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Cytomegalovirus infection associated with smaller cerebellum in severe mental illness

Published online by Cambridge University Press:  19 July 2023

D. Andreou ,
K. N. Jørgensen ,
S. Nerland ,
O. A. Andreassen ,
R. H. Yolken  and
I. Agartz
D. Andreou*
Affiliation:
Department of Psychiatric Research, Diakonhjemmet Hospital Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
K. N. Jørgensen
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Psychiatry, Telemark Hospital, Skien
S. Nerland
Affiliation:
Department of Psychiatric Research, Diakonhjemmet Hospital Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
O. A. Andreassen
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, University of Oslo, Oslo, Norway
R. H. Yolken
Affiliation:
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States
I. Agartz
Affiliation:
Department of Psychiatric Research, Diakonhjemmet Hospital Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
*
*Corresponding author.

Abstract

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Introduction

Postnatal cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent but typically results in lifelong latency. Congenital CMV infections as well as CMV infections in patients with immunodeficiencies have been linked to major cerebellar pathology. Patients with severe mental illness have been repeatedly found to have smaller cerebellum, and they may be particularly susceptible to CMV infections. Finally, both animal and human studies have shown a differential male and female immune response to CMV.

Objectives

We evaluated whole cerebellar grey matter volumes (CGMV) in CMV immunoglobulin G (IgG) seropositive (CMV+) and seronegative (CMV-) patients with severe mental illness and healthy controls (HC). We hypothesized that CMV seropositivity, reflecting previous infection and current latency, is associated with smaller CGMV in patients but not in HC, and that such a putative association may be sex-dependent.

Methods

We included 529 adult patients with severe mental illness (CMV+ 57%, women 48%), i.e., 324 patients with schizophrenia spectrum disorders and 205 patients with bipolar spectrum disorders, and 494 HC (CMV+ 56%, women 45%). MRI scans were obtained with a 1.5T Siemens scanner (n=596) and two 3.0T General Electric scanners (n=427), and processed with FreeSurfer v6.0. Circulating CMV IgG concentrations were measured with immunoassays. In age-, scanner- and estimated total intracranial volume-adjusted analyses of covariance (ANCOVAs), we investigated main and interaction effects of CMV status and sex on CGMV in patients and HC.

Results

CMV+ patients had smaller CGMV than CMV- patients (p=0.042). There was no CGMV difference between CMV+ and CMV- HC (p=0.858). The adjusted CGMV means in CMV+ patients and CMV- patients were 115078 mm3 and 116725 mm3, respectively (p=0.042); the adjusted CGMV means in CMV+ and CMV- HC were 117980 mm3 and 117840 mm3, respectively (p=0.858) (Image). Among patients, a trend towards CMV-by-sex interaction (p=0.073) was found. Post-hoc analyses showed a significant CMV-CGMV association in the female patient group (p=0.005), with no association among male patients (p=0.840).

Image:

Conclusions

CMV IgG seropositivity is associated with smaller cerebellum in severe mental illness, an effect driven by the female patients, but not among HC. This may indicate a CMV-related deleterious impact on cerebellum restricted to patients.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S107
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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