Tobacco smoking and dopaminergic function in humans: a meta-analysis of molecular imaging studies

Abstract

Rationale: About 1.1 billion people smoke tobacco globally and tobacco-related health care costs 1.8% of GDP in many countries. The majority of people are unable to quit smoking despite pharmacological intervention, highlighting the need to understand the pathophysiology associated with tobacco smoking to aid the development of new therapeutics. The reinforcing effects of tobacco smoking are thought to be mediated by the dopamine system. However, the nature of dopamine dysfunction seen in smokers is unclear.

Objective: To determine the nature and robustness of the evidence for dopaminergic alterations in smokers.

Methods: The entire MEDLINE, EMBASE, and PsycINFO databases were searched for studies from inception date to November 18, 2018. In vivo human molecular imaging studies of dopamine measures (dopamine synthesis or release capacity, transporter levels, receptor levels) in tobacco smokers were selected. Demographic, clinical, and imaging measures were extracted from each study and meta-analyses, and sensitivity analyses were conducted.

Results: Fourteen studies met inclusion criteria comprising a total sample of 219 tobacco smokers and 297 controls. The meta-analysis showed a significant reduction in dopamine transporter availability in the smokers relative to controls with an effect size of - 0.72 ([95% CI, - 1.38 to - 0.05], p = 0.03). However, there was no difference in D2/3 receptor availability in smokers relative to controls (d = -0.16 ([95% CI, - 0.42 to 0.1], p = 0.23). There were insufficient studies for meta-analysis of other measures. However, findings from the published studies indicated blunted dopamine release and lower D1 receptor availability, while findings for dopamine synthesis capacity were inconsistent.

Conclusion: Our data indicate that striatal dopamine transporter availability is lower but D2/3 receptors are unaltered in smokers relative to controls. We discuss the putative mechanisms underlying this and their implications.

Keywords: Dopamine; Meta-analysis; Molecular imaging studies; Tobacco smoking.

Fig. 1

Studies of dopamine transporter availability in tobacco smokers relative to controls. The forest plot shows the effects sizes estimated using a random effects model and 95% confidence intervals of the difference between smokers and controls. There was an overall significant decrease in the dopamine transporter availability in smokers relative to controls with a moderate to large effect size (− 0.72 [95% CI, −1.38 to − 0.05], p < 0.05)

Fig. 2

Studies of dopamine D2/3 receptor availability in tobacco smokers relative to controls. The forest plot shows the effect sizes estimated using a random effects model and 95% confidence intervals of D2/3 receptor binding potentials. There was no significant difference in dopamine receptor availability in smokers compared to controls (− 0.16 [95% CI, − 0.42 to − 0.1], p > 0.05)