Dopaminergic network differences in human impulsivity.
paper
Cited
Public
Unavailable
- Authors
- Buckholtz, Joshua W; Treadway, Michael T; Cowan, Ronald L; Woodward, Neil D; Li, Rui; Ansari, M Sib; Baldwin, Ronald M; Schwartzman, Ashley N; Shelby, Evan S; Smith, Clarence E; Kessler, Robert M; Zald, David H
- Year
- 2010
- Journal
- Science (New York, N.Y.)
- PMID
- 20671181
- DOI
- 10.1126/science.1185778
- PMCID
- PMC3161413
Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.
(A) Rendering of two separate SPMs depicting negative correlations between BIS-11 scores and D2/D3 binding and positive correlations between BIS-11 scores and amphetamine-induced DA release (corrected for multiple comparisons at the cluster-level, pcorrected < 0.05; clusters defined using a height threshold of t > 3). For the D2/D3 binding, inverse associations emerged in the DA midbrain [anteriorly in the VTA, centered at 6, β3, β11 (x, y, z; MNI space) and posteriorly in the retrorubral fields)] as well as more anteriorly in the mammillary bodies and hypothalamus (not shown). Peak coordinates for the striatal AMPH-induced DA release correlations = β16, 15, 5 (left) and 20, 23, β3 (right); cluster sizes = 167 voxels (left) and 216 voxels (right). Colorbar represents Fisher-transformed z-statistic values for the correlations (d.f. = 31). SPMs rendered on a T1-weighted MRI template brain, with cuts at z = β11 and y = 16.(B) Path analysis demonstrating that the influence of midbrain D2/D3 availability on trait impulsivity is mediated through an impact on striatal amphetamine-induced DA release. Path βAβ shows path coefficients for the effect of midbrain D2/D3 binding (cluster highlighted with red circle) on striatal DA release (left/right striatum). Path βBβ shows the path coefficient for the effect of striatal DA release on trait impulsivity (left/right striatum). Paths βCβ and βCββ show coefficients for the total (dashed line) and direct (solid line) effects of midbrain D2/D3 binding on trait impulsivity. All coefficients standardized. Sobel test for mediation: Z = β1.94, p = 0.05, with left and right striatum modeled simultaneously.
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| Title | Year | PMID |
|---|---|---|
| Dissecting impulsivity and its relationships to drug addictions. | 2014 | 24654857 |
| Genetic influences on craving for alcohol. | 2013 | 22481050 |
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