Diffusion tensor tractography findings in schizophrenia across the adult lifespan

Abstract

In healthy adult individuals, late life is a dynamic time of change with respect to the microstructural integrity of white matter tracts. Yet, elderly individuals are generally excluded from diffusion tensor imaging studies in schizophrenia. Therefore, we examined microstructural integrity of frontotemporal and interhemispheric white matter tracts in schizophrenia across the adult lifespan. Diffusion tensor imaging data from 25 younger schizophrenic patients (< or = 55 years), 25 younger controls, 25 older schizophrenic patients (> or = 56 years) and 25 older controls were analysed. Patients with schizophrenia in each group were individually matched to controls. Whole-brain tractography and clustering segmentation were employed to isolate white matter tracts. Groups were compared using repeated measures analysis of variance with 12 within-group measures of fractional anisotropy: (left and right) uncinate fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, inferior occipito-frontal fasciculus, cingulum bundle, and genu and splenium of the corpus callosum. For each white matter tract, fractional anisotropy was then regressed against age in patients and controls, and correlation coefficients compared. The main effect of group (F(3,92) = 12.2, P < 0.001), and group by tract interactions (F(26,832) = 1.68, P = 0.018) were evident for fractional anisotropy values. Younger patients had significantly lower fractional anisotropy than younger controls (Bonferroni-corrected alpha = 0.0042) in the left uncinate fasciculus (t(48) = 3.7, P = 0.001) and right cingulum bundle (t(48) = 3.6, P = 0.001), with considerable effect size, but the older groups did not differ. Schizophrenic patients did not demonstrate accelerated age-related decline compared with healthy controls in any white matter tract. To our knowledge, this is the first study to examine the microstructural integrity of frontotemporal white matter tracts across the adult lifespan in schizophrenia. The left uncinate fasciculus and right cingulum bundle are disrupted in younger chronic patients with schizophrenia compared with matched controls, suggesting that these white matter tracts are related to frontotemporal disconnectivity. The absence of accelerated age-related decline, or differences between older community-dwelling patients and controls, suggests that these patients may possess resilience to white matter disruption.

Figure 1

White matter tracts of interest superimposed on fractional anisotropy grey scale images. (A) Left to right: left uncinate fasciculus, left inferior occipitofrontal fasciculus, left arcuate fasciculus. (B) Left to right: left inferior longitudinal fasciculus, right cingulum bundle, genu and splenium of corpus callosum (in same panel, both coloured red).

Figure 2

Fractional anisotropy by diagnostic-age group for 12 white matter tracts. *Significant differences (that survived Bonferroni correction) between young controls and young schizophrenic patients are noted on the figure: left uncinate fasciculus t₄₈ = 3.7, P = 0.001; and right cingulum bundle t₄₈ = 3.6, P = 0.001. L UF = left uncinate fasciculus; R UF = right uncinate fasciculus; L IFOF = left inferior occipitofrontal fasciculus; R IFOF = right inferior occipitofrontal fasciculus; L AF = left arcuate fasciculus; R AF = right arcuate fasciculus; L ILF = left inferior longitudinal fasciculus; R ILF = right inferior longitudinal fasciculus; L CB = left cingulum bundle; R CB = right cingulum bundle; G CC = genu of corpus callosum; S CC = splenium of corpus callosum.

Figure 3

Relationship between age and fractional anisotropy for each white matter tract in both schizophrenic patients and healthy controls. No significant differences (when comparing correlation coefficients) in age-related decline of fractional anisotropy were present in any white matter tract between schizophrenic patients and controls.

Figure 3

Relationship between age and fractional anisotropy for each white matter tract in both schizophrenic patients and healthy controls. No significant differences (when comparing correlation coefficients) in age-related decline of fractional anisotropy were present in any white matter tract between schizophrenic patients and controls.