The participants were 25 patients (three women) with a diagnosis confirmed with the Structured Clinical Interview for DSM-IV (5) of schizophrenia or schizoaffective disorder. The patients had a mean age of 36.4 years (SD=10.0), an education of 11.7 years (SD=2.0), and an illness duration of 14.0 years (SD=9.5). The participants were inpatients and outpatients recruited from the Rockland Psychiatric Center and Rockland County Department of Mental Health. All of the participants gave written informed consent to participate, and all procedures were approved by local institutional review boards.
The patients completed a neuropsychological test battery from which the following tasks were selected to evaluate three domains derived from a factor analysis (6): verbal declarative memory (N=19) was assessed by using immediate recall for story A from the logical memory subtest of the Wechsler Memory Scale—III (7), attention (N=25) was assessed by using the scaled score for the digit symbol subtest of the WAIS-III, and executive function (N=20) (7) was assessed by using the scaled score from the digit span-backward subtest of the WAIS-III (7).
Scanning was performed on the Nathan Kline Institute’s 1.5-T Siemens Vision System (Erlangen, Germany). Three main sequences were used: magnetization prepared rapidly acquired gradient echo (TR/TE=11.4/4.9 msec, matrix=256×256, field of view=300 mm, number of excitations=1, 1.17-mm slice thickness, 172 slices, no gap), turbo spin echo (TR/TE=5000/22,90 msec, matrix=256×256, field of view=224 mm, number of excitations=1.5-mm slice thickness, 26 slices, no gap), and diffusion tensor imaging (8) (TR/TE=6000/100 msec, matrix=128×128, field of view=240 mm, 5-mm slice thickness, 20 slices, no gap, b=0 s2/mm, number of excitations=2, b=1000 s2/mm, six directions, number of excitations=4).
Diffusion tensor image processing and voxelwise correlational analysis was performed using customized software. The b=0 images were corrected for susceptibility-induced distortion and transformed into Talairach space by using methods described elsewhere (4, 9). The interpolated voxel size was 2×2×2 mm3. A white matter mask was generated by using a nonparametric threshold (10) from the averaged fractional anisotropy map and used to segment the individual images.
The multiple comparisons problem represents a challenge for voxelwise methods; this was reduced by analyzing only white matter. We also selected an approach based on Baudewig et al. (11). We found “seed” voxels using p<0.0005 and then included adjacent voxels with p<0.005, with a minimum cluster volume of 96 mm3. The correlation map was superimposed onto a magnetization prepared rapidly acquired gradient echo image in Talairach space using AFNI (12). Because only white matter was analyzed and, in the absence of a Talairach white matter atlas, some of the specified anatomical regions represent the white matter adjacent to the region named below. Fractional anisotropy was age-adjusted before computation of the correlations. The correlations reported are those for the seed voxel.