Background Major Depressive Disorder can be seen as a neuropsychological syndrome, associated with morphometric and functional changes in various brain regions, amongst these the anterior cingulate (ACC) and frontal cortex. In addition we found in a previous study a significant correlation between symptom severity and morphometric changes of the insular cortex in participants with Major Depression.1
Aims Using baseline data from the Paddington project WP 2, we wanted to confirm our previous findings and support our hypothesis, that the insula forms an important part of the neural network which underlies depression.
Methods and Results To identify neural structures associated with depression, we used MRI DTI sequences and compared fractional anisotropy (FA)-maps of people with Huntington's disease with low and higher depression scores on the Hamilton scale. Groups were separated by a median split. This resulted in a group of 30 non-depressed participants with a mean depression score of 0.8 (SD 0.7), and a group of 31 mildly depressed participants with a mean depression score of 7.2 (SD 3.5). Imaging data of the non-depressed and the mildly depressed HD group was compared voxel by voxel using t-tests. Statistical results were corrected for multiple comparisons using the false-discovery-rate (FDR) algorithm with a significance level set at p<0.05. We identified seven clusters, which showed reduced FA. These are clusters in the left Insula, left and right cerebellum, the frontal cortex and the ACC. In a second step, we used the identified clusters as regions of interest and correlated individual depression scores with the mean FA of these clusters. Correlations were between r=0.37 and 0.48 (p<0.05, <0.001). In addition, we performed a whole-brain analysis and correlated each voxel with the depression score across all participants. Here we identified the ACC, the insula, and the cerebellum.
Summary of findings We found that FA of the insula cortex and the ACC correlates with severity of depression. This finding emphasises the role of the insula as part of the neuroanatomy of depression. In addition, we found a significant correlation of depression scores with the cerebellum. This finding may be important—there are functional links between the cerebellum and the frontal cortex with respect to cognitive functions (see eg, Canavan et al2). The possibility, that this may also hold true for the emotional/affective domain needs to be explored further.
Funding This work has been supported by the European Union – PADDINGTON project, contract n. HEALTH-F2-2010-261358.
References 1. Sprengelmeyer R, Steele JD, Mwangi B, et al. The insular cortex and the neuroanatomy of major depression. J Affect Disord 2011;133:120–7.
2. Canavan AG, Sprengelmeyer R, Diener HC, et al. Conditional associative learning is impaired in cerebellar disease in humans. Behav Neurosci 1994;108:475–85.
- Diffusion tensor imaging
- multicenter study