2677
Structural MRI at 7T reveals amygdala nuclei and hippocampal subfield volumetric association with Major Depressive Disorder symptom severity1Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Synopsis
Subcortical volumetric changes in MDD have been purported to underlie the symptoms of MDD, however, the evidence to date remains inconsistent. Here, we investigated the relationship between structural limbic brain measurements and MDD symptomology through high-resolution segmentation of the amygdala and hippocampus. We report the novel finding that MDD severity is consistently negatively associated with amygdala nuclei, linking volumetric reductions with worsening depressive symptoms.
Introduction
Major depressive disorder (MDD) is a pervasive and disabling psychiatric illness. Subcortical volumetric changes have been purported to underlie the symptoms of MDD, however, the evidence to date remains inconsistent. Reported volumetric data focused on the hippocampal and amygdala structures in MDD have been notably inconsistent. Larger 1; 2, smaller 3, and no significant differences 4in limbic volumes have all been reported in MDD cohorts compared to control subjects. Heterogeneity within and between sample groups and significant confounding factors have been cited as reasons for disparate findings. To minimize the methodological issues of previous reports, we limited our population to an MDD patient cohort currently not taking antidepressant medication to investigate the association between hippocampal subfield and amygdala nuclei volume and MDD symptom severity. The present study aimed to clarify existing findings of subcortical volumes in major depression by utilizing the enhanced resolution of 7 Tesla (7T) ultra-high field strength MRI.Methods
Structural MRI data was acquired for 24 unmedicated participants with a primary diagnosis of MDD and 20 matched controls on a 7T whole body scanner (Magnetom, Siemens Healthcare, Erlangen, Germany). A SC72CD gradient coil was used with a single coil transmit and a 32-channel head coil (Nova Medical, Wilmington, MA, USA). A T1-weighted MP2RAGE sequence and a coronal-oblique T2-weighted turbo spin echo (T2-TSE) sequence were obtained for all participants.
Image reconstruction and automated segmentation of the whole amygdala into subnuclei and the whole hippocampus into subfields was carried out in FreeSurfer (http://surfer.nmr.mgh.harvard.edu) v6.0. Both T1- and T2-weighted images were utilized to maximize accuracy of the segmentation process. The amygdala was segmented into the lateral, basal, accessory basal, cortical, medial and central nuclei and the corticoamygdaloid transition area (Fig.1). The superficial structures and the deep structures were also investigated as the centrocortical complex (central, medial and cortical nuclei) and the basolateral complex (basal, lateral and accessory basal nuclei) respectively. The hippocampus was segmented into the subiculum, presubiculum, parasubiculum, CA1, CA3, CA4, the granule cell layer of the dentate gyrus, the molecular layer of the dentate gyrus, the hippocampal-amygdala transition area and the fimbria. Subfields were combined into CA1, CA3/4, the subicular complex (pre-, para- and subiculum) and the dentate gyrus (granule cell layer and molecular layer) to ensure subfield structures were large enough for accurate volume quantification (Fig. 2). Additionally, all participants completed the Montgomery-Asberg Depression Rating Scale (MADRS; higher score indicates greater depression severity) to quantify depressive symptomology.
Results
Volumes in the amygdala right lateral nucleus (pFDR= 0.05, r2= 0.24), left cortical nucleus (pFDR= 0.032, r2= 0.35), left accessory basal nucleus (pFDR= 0.04, r2= 0.28) and bilateral corticoamygdaloid transition area (right hemisphere pFDR= 0.032, r2= 0.38, left hemisphere pFDR= 0.032, r2= 0.35) each displayed significant negative associations with MDD severity as measured by the MADRS. When combined into deep and superficial amygdala structures, the bilateral centrocortical (right hemisphere pFDR= 0.032, r2= 0.31, left hemisphere pFDR= 0.032, r2= 0.32) and right basolateral complexes (pFDR= 0.05, r2= 0.24) continued to display significant negative relationships with MDD symptoms (Fig. 3). Regression analyses also revealed associations between MDD severity and volume of the right CA1 subfield and the right CA3/4 subfields, however these did not survive correction for false discovery (pFDR= 0.083, r2= 0.18 and pFDR= 0.062, r2= 0.21 respectively). All analyses were statistically adjusted for age and gender.Discussion
The results reported here concur with a general volumetric sensitivity of amygdala substructures to depression symptom severity as opposed to a vulnerability of specific nuclei. Additionally, our findings suggest a relationship between hippocampal subfields CA1 and CA3/4 and depressive symptom severity at the uncorrected level. It is possible that a combination of diminished neuronal survival promotion and stress-mediated overactivity may lead to a loss of grey matter integrity and volume in the temporal limbic system that is proportionate to symptomatology.Conclusion
Using ultra-high field strength MRI, we report the novel finding that MDD severity is consistently negatively associated with amygdala nuclei, linking volumetric reductions with worsening depressive symptoms.Acknowledgements
NIH RO1 MH109544
NIH R01 CA202911
NARSAD Young Investigator Grant
Icahn School of Medicine Capital Campaign, Translational and Molecular Imaging
Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, Siemens Healthcare
References
1 VAN EIJNDHOVEN, P. et al. Amygdala volume marks the acute state in the early course of depression. Biol Psychiatry, v. 65, n. 9, p. 812-8, May 1 2009. ISSN 1873-2402 (Electronic)0006-3223 (Linking). Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19028381>.
2 FRODL, T. et al. Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Biol Psychiatry, v. 53, n. 4, p. 338-44, Feb 15 2003. ISSN 0006-3223 (Print)0006-3223 (Linking). Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12586453>.
3 TANG, Y. et al. Reduced ventral anterior cingulate and amygdala volumes in medication-naive females with major depressive disorder: A voxel-based morphometric magnetic resonance imaging study. Psychiatry Res,v. 156, n. 1, p. 83-6, Oct 15 2007. ISSN 0165-1781 (Print)0165-1781 (Linking). Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/17825533>.
4 CAMPBELL, S. et al. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry, v. 161, n. 4, p. 598-607, Apr 2004. ISSN 0002-953X (Print)0002-953X (Linking). Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15056502>.
Figures
