Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Participants
Population-based cohort.
Characteristic or Measure | Baseline (N=1,963) | 2-Year Follow-Up (N=1,518) | ||
---|---|---|---|---|
N | % | N | % | |
Male | 952 | 48.5% | 728 | 48.0% |
Mean | SD | Mean | SD | |
Age (years) | 14.43 | 0.40 | 16.47 | 0.57 |
Hyperactivity-inattention subscale on parent SDQ | ||||
Total score | 2.97 | 2.29 | 2.39 | 2.05 |
Hyperactivity-impulsivity score | 0.70 | 1.05 | 0.47 | 0.87 |
Inattention score | 2.27 | 1.65 | 1.92 | 1.57 |
N | % | N | % | |
ADHD categories by hyperactivity-inattention total scoreb | ||||
Normal | 1,690 | 86.1 | 1,394 | 91.8 |
Borderline | 107 | 5.5 | 64 | 4.1 |
Abnormal | 166 | 8.5 | 62 | 4.1 |
Mean | SD | |||
Delay discounting | –1.98 | 0.61 | ||
Working memory | 19.45 | 14.00 | ||
Intrasubject variabilityc | 119.38 | 30.96 | ||
Stop-signal reaction timec | 186.43 | 61.90 |
Clinical cohort.
Measurements
ADHD.
Delay discounting.
Working memory.
Intrasubject variability and stop-signal reaction time.
Structural MRI
Genetic Data
Statistical Analysis
Voxel-wise brain-wide association analysis.
Neuropsychological association analysis.
Prospective association analysis.
Polygenic analysis.
Validation.
Results
Descriptive Statistics
ADHD Symptoms | Gray Matter Volume | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Total Score | Hyperactivity-Impulsivity | Inattention | Prefrontal Cluster | Posterior occipital Cluster | ||||||
Measure | r | 95% CI | r | 95% CI | r | 95% CI | r | 95% CI | r | 95% CI |
Working memoryb | 0.19*** | 0.15, 0.24 | 0.09*** | 0.05, 0.14 | 0.21*** | 0.16, 0.25 | −0.04 | −0.08, 0.01 | −0.08*** | −0.12, −0.03 |
Delay discountingb | 0.13*** | 0.08, 0.17 | 0.06** | 0.02, 0.11 | 0.14*** | 0.09.0.18 | −0.07** | −0.11, −0.02 | −0.06* | −0.10, −0.01 |
Intrasubject variabilityc | 0.14*** | 0.10, 0.19 | 0.09*** | 0.04, 0.14 | 0.14*** | 0.10, 0.19 | −0.05* | −0.10, −0.01 | −0.06** | −0.11, −0.01 |
Working memory corrected for delay discounting and intrasubject variability | 0.16*** | 0.12, 0.21 | 0.07** | 0.03, 0.12 | 0.18*** | 0.13, 0.22 | −0.04 | −0.09, 0.005 | −0.07** | −0.11, −0.02 |
Delay discounting corrected for working memory and intrasubject variability | 0.10*** | 0.05, 0.15 | 0.05* | 0.001, 0.10 | 0.11*** | 0.06, 0.15 | −0.05* | −0.09, −0.002 | −0.05* | −0.09, −3.3e–4 |
Intrasubject variability corrected for working memory and delay discounting | 0.12*** | 0.08, 0.17 | 0.08** | 0.03, 0.13 | 0.12*** | 0.07, 0.16 | −0.04 | −0.09, 0.005 | −0.05* | −0.10, −0.01 |
Neuroanatomical Correlates of Inattention in a Population-Based Cohort
Neuroanatomical Correlates of Inattention Selectively Associated With Working Memory, Intrasubject Variability, or Delay Discounting
Prospective Associations With Inattention 2 Years Later
Step | Category | Independent Variable | R2 | ΔR2 | pea | βfb | tfc | pfd |
---|---|---|---|---|---|---|---|---|
Step 1 | Covariates | Sex | 0.412 | 0.412 | <0.001 | 0.073 | 2.86 | 0.004 |
Handedness | 0.016 | 0.79 | 0.430 | |||||
Total intracranial volume | 0.010 | 0.375 | 0.708 | |||||
Inattention at age 14 | 0.608 | 28.45 | <0.001 | |||||
Site 1 | 0.018 | 0.66 | 0.508 | |||||
Site 2 | 0.050 | 1.80 | 0.072 | |||||
Site 3 | 0.068 | 2.57 | 0.010 | |||||
Site 4 | 0.065 | 2.47 | 0.014 | |||||
Site 5 | 0.010 | 0.36 | 0.721 | |||||
Site 6 | 0.038 | 1.44 | 0.151 | |||||
Site 7 | 0.036 | 1.37 | 0.170 | |||||
Step 2 | Behavior | Working memory | 0.414 | 0.002 | 0.017 | 0.044 | 2.04 | 0.042 |
Step 3 | Delay discounting | 0.414 | 0.000 | 0.593 | 0.007 | 0.35 | 0.724 | |
Step 4 | Intrasubject variability | 0.415 | 0.001 | 0.164 | 0.028 | 1.31 | 0.190 | |
Step 5 | Brain structure | Gray matter volume in prefrontal cluster | 0.415 | 0.000 | 0.685 | 0.047 | 1.88 | 0.060 |
Step 6 | Gray matter volume in posterior occipital cluster | 0.42 | 0.005 | <0.001 | –0.083 | –3.55 | <0.001 |
Associations of Neuropsychological and Neuroanatomical Intermediate Phenotypes With Polygenic Risk for ADHD
Validation Using an ADHD Clinical Cohort
Medication Effects
Discussion
Conclusions
Acknowledgments
Footnote
Supplementary Material
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