Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness

Abstract Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the l...

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Main Authors: Dimitrios Andreou, Kjetil Nordbø Jørgensen, Stener Nerland, Torill Ueland, Anja Vaskinn, Unn K. Haukvik, Robert H. Yolken, Ole A. Andreassen, Ingrid Agartz
Format: Article
Language:English
Published: Nature Publishing Group 2022-07-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-022-02044-3
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author Dimitrios Andreou
Kjetil Nordbø Jørgensen
Stener Nerland
Torill Ueland
Anja Vaskinn
Unn K. Haukvik
Robert H. Yolken
Ole A. Andreassen
Ingrid Agartz
author_facet Dimitrios Andreou
Kjetil Nordbø Jørgensen
Stener Nerland
Torill Ueland
Anja Vaskinn
Unn K. Haukvik
Robert H. Yolken
Ole A. Andreassen
Ingrid Agartz
author_sort Dimitrios Andreou
collection DOAJ
description Abstract Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm3 and 654 cm3, respectively; p = 0.019) and lower IQ (104 and 107, respectively; p = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical (p = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.
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spelling doaj.art-730a48e6954145f1837e3605331a8f682022-12-22T03:01:18ZengNature Publishing GroupTranslational Psychiatry2158-31882022-07-011211910.1038/s41398-022-02044-3Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illnessDimitrios Andreou0Kjetil Nordbø Jørgensen1Stener Nerland2Torill Ueland3Anja Vaskinn4Unn K. Haukvik5Robert H. Yolken6Ole A. Andreassen7Ingrid Agartz8Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloPsychosis Research Section, Oslo University HospitalNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of MedicineNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of OsloAbstract Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm3 and 654 cm3, respectively; p = 0.019) and lower IQ (104 and 107, respectively; p = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical (p = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.https://doi.org/10.1038/s41398-022-02044-3
spellingShingle Dimitrios Andreou
Kjetil Nordbø Jørgensen
Stener Nerland
Torill Ueland
Anja Vaskinn
Unn K. Haukvik
Robert H. Yolken
Ole A. Andreassen
Ingrid Agartz
Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
Translational Psychiatry
title Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
title_full Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
title_fullStr Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
title_full_unstemmed Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
title_short Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
title_sort herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness
url https://doi.org/10.1038/s41398-022-02044-3
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