Introduction Friston and Frith, 1995 Catani and ffytche, 2005 Shenton et al., 2001; Bagary et al., 2003; Foong et al., 2001 Harrison and Weinberger, 2005 Walterfang et al., 2006 Pujol et al., 1993 Crow (1998) Shenton et al., 2001 Keshavan et al., 2002 Goghari et al., 2005 Bachmann et al. (2003) Keller et al., 2003 Hulshoff Pol et al., 2004 Foong et al., 2001 Highley et al. (1999a) Innocenti et al., 2003 Basser et al., 1994 Foong et al., 2000 Agartz et al., 2001 Brambilla et al., 2005; Ardekani et al., 2003; Kubicki et al., 2005 Kumra et al. (2004) Price et al., 2005 Brambilla et al. (2005) Mori et al., 1999 Toosy et al., 2004; Parker and Alexander, 2005; Parker et al., 2005 Wilson et al., 2003 Lee et al., 2004 Huang et al., 2005 Kanaan et al., 2006 Here we present, to our knowledge, the first study of the corpus callosum (or indeed any white matter pathway) in patients with first-episode schizophrenia spectrum disorders using diffusion imaging tractography. The main aim of the study was to determine whether subtle abnormalities of interhemispheric connections could be detected using this new technique in a group of patients during the first-episode of psychosis, in whom chronicity-related factors could be excluded. We hypothesized that measures of tract coherence (FA), in white matter traversing the genu and splenium of the corpus callosum, would be significantly reduced in the patient group compared to controls. Materials and methods Jablensky et al., 1992 Jablensky et al., 2000 McGuffin et al., 1991 Wing et al., 1990 http://sgdp.iop.kcl.ac.uk/opcrit/ Eighteen patients with an initial diagnosis of schizophrenia, schizophreniform or schizoaffective disorder took part in this study. Fifteen of these patients were interviewed again a year later to review the diagnosis, and for the remaining three, who could not be interviewed, a final diagnosis was established also a year later by compiling information from clinicians looking after the patients and by reviewing the clinical notes. Thirteen patients received a final diagnosis of schizophrenia and the remaining five received a diagnosis of schizoaffective disorder (one bipolar, two manic and two depressed subtype). The patients had been ill for a mean of 12.6 months (SD = 19.3 months, range 0–72 months) at entry into the study. Andreasen, 1983 Andreasen, 1981 Young et al., 1978 Hamilton, 1960 Perkins et al., 2000 Drake et al., 1990 Annett, 1970 Westerhausen et al., 2003 Table 1 MRI data acquisition 1 2 2 2 2 2 Δ δ b 2 b 2 Diffusion processing and analysis Basser et al. (1994) Alexander et al., 2002 Parker and Alexander (2003) Parker and Alexander, 2003, 2005 Parker and Alexander, 2005 Behrens et al. (2003) http://www.sph.sc.edu/comd/rorden/ The seed region placement was the only operator-dependent step in the diffusion processing. To assess the inter-rater reliability of the method, a second, independent rater performed the seed region placement in 8 cases, using the same procedure. Toosy et al., 2004 Toosy et al., 2004; Parker et al., 2005 b Good et al. (2001) Ashburner and Friston, 2000 3 Statistical analysis t χ 2 σ μ σ μ Zellner, 1962 F F A voxel-based statistical comparison between CSF maps from patients and controls was performed in SPM2 based on the General Linear Model and Gaussian random field theory incorporating subject age and gender into this model. Results t df P χ 2 df P χ 2 df P Table 1 The coefficient of variation for the tract volume for the 8 repeated measurements performed by two raters was 1.36%, indicating a very high inter-rater reproducibility. Figs. 1 and 2 Figs. 3 Table 2 P Table 2 P P P P P f 3 3 t P Discussion Our findings provide evidence of altered interhemispheric connectivity in patients with first-episode schizophrenia spectrum disorders. In the patient group, abnormal tract coherence, as measured by reduction in FA, was present in tracts traversing the genu and, to a lesser extent, in those traversing the splenium. Tract coherence, as measured by FA, was lower in females, both in patients and controls, but we failed to find a gender-by-group interaction. Innocenti et al., 2003 Walterfang et al., 2006 Kanaan et al., 2006 Zellner, 1962 Jones et al., 2005 Price et al., 2005; Jones et al., 2005 Flynn et al., 2003 Price et al., 2005 Westerhausen et al. (2003) Dubb et al. (2003) Beaulieu, 2002 Bachmann et al. (2003) Brambilla et al., 2003, 2004 Szeszko et al., 2005 Adler et al., 2006 Tkachev et al., 2003; Iwamoto et al., 2005 Highley et al. (1999b) Kubicki et al., 2005 Agartz et al., 2006 Price et al., 2005; Kanaan et al., 2006