Smoking status as a potential confounder in the study of brain structure in schizophrenia

Abstract

Several but not all MRI studies have reported volume reductions in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. Given the high prevalence of smoking among schizophrenia patients and the fact that smoking has also been associated with alterations in brain morphology, this study evaluated whether a proportion of the known gray matter reductions in key brain regions may be attributed to smoking rather than to schizophrenia alone. We examined structural MRI data of 112 schizophrenia patients (53 smokers and 59 non-smokers) and 77 healthy non-smoker controls collected by the MCIC study of schizophrenia. An automated atlas based probabilistic method was used to generate volumetric measures of the hippocampus and DLPFC. The two patient groups were matched with respect to demographic and clinical variables. Smoker schizophrenia patients showed significantly lower hippocampal and DLPFC volumes than non-smoker schizophrenia patients. Gray matter volume reductions associated with smoking status ranged between 2.2% and 2.8%. Furthermore, we found significant volume differences between smoker patients and healthy controls in the hippocampus and DLPFC, but not between non-smoker patients and healthy controls. Our data suggest that a proportion of the volume reduction seen in the hippocampus and DLPFC in schizophrenia is associated with smoking rather than with the diagnosis of schizophrenia. These results may have important implications for brain imaging studies comparing schizophrenia patients and other groups with a lower smoking prevalence.

Progression from selective to general involvement of hippocampal subfields in schizophrenia

“…Alternatively, this progression could result from an interaction between 1) a fundamental cellular abnormality and 2) environmental factors, 61 including stress, substance use, and/or treatment with antipsychotic medications, all of which have been associated with decreases in brain tissue volume. 67–69 However, when we controlled for antipsychotic medication dosages (as well as the use of mood stabilizers and antidepressants) in the analyses, both our cross-sectional and longitudinal findings in both datasets remained significant, suggesting that progression of atrophy across the hippocampus over time in schizophrenia is not a consequence of medication treatment. Also, it is notable that our longitudinal data were collected in a country (Singapore) with extremely strict prohibitions against (and hence very little) illicit substance use.…”

Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

“…5658 However, findings in patients with schizo phrenia are inconsistent. One ROI study reported smaller grey matter volumes in the hippocampus and the dorsolat eral prefrontal cortex, 58 whereas another study reported larger grey matter volumes in the lateral prefrontal cortex and the superior temporal gyri, 57 and a recent study found no grey matter volume differences between smoking and non smoking patients with schizophrenia. 59 To control for the possible confounding effect of nicotine use, we decided to add nicotine use to the model as a covariate.…”

Neuropsychological profile in adult schizophrenia measured with the CMINDS

“…Based on sex differences reported on the MCCB (Kern et al, 2008), we hypothesized a male advantage on working memory and problem solving and female advantage on verbal learning. Also, given recent evidence for confounding effects of smoking status on structural brain abnormalities (Schneider et al, 2014) as well as cognitive deficits (Hagger-Johnson et al, 2013) and the unresolved issues with regard to medication effects on cognition, we examined the effects of smoking and antipsychotic medication dosing on cognitive performance. Finally, we examined the clinical correlates of global cognitive dysfunction.…”