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

Christopher T Smith,Linh C Dang,Leah L Burgess,Gregory R Samanez-Larkin,Daniel T Katz,David H Zald,Scott F Perkins,Daniel O Claassen,Ronald L Cowan,H Charles Manning,Michael L Nickels,M Danica San Juan

doi:10.1038/s41398-018-0328-y

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 (BPND) using the tracer 18F-FE-PE2I in 47 healthy adult subjects and examined relations between BPND 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 BPND in each striatal subregion showed nominal negative associations with total BIS-11 but not TPQ-NS. At the subscale level, VS DAT BPND was significantly associated with BIS-11 motor impulsivity (e.g., taking actions without thinking) after correction for multiple comparisons. VS DAT BPND 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.

Highlights

Impulsivity is a transdiagnostic feature of psychopathology and is a prominent symptom of externalizing disorders, including attention-deficit/ hyperactivity disorder (ADHD), conduct disorder, antisocial personality disorder, and substance/alcohol use disorders
With the higher spatial resolution afforded by positron emission tomography (PET), we focused our FE-PE2I analysis on striatal subdivisions, which extends previous single photon emission computed tomography (SPECT) work that did not examine ventral striatum (VS) DAT28,29,42,43
The pattern of results is similar to past studies, as previous FE-PE2I PET studies have reported higher SRTM BPND in putamen relative to caudate[46,48] and immunocytochemical localization of dopamine transporter (DAT) protein in postmortem human brain has been found to be qualitatively higher in putamen than in caudate and ventral striatum[62]

Summary

Introduction

Impulsivity is a transdiagnostic feature of psychopathology and is a prominent symptom of externalizing disorders, including attention-deficit/ hyperactivity disorder (ADHD), conduct disorder, antisocial personality disorder, and substance/alcohol use disorders. The dopamine transporter (DAT), along with the norepinephrine transporter (NET1), is a key molecular target for psychostimulants (methylphenidate, (d-). These psychostimulants have been shown to reduce impulsive symptomology (e.g., response inhibition as measured by faster stop-signal reaction times[4]; physician’s rating of short attention span and hyperactivity5) and increase selfcontrol[6,7]. Given DAT’s critical role in striatal dopamine (DA) function and existing theoretical links between DA and impulsivity, individual differences in DAT are of particular interest as a potential influence on impulsivity. Individual differences in striatal DA signaling have been shown to relate to differences in trait impulsivity in human subjects[8,9].

Methods

Results

Discussion

Conclusion