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Beyond the Dual Pathway Model: Evidence for the Dissociation of Timing, Inhibitory, and Delay-Related Impairments in Attention-Deficit/Hyperactivity Disorder

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Objective

The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD.

Method

Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured.

Results

Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings.

Conclusion

The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples.

Section snippets

Participants

Seventy-one families with an ADHD child participated in the Southampton arm of IMAGE.51 Seventy-one ADHD probands with a combined type diagnosis (mean [M] = 12.03 years, SD = 2.34 years), 65 unaffected siblings (M = 11.46 years, SD = 3.19 years) and 50 non-ADHD controls (M = 12.15 years, SD = 2.25 years) were included in the key analyses. Six siblings had ADHD and were excluded from the case–control and familiality analyses. Cases (between 6 and 17 years of age) with an existing full clinical

Results

Correlations were in general larger within domains (mean r = 0.22) than between domains (mean r = 0.11) (Table 2). Correlation between putative I-EDF and TPD measures were moderate. Correlations between putative DAv measures were weak and nonspecific. WM was associated with TPD measures and DRT and MStroop. For the principal components analysis there were four factors with Eigenvalues greater than 1 (Table 3). Component 1 (17.25% variance) had high loadings for SSRT, GNG and MStroop only

Discussion

ADHD is neuropsychologically heterogeneous, with different individuals affected to different degrees in different domains.12, 21 These results extend and refine the dual pathway model of ADHD heterogeneity.12, 13, 14 To our knowledge, our data provide the first evidence that Timing, Inhibition, and Delay deficits in ADHD are dissociable from each other and that substantial subgroups of patients are affected in only one domain. The results therefore run counter to a recent suggestion that timing

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    This research was funded in part by ESRC CASE Award PTA-033-2003-00046 with Eli Lilley Ltd (to E.S.-B. and M.T. for P.B.).

    Clinical data from the participants included in this paper contributed to the IMAGE project (Faraone; National Institutes of Health grant R01 MH62873-01A1).

    Disclosure: Dr. Sonuga-Barke has served on the speakers' bureau and as a consultant for Shire and UCB Pharma. He has received research support from Janssen Cilag, Shire, Qbtech, and Flynn Pharma. He has served on the advisory board for Shire, Flynn Pharma, UCB Pharma, and Astra Zeneca. He has received conference support from Shire. Dr. Thompson has received education sponsorship from Eli Lilly and Janssen Cilag. She has received unrestricted research grants from Eli Lilly, Janssen Cilag, UCB Pharma, and Shire. She has served on the advisory board for Eli Lilly, UCB Pharma, and Shire. She has received drug trial support from Eli Lilly and Janssen Cilag. She has received lecture fees from Eli Lilly and Janssen Cilag. She has received funding for the support of Ph.D. students from Eli Lilly and Janssen Cilag. Dr. Bitsakou reports no biomedical financial interests or potential conflicts of interest.

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