Towards an understanding of unique and shared pathways in the psychopathophysiology of ADHD

Developmental Science

Volumn 8, Issue 2, 2005, Pages 132-140

  Banaschewski, Tobias ^a   Mollis, Chris ^b   Oosterlaan, Jaap ^c   Roeyers, Herbert ^d   Rubia, Katya ^e   Willcutt, Erik ^f   Taylor, Eric ^e  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^c VU UNIVERSITY AMSTERDAM   (Netherlands)

^d GHENT UNIVERSITY   (Belgium)

^e KING'S COLLEGE LONDON   (United Kingdom)

^f UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; ATTENTION DEFICIT DISORDER; AUTISM; CONDUCT DISORDER; DYSLEXIA; EFFERENT NERVE; GENETICS; HUMAN; MOTIVATION; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PSYCHOLOGICAL ASPECT; SCHIZOPHRENIA; TIME PERCEPTION;

ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; AUTISTIC DISORDER; CONDUCT DISORDER; DYSLEXIA; EFFERENT PATHWAYS; HUMANS; MOTIVATION; SCHIZOPHRENIA; TIME PERCEPTION;

EID: 14844292638     PISSN: 1363755X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1467-7687.2005.00400.x     Document Type: Article

References (85)

1. Aronowitz, B., Liebowitz, M., Hollander, E., Fazzini, E., Durlach-Misteli, C., Frenkel, M., Mosovich, S., Garfinkel, R., Saoud, J., DelBene, D., Cohen, L., Jaeger, A., & Rubin, A.L. (1994). Neuropsychiatrie and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder. Journal of Neuropsychiatry and Clinical Neurosciences, 6 (3), 245-249.
2. Banaschewski, T., Brandeis, D., Heinrich, H., Albrecht, B., Brunner, E., & Rothenberger, A. (2003a). Association of ADHD and conduct disorder - brain electrical evidence for the existence of a distinct subtype. Journal of Child Psychology and Psychiatry, 44 (3), 356-376.
3. Banaschewski, T., Brandeis, D., Heinrich, H., Albrecht, B., Brunner, E., & Rothenberger, A. (2004). Questioning inhibitory control as the specific deficit of ADHD - evidence from brain electrical activity. Journal of Neural Transmission, 111, 841-864; published on-line 24 October 2003, DOI 10.1007/s00702-003-0040-8.
4. Barkley, R.A. (1997). Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin, 121 (1), 65-94.
5. Barkley, R.A., Grodzinsky, G., & DuPaul, G.J. (1992). Frontal lobe functions in attention deficit disorder with and without hyperactivity: a review and research report. Journal of Abnormal Child Psychology, 20 (2), 163-188.
6. Baron-Cohen, S., Ring, H.A., Wheelwright, S., Bullmore, E.T., Brammer, M.J., Simmons, A., & Williams, S.C. (1999). Social intelligence in the normal and autistic brain: an fMRI study. European Journal of Neuroscience, 11 (6), 1891-1898.
7. Bauer, L.O., & Hesselbrock, V.M. (1999). P300 decrements in teenagers with conduct problems: implications for substance abuse risk and brain development. Biological Psychiatry, 46 (2), 263-272.
8. Biederman, J., Faraone, S.V., Keenan, K., Benjamin, J., Krifcher, B., Moore, C., Sprich-Buckminster, S., Ugaglia, K., Jellinek, M.S., Steingard, R., Spencer, T., Norman, D., Kolodny, R., Kraus, I., Perrin, J., Keller, M.B., & Tsuang, M.T. (1992). Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples. Archives of General Psychiatry, 49 (9), 728-738.
9. Booth, R., Charlton, R., Hughes, C., & Happe, F. (2003). Disentangling weak coherence and executive dysfunction: planning drawing in autism and attention-deficit/hyperactivity disorder. Philosophical Transactions of the Royal Society of London Series B - Biological Sciences, 358 (1430), 387-392.
10. Bramon, R.A., Rabe-Hesketh, S., Murray, R.M., & Frangou, S. (2004). Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophrenia Research, 70 (2-3), 315-329.
11. Brandeis, D., Banaschewski, T., Baving, L., Georgiewa, P., Blanz, B., Warnke, A., Steinhausen, H.C., Rothenberger, A., & Scheuerpflug, P. (2002). Multicenter P300 brain mapping of impaired attention to cues in hyperkinetic children. Journal of the American Academy of Child and Adolescent Psychiatry, 41 (8), 990-998.
12. Breier, J.I., Simos, P.G., Fletcher, J.M., Castillo, E.M., Zhang, W., & Papanicolaou, A.C. (2003). Abnormal activation of temporoparietal language areas during phonetic analysis in children with dyslexia. Neuropsychology, 17 (4), 610-621.
13. Castellanos, F.X., Lee, P.P., Sharp, W., Jeffries, N.O., Greenstein, D.K., Clasen, L.S., Blumenthal, J.D., James, R.S., Ebens, C.L., Walter, J.M., Zijdenbos, A., Evans, A.C., Giedd, J.N., & Rapoport, J.L. (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Medical Association, 288 (14), 1740-1748.
14. Castellanos, F.X., & Tannock, R. (2002). Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nature Reviews. Neuroscience, 3 (8), 617-628.
15. Clark, C., Prior, M., & Kinsella, G.J. (2000). Do executive function deficits differentiate between adolescents with ADHD and oppositional defiant/conduct disorder? A neuropsychological study using the six elements test and Hayling sentence completion test. Journal of Abnormal Child Psychology, 28 (5), 403-414.
16. Coghill, D., Nigg, J., Rothenberger, A., Sonuga-Barke, E., & Tannock, R. (2005). Whither causal models in the neuroscience of ADHD? Developmental Science, 8 (2), 105-114.
17. Crosbie, J., & Schachar, R. (2001). Deficient inhibition as a marker for familial ADHD. American Journal of Psychiatry, 158(11), 1884-1890.
18. Faraone, S.V., Biederman, J., Mennin, D., Russell, R., & Tsuang, M.T. (1998). Familial subtypes of attention deficit hyperactivity disorder: a 4-year follow-up study of children from antisocial-ADHD families. Journal of Child Psychology and Psychiatry, 39 (7), 1045-1053.
19. Fletcher, P.C. (2000). The functional neuroimaging of memory disorders. In J.C. Mazziotta, A.W. Toga & R.S.J. Frackowiak (Eds.), Brain mapping: The disorders (pp. 201-215). San Diego: Academic Press.
20. Geurts, H.M., Verte, S., Oosterlaan, J., Roeyers, H., & Sergeant, J.A. (2004). How specific are executive functioning deficits in attention deficit hyperactivity disorder and autism? Journal of Child Psychology and Psychiatry, 45 (4), 836-854.
21. Gold, J.M., Carpenter, C., Randolph, C., Goldberg, T.E., & Weinberger, D.R. (1997). Auditory working memory and Wisconsin card sorting test performance in schizophrenia. Archives of General Psychiatry, 54 (2), 159-165.
22. Goldman-Rakic, P.S. (1998). The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. In A.C. Roberts, T.W. Robbins & L. Weiskrantz (Eds.), The prefrontal cortex: executive and cognitive functions (pp. 87-102). Oxford: Oxford University Press.
23. Gordon, C.T., Frazier, J.A., McKenna, K., Giedd, J., Zametkin, A., Zahn, T., Hommer, D., Hong, W., Kaysen, D., Albus, K.E., & Rapoport, J.L. (1994). Childhood-onset schizophrenia: an NIMH study in progress. Schizophrenia Bulletin, 20 (4), 697-712.
24. Harrison, P.J., & Owen, M.J. (2003). Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet, 361 (9355), 417-419.
25. Hollis, C. (1995). Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. British Journal of Psychiatry, 166 (4), 489-495.
26. Kalff, A.C., Hendriksen, J.G., Kroes, M., Vies, J.S., Steyaert, J., Feron, F.J., van Zeben, T.M., & Jolles, J. (2002). Neurocognitive performance of 5- and 6-year-old children who met criteria for attention deficit/hyperactivity disorder at 18 months follow-up: results from a prospective population study. Journal of Abnormal Child Psychology, 30 (6), 589-598.
27. Karatekin, C., & Asarnow, R.F. (1998). Working memory in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder. Psychiatry Research, 80 (2), 165-176.
28. Kempton, S., Vance, A., Maruff, P., Luk, E., Costin, J., & Pantelis, C. (1999). Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children. Psychological Medicine, 29 (3), 527-538.
29. Klingberg, T., Hedehus, M., Temple, E., Salz, T., Gabrieli, J.D., Moseley, M.E., & Poldrack, R.A. (2000). Microstructure of temporo-parietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging. Neuron, 25 (2), 493-500.
30. Klorman, R., Hazel-Fernandez, L.A., Shaywitz, S.E., Fletcher, J.M., Marchione, K.E., Holahan, J.M., Stuebing, K.K., & Shaywitz, B.A. (1999). Executive functioning deficits in attention-deficit/hyperactivity disorder are independent of oppositional defiant or reading disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 38(9), 1148-1155.
31. Kooijmans, R., Scheres, A., & Oosterlaan, J. (2000). Response inhibition and measures of psychopathology: a dimensional analysis. Neuropsychology, Development, and Cognition. Section C, Child Neuropsychology, 6 (3), 175-184.
32. Kuntsi, J., Oosterlaan, J., & Stevenson, J. (2001). Psychological mechanisms in hyperactivity: I response inhibition deficit, working memory impairment, delay aversion, or something else? Journal of Child Psychology and Psychiatry, 42 (2), 199-210.
33. Loo, S.K., Fisher, S.E., Francks, C., Ogdie, M.N., MacPhie, I.L., Yang, M., McCracken, J.T., McGough, J.J., Nelson, S.F., Monaco, A.P., & Smalley, S.L. (2004). Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/ hyperactivity disorder: unique and shared genetic effects. Molecular Psychiatry, 9 (5), 485-493.
34. MacLeod, D., & Prior, M. (1996). Attention deficits in adolescents with ADHD and other clinical groups. Child Neuropsychology, 2, 1-10.
35. Marcus, J., Hans, S.L., Nagler, S., Auerbach, J.G., Mirsky, A.F., & Aubrey, A. (1987). Review of the NIMH Israeli Kibbutz-City Study and the Jerusalem Infant Development Study. Schizophrenia Bulletin, 13 (3), 425-438.
36. Mirowsky, J., & Ross, C.E. (1989). Psychiatric diagnosis as reified measurement. Journal of Health and Social Behavior, 30 (1), 11-25; discussion, 26-40.
37. Miyake, A., Friedman, N.P., Emerson, M.J., Witzki, A.H., Howerter, A., & Wager, T.D. (2000). The unity and diversity of executive functions and their contributions to complex 'frontal lobe' tasks: a latent variable analysis. Cognitive Psychology, 41 (1), 49-100.
38. Nicolson, R.I., Fawcett, A.J., & Dean, P. (2001). Developmental dyslexia: the cerebellar deficit hypothesis. Trends in Neurosciences, 24 (9), 508-511.
39. Nigg, J.T. (2001). Is ADHD a disinhibitory disorder? Psychological Bulletin, 127 (5), 571-598.
40. Nyden, A., Gillberg, C., Hjelmquist, E., & Heiman, M. (1999). Executive function/attention deficits in boys with Asperger syndrome, attention disorder and reading/writing disorder. Autism, 3, 213-228.
41. Oades, R.D., Dittmann-Balcar, A., Schepker, R., Eggers, C., & Zerbin, D. (1996). Auditory event-related potentials (ERPs) and mismatch negativity (MMN) in healthy children and those with attention-deficit or tourette/tic symptoms. Biological Psychiatry, 43 (2), 163-185.
42. Olincy, A., Ross, R.G., Harris, J.G., Young, D.A., McAndrews, M.A., Cawthra, E., McRae, K.A., Sullivan, B., Adler, L.E., & Freedman, R. (2000). The P50 auditory event-evoked potential in adult attention-deficit disorder: comparison with schizophrenia. Biological Psychiatry, 47 (11), 969-977.
43. Oosterlaan, J., Logan, G.D., & Sergeant, J.A. (1998). Response inhibition in ADHD, CD, comorbid ADHD + CD, anxious, and control children: a meta-analysis of studies with the stop task. Journal of Child Psychology and Psychiatry, 39 (3), 411-425.
44. Oosterlaan, J., & Sergeant, J.A. (1998). Effects of reward and response cost on response inhibition in ADHD, disruptive, anxious, and normal children. Journal of Abnormal Child Psychology, 26 (3), 161-174.
45. Ozonoff, S., & Jensen, J. (1999). Brief report: specific executive function profiles in three neurodevelopmental disorders. Journal of Autism and Developmental Disorders, 29 (2), 171-177.
46. Pennington, B.F., & Ozonoff, S. (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry, 37 (1), 51-87.
47. Pennington, B.F., Groisser, D., & Welsh, M.C. (1993). Contrasting cognitive deficits in Attention Deficit Hyperactivity Disorder versus Reading Diability. Developmental Psychology, 29, 511-523.
48. Pennington, B.F., Filipek, P.A., Lefly, D., Churchwell, J., Kennedy, D.N., Simon, J.H., Filley, C.M., Galaburda, A., Alarcon, M., & DeFries, J.C. (1999). Brain morphometry in reading-disabled twins. Neurology, 53 (4), 723-729.
49. Piven, J., Arndt, S., Bailey, J., & Andreasen, N. (1996). Regional brain enlargement in autism: a magnetic resonance imaging study. Journal of the American Academy of Child and Adolescent Psychiatry, 35 (4), 530-536.
50. Purvis, K.L., & Tannock, R. (2000). Phonological processing, not inhibitory control, differentiates ADHD and reading disability. Journal of the American Academy of Child and Adolescent Psychiatry, 39 (4), 485-494.
51. Rapoport, J.L., Giedd, J., Kumra, S., Jacobsen, L., Smith, A., Lee, P., Nelson, J., & Hamburger, S. (1997). Childhood-onset schizophrenia. Progressive ventricular change during adolescence. Archives of General Psychiatry, 54 (10), 897-903.
52. Ross, R.G., Olincy, A., Harris, J.G., Sullivan, B., & Radant, A. (2000). Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults with schizophrenia, ADHD, and a normal comparison group. Biological Psychiatry, 48 (3), 197-203.
53. Rothenberger, A., Banaschewski, T., Heinrich, H., Moll, G.H., Schmidt, M.H., & van't Klooster, B. (2000). Comorbidity in ADHD-children: effects of coexisting conduct disorder or tic disorder on event-related brain potentials in an auditory selective-attention task. European Archives of Psychiatry and Clinical Neuroscience, 250 (2), 101-110.
54. Rubia, K. (2002). The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia. Behavioural Brain Research, 130 (1-2), 47-56.
55. Rubia, K., Overmeyer, S., Taylor, E., Brammer, M., Williams, S.C., Simmons, A., & Bullmore, E.T. (1999a). Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. American Journal of Psychiatry, 156 (6), 891-896.
56. Rubia, K., Sergeant, J., Taylor, A., & Taylor, E. (1999b). Synchronization, anticipation and consistency of motor timing in dimensionally defined children with Attention Deficit Hyperactivity Disorder. Perceptual and Motor Skills, 89, 1237-1258.
57. Rucklidge, J.J., & Tannock, R. (2002). Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender. Journal of Child Psychology and Psychiatry, 43 (8), 988-1003.
58. Rund, B.R., Oie, M., & Sundet, K. (1996). Backward-masking deficit in adolescents with schizophrenic disorders or attention deficit hyperactivity disorder. American Journal of Psychiatry, 153 (9), 1154-1157.
59. Sagvolden, T., Johansen, E.B., Aase, H., & Russell, V.A. (in press). A dynamic developmental theory of Attention-Deficit/ Hyperactivity Disorder (ADHD) predominantly hyperactive/ impulsive and combined subtypes. Behavioral and Brain Sciences.
60. Saitoh, O., Courchesne, E., Egaas, B., Lincoln, A.J., & Schreibman, L. (1995). Cross-sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalities. Neurology, 45 (2), 317-324.
61. Salisbury, D.F., Shenton, M.E., Sherwood, A.R., Fischer, I.A., Yurgelun-Todd, D.A., Tohen, M., & McCarley, R.W. (1998). First-episode schizophrenic psychosis differs from first-episode affective psychosis and controls in P300 amplitude over left temporal lobe. Archives of General Psychiatry, 55 (2), 173-180.
62. Schachar, R., Mota, V.L., Logan, G.D., Tannock, R., & Klim, P. (2000). Confirmation of an inhibitory control deficit in attention-deficit/ hyperactivity disorder. Journal of Abnormal Child Psychology, 28 (3), 227-235.
63. Sergeant, J.A., & Scholten, C.A. (1985). On resource strategy limitations in hyperactivity: cognitive impulsivity reconsidered. Journal of Child Psychology and Psychiatry, 26 (1), 97-109.
64. Sergeant, J.A., Oosterlaan, J., & Van der Meere, J.J. (1999). Information processing and energetic factors in attention-deficit/hyperactivity disorder. In H.C. Quay & A. Hogan (Eds.), Handbook of disruptive behavior disorders (pp. 75-104). New York: Plenum Press.
65. Sergeant, J.A., Geurts, H., & Oosterlaan, J. (2002). How specific is a deficit of executive functioning for attention-deficit/ hyperactivity disorder? Behavioural Brain Research, 130 (1-2), 3-28.
66. Sergeant, J.A., Geurts, H., Huijbregts, S., Scheres, A., & Oosterlaan, J. (2003). The top and the bottom of ADHD: a neuropsychological perspective. Neuroscience & Biobehavioral Reviews, 27 (7), 583-592.
67. Shastry, B.S. (2003). Molecular genetics of autism spectrum disorders. Journal of Human Genetics, 48 (10), 495-501.
68. Simonoff, E. (2001). Genetic influences on conduct disorder. In J. Hill & B. Maughan (Eds.), Conduct disorder in childhood and adolescence (pp. 202-234). Cambridge: Cambridge University Press.
69. Smalley, S.L., Kustanovich, V., Minassian, S.L., Stone, J.L., Ogdie, M.N., McGough, J.J., McCracken, J.T., MacPhie, I.L., Francks, C., Fisher, S.E., Cantor, R.M., Monaco, A.P., & Nelson, S.F. (2002). Genetic linkage of attention-deficit/ hyperactivity disorder on chromosome 16p13, in a region implicated in autism. American Journal of Human Genetics, 71 (4), 959-963.
70. Smith, A., Taylor, E., Rogers, J.W., Newman, S., & Rubia, K. (2002). Evidence for a pure time perception deficit in children with ADHD. Journal of Child Psychology and Psychiatry, 43 (4), 529-542.
71. Solanto, M.V., Abikoff, H., Sonuga-Barke, E., Schachar, R., Logan, G.D., Wigal, T., Hechtman, L., Hinshaw, S., & Turkel, E. (2001). The ecological validity of delay aversion and response inhibition as measures of impulsivity in ADHD: a supplement to the NIMH multimodal treatment study of ADHD. Journal of Abnormal Child Psychology, 29 (3), 215-228.
72. Sonuga-Barke, E.J. (2002). Psychological heterogeneity in ADHD - a dual pathway model of behaviour and cognition. Behavioural Brain Research, 130 (1-2), 29-36.
73. Sowell, E.R., Thompson, P.M., Welcome, S.E., Henkenius, A.L., Toga, A.W., & Peterson, B.S. (2003). Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Lancet, 362 (9397), 1699-1707.
74. Stevenson, J., Pennington, B.F., Gilger, J.W., DeFries, J.C., & Gillis, J.J. (1993). Hyperactivity and spelling disability: testing for shared genetic aetiology. Journal of Child Psychology and Psychiatry, 34 (7), 1137-1152.
75. Tallal, P. (1980). Auditory temporal perception, phonics, and reading disabilities in children. Brain and Language, 9 (2), 182-198.
76. Tannock, R. (1998). Attention deficit hyperactivity disorder: advances in cognitive, neurobiological, and genetic research. Journal of Child Psychology and Psychiatry, 39 (1), 65-99.
77. Tannock, R., Martinussen, R., & Frijters, J. (2000). Naming speed performance and stimulant effects indicate effortful, semantic processing deficits in attention-deficit/hyperactivity disorder. Journal of Abnormal Child Psychology, 28 (3), 237-252.
78. Thapar, A., Holmes, J., Poulton, K., & Harrington, R. (1999). Genetic basis of attention deficit and hyperactivity. British Journal of Psychiatry, 174, 105-111.
79. Thompson, P.M., Vidal, C., Giedd, J.N., Gochman, P., Blumenthal, J., Nicolson, R., Toga, A.W., & Rapoport, J.L. (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 98 (20), 11650-11655.
80. Vaidya, C.J., Austin, G., Kirkorian, G., Ridlehuber, H.W., Desmond, J.E., Glover, G.H., & Gabrieli, J.D. (1998). Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proceedings of the National Academy of Sciences of the United States of America, 95 (24), 14494-14499.
81. Wagner, R.K., & Torgesen, J.K. (1987). The nature of phonological processing and its causal role in the acquisition of reading skills. Psychological Bulletin, 101, 192-212.
82. Weyandt, L.L., Rice, J.A., Linterman, I., Mitzlaff, L., & Emert, E. (1998). Neuropsychological performance of a sample of adults with ADHD, developmental reading disorder, and controls. Developmental Neuropsychology, 14, 643-656.
83. Willcutt, E.G., Pennington, B.F., & DeFries, J.C. (2000). Twin study of the etiology of comorbidity between reading disability and attention-deficit/hyperactivity disorder. American Journal of Medical Genetics, 96 (3), 293-301.
84. Willcutt, E.G., Pennington, B.F., Smith, S.D., Cardon, L.R., Gayan, J., Knopik, VS., Olson, R.K., & DeFries, J.C. (2002). Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/ hyperactivity disorder. American Journal of Medical Genetics, 114 (3), 260-268.
85. Willcutt, E.G., DeFries, J.C., Pennington, B.F., Olson, R.K., Smith, S.D., & Cardon, L.R. (2003). Genetic etiology of comorbid reading difficulties and ADHD. In R. Plomin, J.C. DeFries, P. McGuffin & I. Craig (Eds.), Behavioral genetics in a postgenomic era (pp. 227-246). Washington D.C.: American Psychological Association.