Brief reportFamily load impacts orbitofrontal volume in first-episode schizophrenia
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.
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Participants
Participants comprised 23 first episode schizophrenia patients (FE-SZ) who were recruited at the Department of Psychiatry and Psychotherapy, Saarland University, Homburg/Saar, Germany, and 23 healthy controls (HC) matched for age, sex, and handedness. Descriptive data are presented as mean±standard deviation in Supplementary Table 1. In the patient sample, the average duration of untreated psychosis was 46.3 (±62.7) weeks, and the average duration of untreated illness was 184.8 (±168.8) weeks.
Results
Compared with values in the HC group, no significant volumetric differences in the OFC were detected in the FE-SZ group. A comparison of FE-SZ patients with positive family history and those without showed a significant volume decrease of 15% (F=7.8, d.f.=1, 17, p=0.013) in OFC grey matter volume and 21.1% in relative right OFC volume in patients with a genetic load (F=6.4, d.f.=1, 17, p=0.021) (see Fig. 1). Further statistical analyses and results are presented in Supplementary material,
Discussion
The results of this proof-of-concept study indicate an impact of familial load on OFC volumes in FE-SZ patients. We found a significantly decreased right and total OFC volume in FE-SZ patients with a positive family history of schizophrenia compared with those without such a history. However, no significant differences in OFC volumes were detected in the entire FE-SZ group compared with the HC group.
There is some inconsistency in the literature regarding OFC volume differences between
Contributors
T. Wobrock, P. Falkai and O. Gruber developed the study design and enroled patients in the study. W. Reith, A. McIntosh and K. Meyer performed MRI analyses. T. Schneider-Axmann performed the statistical analysis. B. Malchow, K. Radenbach, T. Wobrock, A. Schmitt and A. Hasan were involved in the evaluation of data and preparation of the manuscript.
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