Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness

Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness

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J Psychiatry Neurosci 2015;40(3):241-249

Kjetil Nordbø Jørgensen, Cand Psychol*; Ingeborg Skjærvø, MPhil*; Lynn Mørch-Johnsen, MD; Unn Kristin Haukvik, MD, PhD; Elisabeth Heffermehl Lange, MD; Ingrid Melle, MD, PhD; Ole Andreas Andreassen, MD, PhD; Ingrid Agartz, MD, PhD


Background: Magnetic resonance imaging (MRI) studies show reduced cortical thickness in patients with schizophrenia and bipolar disorder. These subtle brain abnormalities may provide insight into illness mechanisms. However, environmental and lifestyle-related factors, such as cigarette smoking, may contribute to brain structure changes. Cigarette smoking is highly prevalent in patients with severe mental illness. In nonpsychiatric samples, smoking has been associated with reduced thickness in the anterior (ACC) and posterior cingulate cortices, the insular cortex (INS), the dorsolateral prefrontal cortex and the orbitofrontal cortex.

Methods: We examined MRI scans from patients with schizophrenia, other psychotic disorders or bipolar disorder and healthy controls using FreeSurfer.

Results: We included 506 patients (49% smokers) and 237 controls (20% smokers) in our study. We found reduced cortical thickness in the left rostral ACC and the left INS in smoking patients compared with nonsmoking patients, but this difference was not found among healthy controls. No dose–response relationship was found between amount of smoking and cortical thickness in these regions. Among patients, maps of thickness along the whole cortical surface revealed reduced insular thickness but no effects in other regions. Among healthy controls, similar analyses revealed increased age-related cortical thinning in the left occipital lobe among smokers compared with nonsmokers.

Limitations: The causal direction could not be determined owing to the cross-sectional design and lack of detailed data on smoking addiction and smoking history.

Conclusion: The effect of cigarette smoking should be considered in MRI studies of patients with severe mental illness.

*These authors contributed equally to this work.

Submitted June 19, 2014; Revised Oct. 7, 2014; Accepted Nov. 28, 2014; Early-released Feb. 10, 2015.

Acknowledgements: The authors thank the study participants and clinicians involved in the recruitment and assessment in the Norwegian Research Center for Mental Disorders (NORMENT) and Stener Nerland for valuable help and advice regarding analyses in FreeSurfer.

Affiliations: From the Department of Psychiatric Research, Diakonhjemmet Hospital, (Jørgensen, Skjærvø, Mørch-Johnsen, Haukvik, Lange, Agartz); NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo ( Jørgensen, Mørch-Johnsen, Haukvik, Lange, Melle, Andreassen, Agartz); the Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo (Skjærvø); and the Division of Mental Health and Addiction, Oslo University Hospital (Melle, Andreassen), Oslo, Norway.

Funding: The study was supported by grants from the Research Council of Norway (grant numbers 190311/V50, 167153/V50, 223273), the South-Eastern Norway Regional Health Authority (grant numbers 2012100, 2011092, 2011096, 2009037) and the K.G. Jebsen Foundation. The funding sources had no further role in the design of the study; in the collection, analysis, and interpretation of the data; in writing the manuscript; or in the decision to submit the paper for publication.

Competing interests: O. Andreassen has received speaker fees from Osaka, GlaxoSmithKline and Lundbeck. No other competing interests declared.

Contributors: K. Jørgensen, I. Skjærvø and I. Agartz designed the study. K. Jørgensen, U. Haukvik, E. Lange, I. Melle, O. Andreassen and I. Agartz acquired the data, which K. Jørgensen, I. Skjærvø, L. Mørch- Johnsen and I. Agartz analyzed. K. Jørgensen and I. Skjærvø wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140163

Correspondence to: K.N. Jørgensen, Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, Vinderen, 0319 OSLO;