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Probing midbrain dopamine function in pediatric obsessive-compulsive disorder via neuromelanin-sensitive magnetic resonance imaging

Molecular Psychiatry volume 28, pages 3075–3082 (2023)Cite this article

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Abstract

Obsessive-compulsive disorder (OCD) is an impairing psychiatric condition, which often onsets in childhood. Growing research highlights dopaminergic alterations in adult OCD, yet pediatric studies are limited by methodological constraints. This is the first study to utilize neuromelanin-sensitive MRI as a proxy for dopaminergic function among children with OCD. N = 135 youth (6–14-year-olds) completed high-resolution neuromelanin-sensitive MRI across two sites; n = 64 had an OCD diagnosis. N = 47 children with OCD completed a second scan after cognitive-behavioral therapy. Voxel-wise analyses identified that neuromelanin-MRI signal was higher among children with OCD compared to those without (483 voxels, permutation-corrected p = 0.018). Effects were significant within both the substania nigra pars compacta (p = 0.004, Cohen’s d = 0.51) and ventral tegmental area (p = 0.006, d = 0.50). Follow-up analyses indicated that more severe lifetime symptoms (t = −2.72, p = 0.009) and longer illness duration (t = −2.22, p = 0.03) related to lower neuromelanin-MRI signal. Despite significant symptom reduction with therapy (p < 0.001, d = 1.44), neither baseline nor change in neuromelanin-MRI signal associated with symptom improvement. Current results provide the first demonstration of the utility of neuromelanin-MRI in pediatric psychiatry, specifically highlighting in vivo evidence for midbrain dopamine alterations in treatment-seeking youth with OCD. Neuromelanin-MRI likely indexes accumulating alterations over time, herein, implicating dopamine hyperactivity in OCD. Given evidence of increased neuromelanin signal in pediatric OCD but negative association with symptom severity, additional work is needed to parse potential longitudinal or compensatory mechanisms. Future studies should explore the utility of neuromelanin-MRI biomarkers to identify early risk prior to onset, parse OCD subtypes or symptom heterogeneity, and explore prediction of pharmacotherapy response.

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Fig. 1: Greater neuromelanin-MRI CNR among children with OCD.
Fig. 2: Group differences and symptom assocaitions with neuromelanin-MRI CNR.

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Acknowledgements

This work was partially supported by funds from the National Institute of Mental Health (R01 MH115024, PIs: Marsh & Fitzgerald) as was the efforts of the authors: Dr. Pagliaccio (R21 MH125044, R01 MH126181), Dr. Horga (R01 MH117323, R01 MH114965), Dr. Wengler (F32 MH125540). Preliminary findings from this work were presented at the 2021 meeting of the Society for Biological Psychiatry (https://doi.org/10.1016/j.biopsych.2021.02.212). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Pagliaccio confirms that he had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA

    David Pagliaccio, Kenneth Wengler, Katherine Durham, Martine Fontaine, Meryl Rueppel, Sarah Pieper, Caroline Risdon, Guillermo Horga, Kate D. Fitzgerald & Rachel Marsh

  2. New York State Psychiatric Institute, New York, NY, USA

    David Pagliaccio, Kenneth Wengler, Katherine Durham, Martine Fontaine, Meryl Rueppel, Sarah Pieper, Caroline Risdon, Guillermo Horga, Kate D. Fitzgerald & Rachel Marsh

  3. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

    Hannah Becker & Emily Bilek

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Contributions

DP analyzed study data and prepared the manuscript. KW and GH developed the neuromelanin-MRI protocol and processing pipeline. MF oversaw MRI data collection and quality control. KD, HB, and EB conducted and oversaw clinical assessment procedures. MR, SP, and CR collected study data and performed data quality control. DP, KDF, and RM designed the study and oversaw study procedures. All authors contributed to manuscript review and editing.

Corresponding author

Correspondence to David Pagliaccio.

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Competing interests

KW and GH report having filed patents for analysis and use of neuromelanin imaging in central nervous system disorders, licensed to Terran Biosciences, but have received no royalties. All other authors reported no biomedical financial interests or potential conflicts of interest.

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Pagliaccio, D., Wengler, K., Durham, K. et al. Probing midbrain dopamine function in pediatric obsessive-compulsive disorder via neuromelanin-sensitive magnetic resonance imaging. Mol Psychiatry 28, 3075–3082 (2023). https://doi.org/10.1038/s41380-023-02105-z

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