1. ¹Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2. ²Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA

Correspondence: Dr KMR Prasad, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. E-mail: PrasadKM@upmc.edu

Received 13 March 2006; Revised 8 August 2006; Accepted 25 August 2006; Published online 10 October 2006.

Abstract

Infectious agents have been proposed as one of the risk factors for schizophrenia. However, the data on the association of infectious agents with in vivo brain changes are scant. We evaluated the association of serological evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain structural variations among first-episode antipsychotic-naive schizophrenia/schizoaffective disorder patients and control subjects. We assayed HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44 healthy subjects and obtained structural magnetic resonance imaging scans from the same individuals. There were proportionately more patients with elevated HSV1 antibody ratios than healthy comparison subjects (²=3.98, 1 df, P=0.046) and patients had significantly higher HSV1 IgG antibody ratios compared with healthy subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1 serological status interaction followed by within- and between-group comparison across the serological status. We observed a diagnosis by HSV1 serological status interaction and a significant main effect of HSV1 serological status in the prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate cortex) compared with patients without serological evidence of exposure to HSV1. HSV1-associated differences in brain structure were not detected among healthy subjects. These findings suggest that HSV1 exposure in schizophrenia is associated with specific regional gray matter differences that may not be attributable to medications, illness chronicity or comorbid substance use. This study provides suggestive evidence for a link between HSV1 exposure and some of the cerebral morphological changes often reported in schizophrenia.