, Watson, CIBA, Jansen, McNeil, and Eli Lilly. Dr Newcorn reported being a recipient of research support from Eli Lilly and Ortho-McNeil Janssen; serving as a consultant, advisor, or both for Astra Zeneca, BioBehavioral Diagnostics, Eli Lilly, Novartis, Ortho-McNeil Janssen, and Shire; and serving as a speaker for Ortho-McNeil Janssen. No other financial disclosures were reported. References 1. Wigal T, Wigal S, Steinhoff K, et al. Establishing a clinical diagnosis of ADHD in adults: the Quest method. Advances in ADHD. 2007;2:17-24Google Scholar 2. Epstein JN, Kollins SH. Psychometric properties of an adult ADHD diagnostic interview. J Atten Disord. 2006;9(3):504-51416481667PubMedGoogle ScholarCrossref 3. Andrews G, Brugha T, Thase ME, et al. Dimensionality and the category of major depressive episode. In: Helzer JE, Kraemer HC, Krueger RF, eds, et al. Dimensional Approaches in Diagnostic Classification: Refining the Research Agenda for DSM-V. Arlington, VA: American Psychiatric Association; 2008 4. Polderman TJ, Derks EM, Hudziak JJ, Verhulst FC, Posthuma D, Boomsma DI. Across the continuum of attention skills: a twin study of the SWAN ADHD rating scale. J Child Psychol Psychiatry. 2007;48(11):1080-108717995483PubMedGoogle ScholarCrossref 5. Young DJ, Levy F, Martin NC, Hay DA. Attention deficit hyperactivity disorder: a Rasch analysis of the SWAN Rating Scale. Child Psychiatry Hum Dev. 2009;40(4):543-55919455417PubMedGoogle ScholarCrossref 6. Biederman J, Faraone SV, Spencer T, Wilens T, Mick E, Lapey KA. Gender differences in a sample of adults with attention deficit hyperactivity disorder. Psychiatry Res. 1994;53(1):13-297991729PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Jan 20, 2010

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