Effect of a History of Major Depressive Disorder on Smoking-Induced Dopamine Release
ABSTRACT Dopamine (DA) system dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). We sought to determine if cigarette smokers with a history of MDD and current mild depressive symptoms have abnormal smoking-induced DA release (measured indirectly as change in (11)C-raclopride binding potential [BP(ND)]).
Fifty-six cigarette smokers either with (n = 10) or without (n = 46) a history of MDD (MDD+ and MDD-, respectively) underwent bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography, during which they smoked a regular cigarette. Presmoking to postsmoking changes in (11)C-raclopride BP(ND) were compared between groups. Also, correlations were determined between change in BP(ND) and depression, anxiety, and withdrawal rating scale scores for the MDD+ group.
The MDD+ group had a significantly greater reduction in (11)C-raclopride BP(ND) (-16.3%) than the MDD- group (-8.4%) (analysis of covariance [ANCOVA], p = .03). Significant negative correlations were found between depression/anxiety and change in (11)C-raclopride BP(ND) (r = -.77, p < .01 and r = -.74, p = .01, respectively).
MDD+ smokers have greater smoking-induced DA release than MDD- smokers, and higher depression/anxiety levels are associated with greater smoking-induced DA release. These findings support the theory that MDD+ smokers have DA system dysfunction, including heightened smoking-induced DA release.
Full-textDOI: · Available from: Edythe D London, Aug 12, 2015
- SourceAvailable from: Elliot A Stein
[Show abstract] [Hide abstract]
- "Smoking-induced VST DA release has also been linked to associated behavioral and neurochemical changes in human smokers, including increased hedonic response (Barrett et al., 2004), increased striatal opioid receptor activation (Scott et al., 2007), and improved self-reported mood (Brody et al., 2009b), demonstrating that smoking-related VST DA release correlates with other markers of smoking behavior in humans. The relationship between mood disorders and smoking was further explored in a study that showed that smokers with vs. without a history of major depression had a greater mean decrease in 11 C-raclopride binding potential before to after smoking a cigarette during PET scanning (Brody et al., 2009c). Additional evidence of VST DA signaling abnormalities in smokers was demonstrated in a study of response to challenge with 30 mg of d-amphetamine, where smokers showed blunted VST DA release compared to non-smokers (Busto et al., 2009). "
ABSTRACT: Substantial evidence demonstrates both nicotine's addiction liability and its cognition-enhancing effects. However, the neurobiological mechanisms underlying nicotine's impact on brain function and behavior remain incompletely understood. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation as well as for a number of cognitive disorders such as schizophrenia. Neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), which make it possible to study the actions of nicotine in the human brain in vivo, play an increasingly important role in identifying these dual mechanisms of action. In this review, we summarize the current state of knowledge and discuss outstanding questions and future directions in human neuroimaging research on nicotine and tobacco. This research spans from receptor-level PET and SPECT studies demonstrating nicotine occupancy at nicotinic acetylcholine receptors (nAChRs) and upregulation of nAChRs induced by chronic smoking; through nicotine's interactions with the mesocorticolimbic dopamine system believed to mediate nicotine's reinforcing effects leading to dependence; to functional activity and connectivity fMRI studies documenting nicotine's complex behavioral and cognitive effects manifest by its actions on large-scale brain networks engaged both during task performance and at rest.Neuropharmacology 03/2013; DOI:10.1016/j.neuropharm.2013.02.015 · 4.82 Impact Factor
[Show abstract] [Hide abstract]
- "Converging research supports the notion that depressed adolescents may find smoking more rewarding than nondepressed adolescents. Depression-prone smokers have greater smokinginduced dopamine release than smokers not prone to depression (Brody et al., 2009). It is possible that nicotine's primary reinforcing effects are amplified for youth either prone to depression or during periods of elevated depression symptoms. "
ABSTRACT: While the comorbidity between adolescent depression and smoking has been well documented, less is known about why smoking is disproportionately higher among depressed adolescents. Emerging research suggests that reward-related mechanisms may be important to consider. This study sought to determine whether adolescents with higher depression symptoms have greater smoking reward expectations, which in turn, influence smoking progression. The sample was composed of 1393 adolescents participating in a longitudinal survey study of adolescent health behaviors. In this prospective cohort study, variables were measured via self-report every six months from age 14 to age 17 resulting in six waves of data. Findings Parallel processes latent growth curve modeling indicated that higher depression symptoms across mid to late adolescence predicted a 17% increase in smoking reward expectations (β=3.50, z=2.85, p=0.004), which in turn predicted a 23% increase in the odds of smoking progression (β=0.206, z=3.29, p=0.001). The indirect effect was significant with delta method (β(indirect)=0.72, z=3.09, p=0.002; 95% CI=0.26, 1.18) and bootstrap (β(indirect)=0.72, z=2.10, p=0.03; 95% CI=0.05, 1.39) standard errors. The study provides novel evidence that expectations of smoking reward facilitate smoking uptake among depressed adolescents. Smoking reward expectations may identify depressed adolescents at risk of smoking. Addressing alternative ways to meet the reward expectations rather than smoking may be an important component to consider in the preventing smoking and promoting smoking cessation among adolescents with elevated depression symptoms.Drug and alcohol dependence 08/2011; 120(1-3):181-9. DOI:10.1016/j.drugalcdep.2011.07.020 · 3.28 Impact Factor
[Show abstract] [Hide abstract]
- "Likewise, we are unable to establish if low5-HT 1B receptor binding represents a preexisting vulnerability factor, or rather develops as a consequence of the illness. Lastly, tobacco use was comorbid in our MDD sample (three MDD participants were current smokers vs none in the HC group) and may potentially impact 5-HT 1B signaling by virtue of its influence on striatal DA function (Brody et al. 2009). Our sample size did not allow us to address the influence of smoking status on our findings, and future studies will be needed to clarify the potential role of smokingon5-HT 1B function sufficiently. "
ABSTRACT: Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT(1B) receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT(1B) heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action. The objective of this study was to determine 5-HT(1B) receptor binding potential (BP (ND)) in the region of the ventral striatum/ventral pallidum (VS/VP) in individuals with MDD and healthy control participants. Ten participants with MDD (30.8 ± 9.5 years, five men/five women) in a current major depressive episode (MDE) and ten healthy control participants (30.7 ± 10.5 years, five men/five women) underwent positron emission tomography (PET) scanning with the selective 5-HT(1B) receptor radioligand [(11)C]P943. Within the VS/VP region of interest, [(11)C]P943 BP (ND) was significantly reduced in the MDD group compared with the healthy control group (1.37 ± 0.13 and 1.68 ± 0.16, respectively; 18.7% between-group difference; p < 0.001). Consistent with preclinical and postmortem data, our findings suggest abnormally reduced function of VS/VP 5-HT(1B) receptors in humans with MDD. Abnormal 5-HT(1B) heteroreceptor function may contribute to dysfunctional reward signaling within the striatum, including the nucleus accumbens, via interaction with dopamine, γ-amino-butyric acid, or glutamate systems. Our findings suggest reduced 5-HT(1B) receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT(1B) agonists as a novel class of antidepressants.Psychopharmacology 02/2011; 213(2-3):547-53. DOI:10.1007/s00213-010-1881-0 · 3.99 Impact Factor