Association of dopamine transporter gene variants with childhood ADHD features in bipolar disorder
Bibliographic record
Abstract
Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) exhibit remarkably high rates of comorbidity, as well as patterns of familial co-segregation. Epidemiological data suggests that these disorders either share a common genetic architecture or that ADHD features in BD may represent an etiologically distinct subtype. We previously used the Wender Utah Rating Scale (WURS) to assess ADHD features in BD families and identified three heritable factors relating to impulsivity, mood instability, and inattention. Linkage analysis revealed a LOD score of 1.33 for the inattention factor on 5p15.3 near the dopamine transporter gene (DAT1), which has been associated with both BD and ADHD. Pharmacological evidence also suggests a role for DAT in both disorders. We have now evaluated the association of ten DAT1 variants for the WURS total score and factors in an overlapping sample of 87 BD families. Significant associations for three SNPs were observed across the WURS measures, notably for a SNP in intron 8 with the WURS total score (P = 0.007) and for variants in introns 9 and 13 with mood instability (P = 0.009 and 0.004, respectively). Analysis of an independent sample of 52 BD cases and 46 healthy controls further supported association of the intron 8 variant with mood instability (P = 0.005), and a combined analysis confirmed the associations of this SNP with WURS total score. Impulsivity and mood instability (P = 0.002, 0.007, and 8 × 10(-4), respectively). These data suggest that variants within DAT1 may predispose to a subtype of BD characterized by early prodromal features that include attentional deficits.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".