Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals: exploring the role of impulsivity, depression, and smoking

Abstract

In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

Keywords: cocaine dependence; depression; drug abuse; frontal; nicotine; voxel-based morphometry.

Figure 1

Mean smaller gray matter volumes observed in 30 non-treatment-seeking cocaine-dependent individuals compared to 33 non-drug using controls in the left middle frontal gyrus using whole-brain voxel-based morphometry analysis. Significant clusters (p < 0.05 corrected, at a height threshold of p < 0.001, uncorrected) are shown on an underlying Montreal Neurological Institute (MNI) template brain (left = left). Statistical tests between groups were performed using ANVOCA covariated for age in SPM8. The red/orange scale represents the corresponding T values.

Figure 2

Visual representation of the correlation between Barratt Impulsivity Scale (BIS) subscores and frontal gray matter volume in non-treatment-seeking cocaine-dependent individuals: positive correlations are shown between (A) BIS attentional impulsivity and right orbitofrontal cortex volume and (B) BIS attentional impulsivity and left precentral gyrus volume, and negative correlations between (C) BIS motor impulsivity and right superior frontal gyrus volume and (D) BIS non-planning impulsivity and right inferior parietal gyrus volume, derived from the model including both BDI and FTND covariates. Left panels: coronal sections illustrating the significant clusters (p < 0.05 corrected, at a height threshold of p < 0.001, uncorrected). Right panels: scatter plots illustrating the correlations in the anatomically defined regions of interest.