Insomnia is Negatively Associated with Frontolimbic Intracortical Myelin in Major Depressive Disorde

Poster No:

523 

Submission Type:

Abstract Submission 

Authors:

Kristian Jensen1, Anders Spanggård1, Jonas Kendal1, Melanie Ganz1, Kristin Köhler-Forsberg1, Gitte Knudsen1, Vibe Frokjaer1, Martin Jørgensen2

Institutions:

1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 2Psychiatric Center Copenhagen, Copenhagen, Denmark

First Author:

Kristian Jensen  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark

Co-Author(s):

Anders Spanggård  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Jonas Kendal  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Melanie Ganz  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Kristin Köhler-Forsberg  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Gitte Knudsen  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Vibe Frokjaer  
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Martin Jørgensen  
Psychiatric Center Copenhagen
Copenhagen, Denmark

Introduction:

Reduced intracortical myelin (i.e. myelin in the grey matter) has been observed in frontolimbic regions in patients with major depressive disorder (MDD) (Baranger et al. 2021, Zhang et al. 2023, Sacchet and Gotlib 2017), but its relationship with specific symptoms remains unclear. Evidence suggests sleep disruption may impact brain myelination (Toschi et al. 2020), yet the association between intracortical myelin and insomnia in MDD has yet to be investigated.

Methods:

We estimated intracortical myelin using T1/T2-weighted MRI ratios (3 Tesla Siemens Prisma) in 96 unmedicated MDD patients (72% female, 18-60 years old) (Köhler-Forsberg et al. 2020). The T1/T2-ratio was calculated using FreeSurfer v.7.2 after alignment and quality control (excluding voxel values of 0 and >100 to remove CSF and small vessels) as Glasser et al 2011. Regions of interest were parcellated using the Desikan-Killiany-Tourville atlas, and an average T1-/T2-ratio was calculated for all voxels in each region. Intracortical myelin was assessed in the prefrontal cortex, anterior cingulate cortex, and insula. Depression severity was measured using the 17-item Hamilton Depression Rating Scale, with a specific analysis of insomnia. Analyses were adjusted for age and sex and multiple comparisons using Benjamini-Hochberg correction.

Results:

Greater depression severity was associated with reduced intracortical myelin in the right superior prefrontal cortex and right insula (p-values=0.038). Notably, exploratory analysis revealed that this association was primarily driven by delayed sleep initiation and early morning insomnia (Hamilton items 4-6). Other symptoms contributing to this relationship included somatic anxiety and suicidal ideation, both of which have previously been linked to sleep disturbance (Liu et al. 2006).

Conclusions:

Our findings suggest that insomnia in MDD is associated with reduced frontolimbic intracortical myelin. This aligns with research showing that poor sleep quality correlates with reduced intracortical myelin (Toschi et al. 2020), and chronic sleep deprivation can reduce myelin thickness in animal models (Bellesi et al. 2018). These results highlight the importance of addressing sleep disturbances in MDD and suggest that intracortical myelin alterations might represent a neurobiological marker of insomnia in depression.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Cyto- and Myeloarchitecture 2

Perception, Attention and Motor Behavior:

Sleep and Wakefulness

Keywords:

Myelin
Psychiatric Disorders
Sleep
STRUCTURAL MRI

1|2Indicates the priority used for review

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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.

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Provide references using APA citation style.

Baranger, D. A. A., Halchenko, Y. O., Satz, S., Ragozzino, R., Iyengar, S., Swartz, H. A., et al. (2021). Aberrant levels of cortical myelin distinguish individuals with depressive disorders from healthy controls. NeuroImage: Clinical, 32, 102790. https://doi.org/10.1016/j.nicl.2021.102790

Bellesi, M., Haswell, J. D., De Vivo, L., Marshall, W., Roseboom, P. H., Tononi, G., et al. (2018). Myelin modifications after chronic sleep loss in adolescent mice. Sleep, 41(6), zsy034. https://doi.org/10.1093/sleep/zsy034

Glasser, M. F., & Van Essen, D. C. (2011). Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI. Journal of Neuroscience, 31(32), 11597–11616. https://doi.org/10.1523/JNEUROSCI.2180-11.2011

Liu, X., & Buysse, D. J. (2006). Sleep and youth suicidal behaviour: A neglected field. Current Opinion in Psychiatry, 19(3), 288–293. https://doi.org/10.1097/01.yco.0000218593.32229.59

Köhler-Forsberg, K., Jorgensen, A., Dam, V. H., Stenbæk, D. S., Fisher, P. M., Ip, C.-T., Ganz, M., Poulsen, H. E., Giraldi, A., Ozenne, B., Jørgensen, M. B., Knudsen, G. M., & Frokjaer, V. G. (2020). Predicting treatment outcome in major depressive disorder using serotonin 4 receptor PET brain imaging, functional MRI, cognitive-, EEG-based, and peripheral biomarkers: A NeuroPharm open label clinical trial protocol. Frontiers in Psychiatry, 11, 641. https://doi.org/10.3389/fpsyt.2020.00641

Sacchet, M. D., & Gotlib, I. H. (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

Toschi, N., Passamonti, L., & Bellesi, M. (2020). Sleep quality relates to emotional reactivity via intracortical myelination. Sleep, 44(1), zsaa146. https://doi.org/10.1093/sleep/zsaa146

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