Lifetime cigarette smoking is associated with striatal volume measures

Abstract

Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers' brains have smaller cortical grey matter volumes and/or lower densities compared with non-smokers'. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community-based sample of 'young-old' individuals. Brain volumes were measured using a semi-automated method in 315 participants aged 64-70 years who were selected from a larger randomly sampled cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack-years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.

Striatal Morphology is Associated with Tobacco Cigarette Craving

“…In addition, our novel surface area and shape findings provide more nuanced insight into the relationship between striatal morphology and craving. The relationship between craving and left lateralized striatal volume and surface area is consistent with previous findings linking stimulant abuse with greater left striatal volume (Das et al, 2011;Churchwell et al, 2012, Ersche et al, 2012. The connection between the left striatum and substance abuse may be tied to the more dominant role of the left hemisphere in reward and approach behavior (Davidson and Irwin, 1999).…”

“…For example, enhanced striatal surface area has been associated with obsessive-compulsive disorder (OCD; Shaw et al, 2014), suggesting that larger striatal surface area may be a feature of compulsive disorders including OCD and addiction. Finally, our research focused only on the relationship between striatal morphology and cigarette craving as previous research has shown a clear link between stimulant abuse and enhanced striatal volume when substance abusers and healthy controls were compared (Das et al, 2011;Churchwell et al, 2012, Ersche et al, 2012. It is unclear whether variability in striatal morphology, in non-abusing populations also may explain individual differences in craving severity for other, more natural, reinforcers.…”

“…Recently, larger striatal volume has been linked with greater lifetime exposure to nicotine (Das et al, 2011), which calls into question whether there is a link between striatal function and structural phenotype. Although previous studies have evaluated striatal volume in the context of addiction (Churchwell et al, 2012;Das et al, 2011;Ersche et al, 2012), anomalies in subcortical shape are beginning to emerge as a robust endophenotype in neuropsychiatric disorders , suggesting that this measure may provide additional insight into the relationship between striatal morphology and substance abuse.…”

“…Although both measures evaluate craving, the QSU assesses craving state prior to exposure to smoking cues, whereas cue-induced craving measures the amount of craving induced by visual stimuli associated with nicotine reward. We hypothesize that smokers who report more intense cigarette craving will have larger striatal volume, which may partly explain the connection between larger striatal volume and lifetime cigarette use (Das et al, 2011). In addition, we will build upon the existent literature by providing the first analysis that links cigarette craving and more nuanced measures of striatal morphology including surface area and shape assessments.…”

Assessment of the effect of cigarette smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome

“…Nicotinic acetylcholine receptor (nAChR)s are extensively distributed in the human brain, with the highest density in the thalamus, substantia nigra and cerebral cortex in a decreasing order as well as cerebral vasculature and astrocytes [9,[20][21][22]. Given the associations of brain region and subtype specific attenuations in nAChRs with neuropsychiatric diseases including Alzheimer's and Parkinson's diseases, dementia with Lewy bodies, schizophrenia and autism, studies revealing improvement following nicotine treatment in the animal Parkinsonian models, and larger putamen volumes in individuals with a greater lifetime nicotine exposure, nicotine has been regarded to have a neuroprotective effect [22][23][24]. Either through mesolimbic system activation by nicotine addiction or binding to mostly concentrated nAChRs in the striatum, volume changes in striatum with subsite-dependent alterations have been reported.…”