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

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, VIC 3053, Australia.
Schizophrenia Research (Impact Factor: 3.92). 03/2012; 135(1-3):175-80. DOI: 10.1016/j.schres.2011.11.003
Source: PubMed

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.

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Available from: Luca Cocchi, Sep 28, 2015
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    • "The CUN is believed to have a variety of cognitive functions, including working memory (Bluhm et al. 2011), behavioral engagement (Zhang and Li 2012), monitoring changes of ocular position in response to self-generated eye movements (Law et al. 1998). Actually, Whitford et al. (2012) have suggested that SCZ patients may have abnormalities in monitoring their self-generated eye movements. Our findings of the decreased nodal efficiency in OLF.L in FE-SCZ patients is compatible with a previous study, which suggested the depth of olfactory sulcus may be a static vulnerability marker of SCZ patients (Takahashi et al. 2012). "
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    ABSTRACT: Previous studies suggested that the topological properties of brain anatomical networks may be aberrant in schizophrenia (SCZ), and most of them focused on the chronic and antipsychotic-medicated SCZ patients which may introduce various confounding factors due to antipsychotic medication and duration of illness. To avoid those potential confounders, a desirable approach is to select medication-naïve, first-episode schizophrenia (FE-SCZ) patients. In this study, we acquired diffusion tensor imaging datasets from 30 FE-SCZ patients and 34 age- and gender-matched healthy controls. Taking a distinct gray matter region as a node, inter-regional connectivity as edge and the corresponding streamline counts as edge weight, we constructed whole-brain anatomical networks for both groups, calculated their topological parameters using graph theory, and compared their between-group differences using nonparametric permutation tests. In addition, network-based statistic method was utilized to identify inter-regional connections which were impaired in the FE-SCZ patients. We detected only significantly decreased inter-regional connections in the FE-SCZ patients compared to the controls. These connections were primarily located in the frontal, parietal, occipital, and subcortical regions. Although small-worldness was conserved in the FE-SCZ patients, we found that the network strength and global efficiency as well as the degree were significantly decreased, and shortest path length was significantly increased in the FE-SCZ patients compared to the controls. Most of the regions that showed significantly decreased nodal parameters belonged to the top-down control, sensorimotor, basal ganglia, and limbic-visual system systems. Correlation analysis indicated that the nodal efficiency in the sensorimotor system was negatively correlated with the severity of psychosis symptoms in the FE-SCZ patients. Our results suggest that the network organization is changed in the early stages of the SCZ disease process. Our findings provide useful information for further understanding the brain white matter dysconnectivity of schizophrenia.
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    • "A significant association has been found between high maternal levels of the pro-inflammatory cytokines TNF-α103) and IL-8104) during pregnancy and an increased risk of the progeny developing the clinical features associated with SCZ. Epidemiological evidence suggests immune activation triggered by prenatal exposure to a range of infectious agents, such as herpes simplex virus (HSV-1), cytomegalovirus or influenza, is also associated with a heightened risk of SCZ.33,105-114) Exposure to HSV-1 has been linked to the presence of various structural abnormalities well documented in the brains of patients with SCZ114-116) and in those at high risk of developing psychosis.117) Voxel-based morphometric analyses has revealed that patients with SCZ who tested positive for antibodies to HSV-1 displayed grey matter reductions in the thalamus,115) cerebellum,115) pallidum,115) prefrontal cortex (PFC)118) and anterior cingulate cortex (ACC).114,115) "
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