Meta-analysis of magnetic resonance imaging studies of the corpus callosum in schizophrenia

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Abstract

Objectives

The corpus callosum plays a pivotal role in inter-hemispheric transfer and integration of information. Magnetic resonance studies have reported callosal abnormalities in schizophrenia but findings have been inconsistent. Uncertainty has persisted despite a meta-analytic evaluation of this structure several years ago. We set out to perform a further meta-analysis with the addition of the numerous reports published on the subject to test the hypothesis that the corpus callosum is abnormal in schizophrenia.

Method

A systematic search was carried out to identify suitable magnetic resonance studies which reported callosal areas in schizophrenia compared to controls. Results from the retrieved studies were compared in a meta-analysis whilst the influence of biological and clinical variables on effect size was ascertained with meta-regression analysis.

Results

Twenty-eight studies were identified. Corpus callosum area was reduced in schizophrenia in comparison to healthy volunteers. This effect was larger in first episode patients. Similarly, heterogeneity detected among the studies was associated with course of illness indicating that chronic subjects with schizophrenia showed larger callosal areas. There was no evidence of publication bias.

Conclusions

This study confirms the presence of reduced callosal areas in schizophrenia. The effect is of a larger magnitude at first presentation and less so in subjects with a chronic course generally medicated with antipsychotics.

Introduction

The corpus callosum (CC) has long been a structure of interest in the study of schizophrenia. This interest originates from a number of observations: i) the well established anatomical significance of the CC in relaying sensory, motor and cognitive information from homologous brain regions (De Lacoste et al., 1985, Pandya and Seltzer, 1986), ii) evidence of impaired callosal transfer in schizophrenia (David, 1994), and iii) the observation of anatomical dys-morphology in post mortem studies either expressed as increased/decreased thickness, decreased cross-sectional area or decreased fibre density in schizophrenia (e.g. Rosenthal and Bigelow, 1972, Bigelow et al., 1983, Highley et al., 1999). From the mid 90′s magnetic resonance imaging (MRI) has been applied to examine the cross-sectional area of the CC in the mid-sagittal-plane in schizophrenia. Results across the studies have not always been concordant in their findings. Some studies have indicated a reduction in callosal areas whereas some others haven't reported statistically significant differences. Some studies which considered gender differences and callosal areas have indicated a decrease in CC areas in schizophrenic males but not females or vice versa. Findings from these studies suggest a small variability of the size of the CC in schizophrenia compared to normal controls susceptible to the influence of a number of biological variables (e.g. age, gender and inter-individual variability) and clinical variables. Such confounders are likely to be influenced by sample selection in individual studies, methodology adopted and neuroimaging techniques used. Meta-analysis as a technique can combine quantitative data from individual studies, increasing power to detect subtle anatomical differences and investigate causes of heterogeneity (Hunter and Schmidt, 1990, Thompson et al., 1997, Wright et al., 2000). A previous meta-analysis of mid-sagittal callosal areas in schizophrenia (Woodruff et al., 1995) incorporating findings of eleven structural imaging studies found that schizophrenic patients have a small but significant reduction of CC area. We set out to investigate corpus callosum mid-sagittal area in schizophrenia by performing a meta-analysis with the addition of the numerous reports published since 1995. The aims of this meta-analysis were (1) to establish whether current knowledge of callosal abnormalities in schizophrenia are confirmed by including further published reports, (2) to investigate the effect on callosal areas exercised by the course of illness (e.g. acute versus chronic course), and (3) to assess heterogeneity by clarifying the role of biological variables (e.g. age, gender) and illness variables (e.g., age of onset, duration of illness, severity of symptoms, duration of untreated psychosis), and year of publication (as expression methodological differences across the studies).

Section snippets

Search strategy and inclusion/exclusion criteria

A comprehensive search from a range of electronic databases, including The Cochrane Library, EMBASE, PsycINFO, and PubMED was conducted up to May 2007. Key words used to identify the studies were: magnetic resonance imaging, MRI, corpus callosum, schizophrenia, corpus callosum and schizophrenia, magnetic resonance imaging and schizophrenia, MRI and schizophrenia. The search was also complemented by a manual and bibliographic cross-referencing. Studies were included if they presented original

Systematic search

Forty-nine reports were identified comparing schizophrenic patients with healthy unrelated controls. Twenty-eight studies met inclusion criteria and are described in detail in Table 1. Only four of these studies included a minority of schizotypal, schizophreniform, or schizoaffective patients (Hoff et al., 1994, Hendren et al., 1995, Keshavan et al., 2002, Bachmann et al., 2003). Four of these studies were included after authors were contacted to complement information published (Hendren et

Discussion

This study highlights the great interest among researchers in investigating structural callosal changes in schizophrenia. In agreement with Woodruff et al. (1995), we have demonstrated that compared to controls, CC area is significantly reduced in patients with schizophrenia. We also found that this effect is maximised at first presentation and is less prominent when the illness assumes a chronic course.

We investigated the heterogeneity with meta-regression techniques. In our analysis, the

Role of funding source

No funding source involved.

Contributors

DA was involved in literature searches, data extraction and analyses, and in writing the first draft of the report. GMYT had a role in data extraction. AMM provided supervision, statistical expertise, offered guidance in the interpretation of the results and participated at all stages of development of the final report. KPE had a role in overall supervision and final drafting of the report. All the authors contributed to and have approved the final manuscript.

Conflict of interest

Nothing to declare.

Acknowledgments

DA would like to thank Dr Ellison-Wright for conceiving the idea of this project and motivating him to pursue this area of research.

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