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Impaired biophysical integrity of macromolecular protein pools in the uncinate circuit in late-life depression

Molecular Psychiatry volume 24, pages 1844–1855 (2019)Cite this article

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Abstract

Major depressive disorder is a common mood disorder in the elderly. Although the neuroanatomical abnormalities have been identified in patients with late-life depression (LLD), the precise biological basis of LLD remains largely unknown. The purpose of this study was to examine the biophysical integrity of macromolecular protein pools in the nodal regions of the “uncinate circuit,” a component of fronto-limbic circuitry that is connected by the uncinate fasciculus and is critical in the regulation of mood and emotions, using novel magnetization transfer (MT) imaging. Twenty-four patients with LLD and 27 non-depressed healthy control subjects (HCs) of comparable age, sex, and race were recruited from the communities of the greater Chicago Area. The nodal regions of the uncinate circuit, i.e., bilateral amygdala, hippocampus, and lateral and medial orbitofrontal cortices (OFCs), were examined. Compared with HCs, patients with LLD had significantly lower magnetization transfer ratio (MTR), a measure of the biophysical integrity of macromolecular protein pools, in bilateral amygdala and hippocampus. The lower MTR was negatively correlated with the depression score. Moreover, the MTR of these regions decreased with age and positively correlated with neuropsychological performance in the LLD group but not in the HC group. These findings suggest that LLD is associated with compromised biophysical integrity of macromolecular protein pools in nodal regions of the uncinate circuit, and that major depression may accentuate age-related attenuation of the biophysical integrity of macromolecular protein pools in this circuit. These findings provide important new insights into the neurobiological mechanisms of the pathophysiology of LLD.

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Acknowledgements

This work was supported by the NIH grants R01-MH63764 and R01-MH73989. The authors thank Dr. Peter van Zijl and Joseph S. Gillen (Johns Hopkins University) for the MT sequence, which was developed by the support of the National Institute of Biomedical Imaging and Bioengineering resource grant P41 EB015909. Part of data analysis was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health through Grant UL1TR002003. We thank Dr. Dulal K. Bhaumik for very helpful discussion on post hoc power calculation.

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  1. Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Shaolin Yang, Olusola Ajilore, Melissa Lamar & Anand Kumar

  2. Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Shaolin Yang

  3. Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Shaolin Yang

  4. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    Minjie Wu

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Yang, S., Wu, M., Ajilore, O. et al. Impaired biophysical integrity of macromolecular protein pools in the uncinate circuit in late-life depression. Mol Psychiatry 24, 1844–1855 (2019). https://doi.org/10.1038/s41380-018-0085-6

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