Cigarette smoking and progressive brain volume loss in schizophrenia

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Abstract

It is unknown whether the reported brain loss in schizophrenia can be attributed to the effects of tobacco smoking. 96 Patients (54 smokers/42 non-smokers) and 113 control subjects (35/78) were included in a 5-year longitudinal MRI study. Despite the higher prevalence of smoking behavior and the higher number of cigarettes consumed per day in the patients, cigarette smoking did not explain the excessive cerebral (gray matter) volume decreases in the patients. Moreover, smoking was not associated with brain volume change over time in the healthy subjects. However, extremely heavy smoking may contribute to excessive gray matter volume loss in schizophrenia.

Introduction

Despite the well-known health hazards of cigarette smoking its effect on brain morphology has hardly been studied. Cross-sectional brain imaging studies suggest that healthy subjects who smoke cigarettes show smaller gray matter volumes and/or densities in the prefrontal, anterior cingulate, occipital, and temporal cortices (including parahippocampal gyrus), thalamus, substantia nigra and cerebellum as compared to non-smokers (Brody et al., 2004, Gallinat et al., 2006). Moreover, a negative association has been reported between the total number of cigarettes smoked and volume of frontal and temporal lobes and cerebellum (Gallinat et al., 2006). In addition, gray matter density in the bilateral posterior cingulum, precuneus, and frontal cortex, as well as in the right thalamus was found to be decreased in elderly smokers (aged 70–83 years) as compared to similarly aged subjects who had never smoked cigarettes (Almeida et al., 2008).

Patients with a mental illness are about twice as likely to smoke cigarettes as the general population (Lasser et al., 2000) with schizophrenia patients (and patients with substance abuse disorder) displaying the highest prevalence (66% (Poirier et al., 2002)). The overrepresentation of smokers among patients with schizophrenia might be explained by recent implications that the core promoter polymorphisms in the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a susceptibility gene for schizophrenia.(Stephens et al., 2009). Moreover, evidence is accumulating that patients are smoking, at least partially, to self-medicate underlying neuropathology. In a review of the literature it was suggested that sensory processing and cognitive deficits are normalized by smoking in schizophrenia (Leonard et al., 2007).

Since, as indicated, cigarette smoking may be related to smaller brain volumes in healthy subjects and excessive brain loss over time has been convincingly demonstrated in many longitudinal studies in schizophrenia (Hulshoff Pol & Kahn, 2008, Pantelis et al., 2005) the brain volume loss in schizophrenia could be influenced by the (excessive) use of tobacco in these patients. Surprisingly, it has not been studied whether cigarette smoking affects the brain over time, neither in health or disease. This study therefore investigated the effect of cigarette smoking on brain volume change over a 5-year interval in healthy subjects and patients with schizophrenia.

Section snippets

Subjects

Earlier we reported on excessive brain volume loss in patients with schizophrenia relative to control subjects. A total of 96 patients with schizophrenia (54 smokers, 42 non-smokers) and 113 healthy controls (35 smokers, 78 non-smokers) were included in a 5-year longitudinal study (van Haren et al., 2007, van Haren et al., 2008).

Both at baseline and follow-up, psychopathology was assessed using the Comprehensive Assessment of Symptoms and History (CASH (Andreasen et al., 1992)). Diagnostic

Results

A significant overrepresentation of smokers was found in the patient group as compared to the healthy comparison group (χ2 = 13.56, p < 0.001). Moreover, the number of cigarettes smoked per day (at follow-up) in smoking patients (mean [sd] = 23.81 [13.01]) was significantly higher than that in smoking controls (mean [sd] = 10.11 [6.96]); F = 31.65, p < 0.001).

The four groups did not differ with respect to age, level of parental education, gender and handedness distribution. Smoking and non-smoking patients

Discussion

The effect of cigarette smoking on brain volume changes over a five year interval was studied in 96 patients with schizophrenia and 113 healthy subjects. Our main finding is that cigarette smoking does not explain the excessive brain tissue loss over time that we found in the patients relative to the healthy controls, despite a significant overrepresentation of smokers among the patients (56.25%) as compared to the healthy individuals (30.97%). Interestingly, extremely heavy smoking (> 25

Role of the funding source

No funding agency involved.

Contributors

Author NVH designed the study, managed the literature searches and statistical analyses and wrote the first draft of the manuscript. Author PCMPK contributed to the literature searches and statistical analyses of the study. Author WC was responsible for the quality of the clinical data used in this study whereas author HGS developed the imaging software. All authors contributed to and have approved the final manuscript.

Conflict of interest

NVH has received honoraria for education programmes for AstraZeneca, Eli Lilly, Janssen-Cilag. HHP has received honoraria for education programmes for Ferris and Lundbeck. RSK has received grants, honoraria for education programmes, or served as consultant for Astellas, AstraZeneca, BMS, Eli Lilly, Janssen-Cilag, Pfizer, Roche, and Sanofi-Aventis. WC is member of the Advisory Board of Eli Lilly and Janssen-Cilag B.V. She has received honoraria for education programmes for Eli Lilly,

References (21)

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This paper was presented at Human Brain Mapping, June 2008, Melbourne, Australia.

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