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

Abstract

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.

Fig. 1

Cortical map showing the selected parcellated regions based on the Desikan–Killiany atlas. Regions in the cingulum (anterior cingulate cortex, posterior cingulate cortex) are shown in green. Regions in the orbitofrontal cortex are shown in red. The insula is shown in blue and the dorsolateral prefrontal cortex is shown in yellow.

Fig. 2

The top statistical map illustrates differences in cortical thickness between smoking and nonsmoking patients. The blue area indicates a significantly thinner cortex (p < 0.05, false-discovery rate [FDR]–corrected) in smokers compared with nonsmokers. Since no areas were significantly different in the right hemisphere and no differences emerged in the medial view, only the lateral view of the left hemisphere is provided. The 2 bottom statistical maps illustrate different age slopes between smoking and nonsmoking healthy controls. Blue areas indicate a steeper slope, with increased thinning with older age among smokers (p < 0.05, FDR-corrected). All analyses were adjusted for age, sex and diagnosis (patients only) and were performed in FreeSurfer using the general linear model function.