Volumetric Differences of Thalamic Nuclei are Associated with Post-Trauma Psychopathology

Steele, N.; Hussain, A.; Baird, C. L.; Haswell, C. C.; Sun, D.; Rangel-Jimenez, L.; Abdallah, C. G.; Angstadt, M.; August, G.; Berg, H.; Blackford, J. U.; Cisler, J.; Daniels, J. K.; Davenport, N. D.; Davidson, R. J.; Densmore, M.; Disner, S. G.; El-Hage, W.; Etkin, A.; Fani, N.; Frijling, J. L.; Gordon, E. M.; Grupe, D. W.; Herringa, R. J.; Hudson, A. R.; Jahanshad, N.; Jovanovic, T.; King, A.; Koch, S. B. J.; Lanius, R.; Lazarov, A.; Li, G.; Liberzon, I.; Lissek, S.; Lu, G. M.; Manthey, A.; Maron-Katz, A.; Nawijn, L.; Nelson, S. M.; Neria, Y.; Neufeld, R. W. J.; Nitschke, J. B.; Olatunji, B.

doi:10.1101/2025.07.24.666644

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bioRxiv · 10.1101/2025.07.24.666644

Volumetric Differences of Thalamic Nuclei are Associated with Post-Trauma Psychopathology

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Abstract

Previous investigations of whole thalamus and thalamic nuclei volumes in post-trauma psychopathology have been sparse, limited in scope, and yielded inconsistent results. To address this, volumetric estimates of whole thalamus and thalamic nuclei were obtained from structural brain MRI scans from 2,058 participants across 20 worldwide sites in the ENIGMA PTSD working group. Thalamic volumes were compared between trauma-exposed participants with posttraumatic stress disorder (PTSD) (n=238), major depressive disorder (MDD) (n=184), comorbid PTSD+MDD (n=618), and trauma-exposed control participants (n=1,018). PTSD and MDD symptom severity, PTSD symptom clusters, and childhood trauma were similarly examined for associations with thalamic volume. Participants with PTSD only compared to controls had smaller thalamic nuclei volumes in sensorimotor nuclei, including the parafascicular (Pf), ventral anterior magnocellular (VAmc), medial pulvinar (PuM), and anterior pulvinar (PuA) nuclei of the thalamus. MDD only and comorbid PTSD+MDD participants exhibited smaller mediodorsal thalamus volumes compared to controls. Overall PTSD and MDD symptom severity negatively correlated with the volume of the mediodorsal thalamus. A significant interaction between PTSD and MDD severity was found, such that MDD severity was positively associated with thalamic volume only among individuals with high PTSD severity. Avoidance and hyperarousal symptoms of PTSD were positively associated with thalamic volume, while re- experiencing and negative mood/cognition symptoms were negatively associated with thalamic volume. Childhood physical and emotional abuse were positively and negatively associated with thalamic volume, respectively. Whole thalamus volume and volumes of the sensorimotor and limbic thalamus may play an important role in the development of PTSD and MDD in the aftermath of trauma exposure. The interaction between PTSD and MDD symptoms and contrasting effects across PTSD symptom clusters and types of childhood adversity suggests multiple neurobiological mechanisms are involved in shaping thalamic volume post-trauma.

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Steele, N., Hussain, A., Baird, C. L., Haswell, C. C., Sun, D., Rangel-Jimenez, L., Abdallah, C. G., Angstadt, M., August, G., Berg, H., Blackford, J. U., Cisler, J., Daniels, J. K., Davenport, N. D., Davidson, R. J., Densmore, M., Disner, S. G., El-Hage, W., Etkin, A., Fani, N., Frijling, J. L., Gordon, E. M., Grupe, D. W., Herringa, R. J., Hudson, A. R., Jahanshad, N., Jovanovic, T., King, A., Koch, S. B. J., Lanius, R., Lazarov, A., Li, G., Liberzon, I., Lissek, S., Lu, G. M., Manthey, A., Maron-Katz, A., Nawijn, L., Nelson, S. M., Neria, Y., Neufeld, R. W. J., Nitschke, J. B., Olatunji, B.. 2025-07-25. Volumetric Differences of Thalamic Nuclei are Associated with Post-Trauma Psychopathology. https://doi.org/10.1101/2025.07.24.666644

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