Initial evidence that OPRM1 genotype moderates ventral and dorsal striatum functional connectivity during alcohol cues.
- Authors
- Ray, Lara A; Courtney, Kelly E; Hutchison, Kent E; Mackillop, James; Galvan, Adriana; Ghahremani, Dara G
- Year
- 2014
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 23876228
- DOI
- 10.1111/acer.12136
- PMCID
- PMC3808494
BACKGROUND: Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral striatal functional connectivity during alcohol-cue processing as a function of the A118G single-nucleotide polymorphism of the mu-opioid receptor (OPRM1) gene. METHODS: Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional magnetic resonance imaging, while performing an alcohol taste-cues task. Psychophysiological interaction analyses investigated associations of the OPRM1 genotype with ventral and dorsal striatum functional connectivity, using the ventral striatum and the caudate as the seed region, respectively. RESULTS: Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i) greater activation of the insula and orbitofrontal cortex and (ii) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues. CONCLUSIONS: These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.
Urge to drink ratings across taste delivery blocks for alcohol and water cues. There was a significant main effect of condition (alcohol vs. water) (p < .01) and a main effect of time, such that urge ratings increased across trial (p <.01). However, there was no significant Condition × Time interaction (p = .65).
Schematic of a single taste cue trial and model. A rest period immediately followed the taste delivery period for 6 s, wherein “Rest” was presented visually. A single urge question (“What is your urge to drink alcohol?”) was presented for a total of 12 s at the end of the rest period, followed by “Ready?” for 2 s.
Brain activation within the alcohol- versus water-cue contrast (see Table 3 for full list of regions). Z-statistic maps are whole-brain cluster-corrected, Z>2.3, p=0.05. The threshold for the statistical map was decreased for visualization purposes. Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
Brain activation moderated by OPRM1 genotype (AG/GG vs. AA) within the alcohol- versus water-cue contrast. The left insula was a primary area of activation that found to be greater for G-allele carriers (see Table 3 for full list of regions). Z-statistic maps are whole-brain cluster-corrected, Z>1.96, p=0.05. The threshold for the statistical map was decreased for visualization purposes. Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
Results of the negative main effect functional connectivity analysis indicating areas of decreased functional connectivity to the ventral striatum during the presentation of alcohol- versus water-cues (whole-brain cluster-corrected at Z>1.96, p<0.05). Brain regions showing decreased functional connectivity were largely posterior, and included the occipital and cuneal cortices. Results are from a psychophysiological interaction (PPI) analysis using the right ventral striatum (including the nucleus accumbens) as an anatomically defined region of interest determined for each participant individually (see methods). Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
Results of the negative main effect functional connectivity analysis indicating areas of decreased functional connectivity to the dorsal striatum (caudate) during the presentation of alcohol- versus water-cues (whole-brain cluster-corrected at Z>1.96, p<0.05). Brain regions showing decreased functional connectivity were largely posterior, and included the precuneus and occipital cortices. Results are from a psychophysiological interaction (PPI) analysis using the right dorsal striatum (caudate) as an anatomically defined region of interest determined for each participant individually (see methods). Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
Results of functional connectivity analysis revealed negative fronto-ventral striatal connectivity during the presentation of alcohol- versus water-cues was moderated by OPRM1 genotype (AG/GG vs. AA). The seed ROI is presented in blue. Brain regions whose negative connectivity with the right ventral striatum is greater for G-allele carriers as compared to A-allele homozygotes include the insula, frontal medial cortex, superior parietal lobule, thalamus, putamen, and paracingulate gyrus (whole-brain cluster-corrected at Z>1.96, p<0.05). Results are from a psychophysiological interaction (PPI) analysis using the right ventral striatum (including the nucleus accumbens) as an anatomically defined region of interest determined for each participant individually (see methods). No regions were found to be more positively functionally connected with the ventral striatum in the G-allele carriers as compared to the A-allele homozygotes. Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
Results of functional connectivity analysis revealed negative fronto-dorsal striatal connectivity during the presentation of alcohol- versus water-cues was moderated by OPRM1 genotype (AG/GG vs. AA). The seed ROI is presented in blue. Brain regions whose negative connectivity with the right dorsal striatum (caudate) is greater for G-allele carriers as compared to A-allele homozygotes include the insula, orbitofrontal cortex, paracingulate gyrus, and subcallosal cortex (whole-brain cluster-corrected at Z>1.96, p<0.05). Results are from a psychophysiological interaction (PPI) analysis using the right dorsal striatum (caudate) as an anatomically defined region of interest determined for each participant individually (see methods). No regions were found to be more positively functionally connected with the caudate in the G-allele carriers as compared to the A-allele homozygotes. Coordinates are in MNI space, and the brain is displayed in radiological convention (left = right).
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