Structural abnormalities in the cuneus associated with Herpes Simplex Virus (type 1) infection in people at ultra high risk of developing psychosis

Thomas J Whitford,Stephen J Wood,Alison Yung,Luca Cocchi,Gregor Berger,Martha E Shenton,Marek Kubicki,Lisa Phillips,Dennis Velakoulis,Robert H Yolken,Christos Pantelis,Patrick Mcgorry,G Paul Amminger

doi:10.1016/j.schres.2011.11.003

Abstract

It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1+), 33 UHR participants without a history of HSV1 exposure (HSV1−) and 19 healthy controls participated in the study. All participants underwent a T1-weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1+ participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1− and healthy control participants (p<0.05, small volume corrected for familywise error). The results of the study suggest that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at ultra-high risk for developing psychosis, and are consistent with previous studies that have identified structural gray matter abnormalities in HSV1-infected patients with established schizophrenia.

Highlights

It has long been suggested that the development of schizophrenia may in some cases be associated with exposure to infectious agents (Crow, 1984; O’Reilly, 1994; Pearce, 2001; Torrey et al, 2006; Yolken et al, 2009; Yolken and Torrey, 1995, 2008)
The present study investigated this question by using voxel-based morphometry to compare the brain structure of people deemed at “ultra-high risk” (UHR) of developing a psychotic disorder, who had a history of Herpes Simplex Virus Type 1 (HSV1) infection, with ultra high risk (UHR) individuals without a history of HSV1 infection, and matched healthy controls
Of the 58 UHR individuals who participated in the study, 25 (43.1%) were classified as being IgG seropositive to HSV1 on the basis of the immunological assay run on their blood sample (HSV1+), while 33 UHR participants (56.9%) were classified as being IgG seronegative (HSV1-)

Summary

Introduction

It has long been suggested that the development of schizophrenia may in some cases be associated with exposure to infectious agents (Crow, 1984; O’Reilly, 1994; Pearce, 2001; Torrey et al, 2006; Yolken et al, 2009; Yolken and Torrey, 1995, 2008). Support for this hypothesis comes from the fact that psychotic individuals are uncommonly likely to have been born during periods of elevated infectious agent activity (Mednick et al, 1988; Torrey et al, 1988), and that babies born in winter, which is the period in which transmissible infections are most likely to occur, are more likely to subsequently develop schizophrenia than babies born in other seasons (Mortensen et al, 1999; Torrey et al, 1997) – see Brown and Derkits (2010) for a review. While the mechanisms of pathogenesis remain a matter of debate, one possibility is that the cycles of latency and reactivation characteristic of HSV1 could cause structural damage to the host cells, which could lead to schizophrenia in predisposed individuals (Pearce, 2001)

Methods

Results

Conclusion