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Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults.

ABSTRACT: Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BP_ND) using the tracer ¹⁸F-FE-PE2I in 47 healthy adult subjects and examined relations between BP_ND in striatum, including its subregions: caudate, putamen, and ventral striatum (VS), and trait impulsivity (Barratt Impulsiveness Scale: BIS-11) and novelty seeking (Tridimensional Personality Questionnaire: TPQ-NS), controlling for age and sex. DAT BP_ND in each striatal subregion showed nominal negative associations with total BIS-11 but not TPQ-NS. At the subscale level, VS DAT BP_ND was significantly associated with BIS-11 motor impulsivity (e.g., taking actions without thinking) after correction for multiple comparisons. VS DAT BP_ND explained 13.2% of the variance in motor impulsivity. Our data demonstrate that DAT availability in VS is negatively related to impulsivity and suggest a particular influence of DAT regulation of dopamine signaling in VS on acting without deliberation (BIS motor impulsivity). While needing replication, these data converge with models of ventral striatal functions that emphasize its role as a key interface linking motivation to action.

SUBMITTER: Smith CT

PROVIDER: S-EPMC6286354 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults.

Smith Christopher T CT San Juan M Danica MD Dang Linh C LC Katz Daniel T DT Perkins Scott F SF Burgess Leah L LL Cowan Ronald L RL Manning H Charles HC Nickels Michael L ML Claassen Daniel O DO Samanez-Larkin Gregory R GR Zald David H DH

Translational psychiatry 20181207 1

Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BP<sub>ND</sub>) ...[more]

PMID: 30531858

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Project description:BackgroundCoffee is the most widely consumed psychostimulant worldwide. Emerging evidence indicates that coffee consumption habit significantly reduces the risk of developing Parkinson's disease (PD). However, the effect of coffee consumption on nigrostriatal dopaminergic neurodegeneration is still largely unknown. We therefore aim to investigate the role of coffee consumption in nigrostriatal dopaminergic neurodegeneration using dopamine transporter (DAT) imaging in PD and healthy controls (HC).MethodsA total of 138 PD patients and 75 HC with questionnaires about coffee consumption, and DAT scans were recruited from the Parkinson's Progression Markers Initiative cohort. Demographic, clinical, and striatal DAT characteristics were compared across subgroups of current, former, and never coffee consumers in PD and HC, respectively. Furthermore, partial correlation analyses were performed to determine whether there was a relationship between coffee cups consumed per day and striatal DAT characteristics in each striatal region. In addition, the factors that may have influenced the loss of nigrostriatal dopaminergic neurons were included in multiple linear regression analyses to identify significant contributing factors to DAT availability in each striatal region.ResultsPD patients had lower DAT availability in each striatal region than HC (p < 0.001). In PD patients, there were significant differences in DAT availability in the caudate (p = 0.008, Bonferroni corrected) across three PD subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.01) and never coffee consumers (p = 0.022). In HC, there were significant differences in DAT availability in the caudate (p = 0.031, Bonferroni uncorrected) across three HC subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.022). Moreover, correlation analysis revealed that cups per day were negatively correlated with DAT availability in the caudate in current consumers of PD patients (r = - 0.219, p = 0.047). In addition, multiple linear regression analyses showed that current coffee consumption remained an independent predictor of decreased DAT availability in the caudate in PD patients and HC.ConclusionsThis study demonstrates that current coffee consumption is associated with decreased striatal DAT availability in the caudate. However, the effects of caffeine on striatal DAT may fade and disappear after quitting coffee consumption.Trial registrationClinicalTrials.gov, NCT01141023.

Project description:Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross-sectional studies indicated certain motor and non-motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed-effect models were respectively conducted to investigate the cross-sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross-sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]-adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR-adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR-adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid-eye-movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR-adjusted p = 0.0120). Furthermore, changes in MDS-UPDRS scores and the State-Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non-motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.

Dataset Information

Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults.

Publications

Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults.

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