Family load impacts orbitofrontal volume in first-episode schizophrenia

Highlights

• MRI volumes of the orbitofrontal cortex (OFC) were measured in first episode schizophrenia versus healthy control subjects.

• The first episode schizophrenia group was subdivided into patients with and without a family history of schizophrenia.

• No significant differences in OFC volumes were found between the total group of first episode schizophrenia patients group and healthy controls.

• The schizophrenia subgroup with a genetic load showed a significant volume decrease in OFC relative grey matter volume.

Abstract

In schizophrenia, reduced orbitofrontal cortex (OFC) volume is inconsistently reported. To investigate the impact of genetic load on OFC volume, manual MRI-tracing in 23 first-episode schizophrenia patients (FE-SZ) and 23 controls was performed. FE-SZ with genetic load showed a decrease in OFC volume compared to FE-SZ without load and controls.

Introduction

Meta-analyses of structural imaging studies bespeak subtle, highly heritable structural brain abnormalities in schizophrenia patients (Wright et al., 2000, Baare et al., 2001, Cannon et al., 2002, Steen et al., 2006). Schizophrenia patients from multiply affected families showed greater impairment in neuropsychological performance than patients with no positive family history of schizophrenia (Sautter et al., 1997). In a magnetic resonance imaging (MRI) study, patients with no family history displayed bilaterally reduced volumes of the temporal lobes, whereas for those with several schizophrenia family members ventricular enlargement has been reported as a marker for genetic liability (McDonald et al., 2002). In a diffusion tensor imaging (DTI) study, patients with a negative family history showed larger deficits in fractional anisotropy (FA) compared with patients with a positive family history (Wang et al., 2011). Increased genetic load likewise was found to be associated with reduced hippocampal volume in schizophrenia (Van Erp et al., 2002).

Brain alterations are present at the onset of disorder (Steen et al., 2006, Vita et al., 2006, Borgwardt et al., 2008, Wood et al., 2008, Witthaus et al., 2009) and seem to progress during the course of the disease compared with findings in healthy controls (Mane et al., 2009). Among other brain regions, inconsistent reductions in volume and cortical thickness of the orbitofrontal cortex (OFC) have been described in antipsychotic-naïve as well as first episode (FE-SZ) patients as well as in chronic schizophrenia patients (Shenton et al., 2001, Antonova et al., 2004, Venkatasubramanian et al., 2008, Schobel et al., 2009, Schultz et al., 2010, Takayanagi et al., 2010). As part of the prefrontal cortex, the OFC with its broad connectivity is critically involved in sensory integration, learning processes and decision-making (Kringelbach, 2005). Following the neurodevelopmental hypothesis of schizophrenia, genetic load may contribute to the reported volume reductions (Schneider-Axmann et al., 2006).

The aim of our study was to for the first time examine the influence of family load on OFC volume in a well-characterised sample of FE-SZ patients with limited exposure to antipsychotic medication. Given the impact of genetic load on the risk to develop schizophrenia, we hypothesised patients with a positive family history of schizophrenia would show the most pronounced volume alterations.