Reduced olfactory bulb volume in depression-A structural moderator analysis

Abstract

Background: Removal of the olfactory bulb (OB) leads to depression like behavior in rodents. A link between depression and olfactory function is also established in humans. We hypothesized that the human OB volume relates to depressive state and tested whether such a potential coherence is moderated by structural alterations in other brain regions.

Methods: Eighty-three participants (32 patients with major depression and 51 matched healthy controls) underwent structural MR scanning. Individual OB volumes were compared between patients and controls and the impact of depression and comorbidity was analyzed with multiple regression analysis. Whole-brain voxel-based morphometry revealed structures co-varying with both depressive state and OB volume.

Results: The OB volume of patients was significantly reduced and this reduction averaged out at 17% compared to the controls. The OB volume was correlated to the volume of the insula, superior temporal cortex, and amygdala. The independent variables of depression (β = -.37), age (β = -.25), and gender (β = -.40) explained the individual OB volume variation (R² = .37). The correlation between OB volume and depression was moderated by volumetric reductions in a cluster including the insula and superior temporal gyrus (STG).

Conclusions: The OB volume relates to depression in humans and to the volume of structures which are critical for salience detection. We assume that a reduced OB volume causes diminished neural olfactory input which facilitates volume reduction in the insula and STG. The OB volume may hence constitute a factor of vulnerability to depression. Olfactory-based deep brain stimulation is discussed as a future therapeutic approach.

Keywords: amygdala; gray matter volume; insula; salience; superior temporal gyrus.

Figure 1

Picture displaying the position of the OB (encircled in yellow) in the human brain [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Diagram showing the olfactory bulb volumes of each individual of the patient and healthy control group. Olfactory bulb volumes are displayed in mm³. Means of OB volumes for each group are shown in the boxes

Figure 3

Brain maps showing positive association between gray matter volume and olfactory bulb volume (upper panel), areas with reduced GM volume in depression (mid panel), and the positive association between gray matter volume and OB volume after inclusive masking for areas that are reduced in depression (lower panel). All brain maps are thresholded at p < .001 with a non‐stationary cluster‐extent‐based threshold of k > 139 voxels which was calculated with VBM‐8 toolbox for SPM (http://dbm.neuro.uni-jena.de/vbm). The data are visualized on a template provided by MRIcron (http://www.nitrc.org/projects/mricron) [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Association between OB volume and severity of depression (BDI score) was moderated by the GM volume in the left STG/insula. Path a illustrates the association between OB volume and GM volume in the left STG/insula; Path b indicates the association between depression severity (BDI score) and GM volume in the left STG/insula; Path c illustrates the indirect association between OB volume and depression score (BDI) (in black); Path c′ illustrates the direct association between OB volume and depression severity (BDI score) after controlling for GM volume of the left STG/insula (in red). Correlations and levels of significance are shown next to arrows. All analyses were controlled for TIV