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Published Online: 5 June 2019

Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum

Paulo Lizano, M.D., Ph.D. [email protected], Olivia Lutz, B.S., George Ling, M.S., Adam M. Lee, Ph.D., Seenae Eum, Pharm.D., Jeffrey R. Bishop, Pharm.D., Sinead Kelly, Ph.D., Ofer Pasternak, Ph.D., Brett Clementz, Ph.D., Godfrey Pearlson, M.D., John A. Sweeney, Ph.D., Elliot Gershon, M.D., Carol Tamminga, M.D., and Matcheri Keshavan, M.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 176, Number 7
https://doi.org/10.1176/appi.ajp.2019.18070825
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Abstract

Objective:

The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures.

Methods:

Choroid plexus volume was quantified (using FreeSurfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects.

Results:

Choroid plexus volume was significantly larger in probands compared with first-degree relatives or healthy control subjects; first-degree relatives had intermediate enlargement compared with healthy control subjects; and total choroid plexus volume was significantly heritable. Larger volume was associated with worse cognition, smaller total gray matter and amygdala volume, larger lateral ventricle volume, and lower structural connectivity in probands. Associations between larger volume and higher levels of interleukin 6 in probands was also observed.

Conclusions:

These findings suggest the involvement of the choroid plexus across the psychosis spectrum with a potential pathophysiological mechanism involving the neuroimmune axis, which functions in maintaining brain homeostasis and interacting with the peripheral immune and inflammatory system. The choroid plexus may be an important target in future research.

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Supplementary Material

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 176 • Number 7 • July 01, 2019
Pages: 564 - 572
PubMed: 31164007

History

Received: 14 July 2018
Revision received: 4 January 2019
Accepted: 25 February 2019
Published online: 5 June 2019
Published in print: July 01, 2019

Keywords

  1. Choroid Plexus
  2. Psychosis

Authors

Affiliations

Paulo Lizano, M.D., Ph.D. [email protected]
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Olivia Lutz, B.S.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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George Ling, M.S.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Adam M. Lee, Ph.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Seenae Eum, Pharm.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Jeffrey R. Bishop, Pharm.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Sinead Kelly, Ph.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Ofer Pasternak, Ph.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Brett Clementz, Ph.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Godfrey Pearlson, M.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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John A. Sweeney, Ph.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Elliot Gershon, M.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Carol Tamminga, M.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Matcheri Keshavan, M.D.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston (Lizano, Lutz, Ling, Kelly, Keshavan); the Department of Psychiatry, Harvard Medical School, Boston (Lizano, Kelly, Pasternak, Keshavan); the University of Minnesota Academic Health Center, Minneapolis (Lee, Eum, Bishop); the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens (Clementz); the Olin Neuropsychiatry Research Center/Institute of Living, Hartford Hospital, Hartford, Conn. (Pearlson); the Department of Psychiatry, University of Cincinnati (Sweeney); the Department of Psychiatry, University of Chicago (Gershon); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Tamminga).
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Notes

Send correspondence to Dr. Lizano ([email protected]).
Previously presented at the 29th annual meeting of the American Neuropsychiatric Association, Boston, March 21–24, 2018.

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

Harvard Medical Schoolhttp://dx.doi.org/10.13039/100006691: Livingston grant (Dr. Lizano)
National Center for Advancing Translational Sciences of the National Institutes of Health Award: UL1TR000114 (Dr. Bishop)
National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: MH-077851 (Dr. Tamminga), MH-078113 (Dr. Keshavan)
Commonwealth Research Center: SCDMH82101008006 (Dr. Keshavan)
Supported in part by NIMH grants MH-077851 (to Dr. Tamminga), MH-078113 (to Dr. Keshavan), MH-077945 (to Dr. Pearlson), MH-077852 (to Dr. Thaker), and MH-077862 (to Dr. Sweeney); the Commonwealth Research Center (grant SCDMH82101008006 to Dr. Keshavan); the NIH’s National Center for Advancing Translational Sciences (grant UL1TR000114 to Dr. Bishop); and a Livingston Award from Harvard Medical School (to Dr. Lizano).

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