The Association Between Intracortical Myelin and Depression Severity in Mood Disorders
Poster No:
565
Submission Type:
Late-Breaking Abstract Submission
Authors:
Sarah Naseem1, Stefanie Hassel2, Saba Khoshrool3, Christopher Rowley4, Nathan Churchill5, Katharine Dunlop6, Benicio Frey4, Nicholas Bock4
Institutions:
1McMaster University, Hamiliton, Ontario, 2University of Calgary, Calgary , Alberta, 3St. Joseph's Healthcare, Hamilton, Ontario , 4McMaster University, Hamilton, Ontario, 5Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, Toronto, ONTARIO, 6University of Toronto, Toronto, Ontario
First Author:
Co-Author(s):
Nathan Churchill, PhD
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute
Toronto, ONTARIO
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute
Toronto, ONTARIO
Introduction:
Major depressive disorder (MDD) ranks amongst the most prevalent psychiatric disorders worldwide, yet its etiology remains inadequately understood. While emerging evidence from animal (Hu, 2023), human postmortem (Lake, 2017), and preliminary imaging studies (Sacchet, 2017) indicate that intracortical myelination (ICM) disruptions are either associated with the presence of depressive symptoms or an MDD diagnosis, further studies are needed to robustly validate the relationship between ICM disruptions and depressive symptomatology in humans. This study thus investigates the correlation between a quantitative magnetic resonance imaging (qMRI) surrogate marker of ICM, longitudinal relaxation rate (R1), and a measure of depressive symptom severity across the cerebral cortex in a sample of mood disorder patients and healthy controls.
Methods:
The study included 38 participants (11 males, 27 females) aged 19 to 73 years, recruited naturalistically through a master clinical trial platform for mood disorders, comprising of 30 depressive disorders patients, 3 bipolar disorders patients and 5 healthy controls. Depressive symptom severity was evaluated using the 10-item Montgomery–Åsberg Depression Rating Scale (MADRS; Montgomery, 1979). MRIs were collected on a 3T GE system (Discovery 750 version 25.0) using the body coil for transmit and a 32-channel head coil (MR Instruments) for reception. Two 3D gradient-echo images were acquired to generate R1 maps: an inversion-recovery image (Inversion) with 1 mm isotropic resolution optimized to maximize intracortical contrast, and a no-inversion pulse image (No_Inversion) with 1 mm isotropic resolution optimized to minimize intracortical contrast. A B1 transmit field (B1+) map was also collected. The Inversion, No_inversion images and B1+ map were then used to calculate whole-brain R1 maps from look up tables (LUTs) based on numerical simulations of the Bloch equations. Mean ROI R1 values were calculated for each participant across 360 cortical regions as defined by a multi-modal parcellation of the cerebral cortex (Glasser, 2016). The relationship between R1 and depressive symptom severity was modelled using a general linear model: R1 ~ age + age² + sex + MADRS. The model was evaluated using ANCOVAs repeated over ROIs with FDR correction.
Results:
Preliminary analysis revealed no statistically significant associations between R1 and MADRS scores in any ROIs after FDR correction. However, several cortical regions exhibited medium to large partial η² values for the MADRS score term, providing preliminary evidence that R1 and MADRS scores may be related. For example, in the right hemisphere, a large effect size of MADRS score on R1 was observed in the midcingulate cortex (ηp² = 0.15) (Figure 1a). In the left hemisphere, medium to large effect sizes were noted in regions including the anterior cingulate cortex (ηp² = 0.14, Figure 1b), dorsolateral prefrontal cortex (ηp² = 0.16, Figure 2), insular cortex (ηp² = 0.15, Figure 1c) and frontal operculum (ηp²= 0.2, Figure 1d).
Conclusions:
Preliminary findings indicate an association between ICM and depressive symptom severity, offering further evidence that ICM may be disrupted in depression. These results align with existing histopathological and postmortem studies linking ICM abnormalities to depression. Emerging associations in the prefrontal and cingulate cortices are consistent with established research implicating these regions in depression (Fitzgerald, 2008). Data collection is ongoing, with a target sample size of 200 participants. Uncovering ICM disruptions underlying depressive symptomatology seen in depressive disorders could offer key insights into depression's neurobiology and inform targeted myelin-based diagnostics and treatments.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 2
Cortical Cyto- and Myeloarchitecture
Keywords:
Affective Disorders
Cortex
Myelin
STRUCTURAL MRI
Other - Longitudinal Relaxation Rate
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
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Provide references using APA citation style.
Glasser, M. F. (2016). A multi-modal parcellation of human cerebral cortex. Nature, 536(7615), 171-178. https://doi.org/10.1038/nature18933
Hu, Y. Y. (2023). Analysis of the influences of social isolation on cognition and the therapeutic potential of deep brain stimulation in a mouse model. Frontiers in psychiatry, 14, 1186073. https://doi.org/10.3389/fpsyt.2023.1186073
Lake, E. M. (2017). Altered intracortical myelin staining in the dorsolateral prefrontal cortex in severe mental illness. European archives of psychiatry and clinical neuroscience, 267, 369-376. https://doi.org/10.1007/s00406-016-0730-5
Montgomery, S. A. (1979). A new depression scale designed to be sensitive to change. The British journal of psychiatry, 134(4), 382-389. https://doi.org/10.1192/bjp.134.4.382
Sacchet, M. D. (2017). Myelination of the brain in major depressive disorder: an in vivo quantitative magnetic resonance imaging study. Scientific reports, 7(1), 2200. https://doi.org/10.1038/s41598-017-02062-y