MD and CSF measures obtained from the entire brain (Pearson's r = .80, df = 113, P < 0.0001) and for each region of interest (r: .39-.82, df = 113, P < 0.0001) were highly correlated. Whole brain MD and gray matter volumes also showed significant relationships (r = -.44, df = 113, P < 0.0001), though to a lesser degree. Relationships between MD and white matter volumes were not significant (r = -.01, df = 113, P > 0.10). The relationships of whole brain MD with each brain tissue compartment are plotted in .
The relationship between MD and each tissue compartment (CSF, white matter and gray matter) for the entire brain are shown across all groups (N = 114).
Schizophrenia probands exhibited significantly larger MD indices within the left, F(1, 45) = 8.02, P < 0.007, and right temporal lobe, F(1,45) = 11.73, P < 0.001, and within the left, F(1,45) = 12.31, P < 0.001, and right, F(1,45) = 19.32, P < 0.0001, superior temporal gyrus, compared to unrelated control probands. Effects in the same regions were pronounced after covarying for CSF volume, (F(1,44) = 14. 89; F(1,44) = 22.39; F(1,44) = 25.17; F(1,44) = 28.58, all P < 0.0001, for left and right temporal, and superior temporal gyrus regions respectively).
First-degree relatives from families with a schizophrenia proband showed increased MD with respect to control subjects and relatives in the left and right superior temporal gyrus after covarying for CSF volume, F(1,84) = 7.05 and F(1,84) = 5.90 respectively, both P < 0.01. These effects were at trend level significance without covarying for CSF (P < 0.10). Genetic liability findings were similar when control relatives and patient relatives were compared without including control probands in the analysis. That is, patient relatives showed larger MD indices in the left (F(1,64) = 4.14, P < 0.05) and marginally in the right (F(1,64) = 3.86, P < 0.054) superior temporal gyrus with CSF volume correction compared to control relatives. Significant schizophrenia and genetic liability effects for MD were absent for the other ROIs examined. shows the 95% confidence intervals of the means for sex and age-regressed superior temporal gyrus MD within control probands and relatives, relatives of schizophrenia patients and schizophrenia probands with and without CSF volume correction.
Figure 3 Means and 95% confidence intervals for left and right superior temporal gyrus MD within control probands and relatives (n = 52), patient relatives (n = 36) and schizophrenia probands (n = 26). Results are shown after adjusting the data for sex and age (more ...)
For examination of regional CSF volumes, schizophrenia probands showed greater CSF within superior temporal gyrus regions bilaterally (left: (F(1,44) = 12.59; right: F(1,44) = 4.70, P < 0.03) after correction for overall CSF volume, and within left superior temporal gyrus regions F(1,45) = 5.53, P < 0.02 without correction. Significant schizophrenia liability effects were observed for the left superior temporal gyrus after covarying for global CSF volume, F(1,83) = 6.70, P < 0.01. Means and standard deviations for sex and age-adjusted MD and CSF volume measures are provided in within groups defined by disease status and family membership.
Means and Standard Deviations (SD) for sex and age-adjusted regional MD (mm2/s) and CSF volume (cm3) measures.
Finally, post-hoc analyses of gray matter volumes within the superior temporal gyrus showed significant schizophrenia effects for the right hemisphere, F(1, 44) = 4.22, P < 0.04 after correction for overall gray matter volume (age and sex-adjusted mean ± SD for schizophrenia probands: 18.44 ± 1.72 cm3 and control probands: 18.76 ± 2.19 cm3), but not in the left hemisphere, P>0.05 (mean ± SD for schizophrenia probands: 19.95 ± 2.10 cm3 and control probands: 19.91 ± 2.30 cm3). Relatives of patients with schizophrenia failed to exhibit significant differences in superior temporal gyrus gray matter volumes compared to healthy subjects, P > 0.10. shows the means and 95% confidence intervals for sex and age-regressed superior temporal gyrus CSF and gray matter volumes within control probands and relatives, relatives of schizophrenia patients and schizophrenia probands.
Figure 4 Means and 95% confidence intervals for left and right superior temporal gyrus CSF (top) and gray matter (bottom) within control probands and relatives (n = 52), patient relatives (n = 36) and schizophrenia probands (n = 26). Results are shown after adjusting (more ...)