Microstructural white matter changes are correlated with the stage of psychiatric illness

Abstract

Microstructural white matter changes have been reported in the brains of patients across a range of psychiatric disorders. Evidence now demonstrates significant overlap in these regions in patients with affective and psychotic disorders, thus raising the possibility that these conditions share common neurobiological processes. If affective and psychotic disorders share these disruptions, it is unclear whether they occur early in the course or develop gradually with persistence or recurrence of illness. Utilisation of a clinical staging model, as an adjunct to traditional diagnostic practice, is a viable mechanism for measuring illness progression. It is particularly relevant in young people presenting early in their illness course. It also provides a suitable framework for determining the timing of emergent brain alterations, including disruptions of white matter tracts. Using diffusion tensor imaging, we investigated the integrity of white matter tracts in 74 patients with sub-syndromal psychiatric symptoms as well as in 69 patients diagnosed with established psychosis or affective disorder and contrasted these findings with those of 39 healthy controls. A significant disruption in white matter integrity was found in the left anterior corona radiata and in particular the anterior thalamic radiation for both the patients groups when separately contrasted with healthy controls. Our results suggest that patients with sub-syndromal symptoms exhibit discernable early white matter changes when compared with healthy control subjects and more significant disruptions are associated with clinical evidence of illness progression.

Figure 1

The left anterior corona radiata (ACR), the region of significantly decreased fractional anisotropy is the conjunction of three major association fibres, the anterior thalamic radiation (blue), the inferior fronto-occipital fasciculus (yellow) and the uncinate fasciculus (red). The green box illustrates the ACR region of interest and a magnified view of the crossing fibres.

Figure 2

Panel (a): The top row displays the contrast between controls and Stage 1B patients and shows a regions of decreased (P=0.01 uncorrected) fractional anisotropy (FA) in the left anterior corona radiata for the Stage 1B patients. Panel (b) displays the contrast between controls and Stage 2/3 patients that highlights the involvement of the identical region, which has significantly decreased FA (P=0.033, corrected). Panel (c) is a graphical overlay of the FA results for Stage 1B and Stage 2/3 patients along with the coregistered fibre tracts for anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF). Both contrast shown in panels (a) and (b) have undergone threshold free cluster enhancement. All images are radiologically oriented.

Figure 3

Illustrates the region of significantly increased λ⊥ for the Stage 2/3 group that is constrained within the anterior corona radiata region of interest, which indicates abnormal diffusion of water across the myelin sheath. The three converging fibre tracts are superimposed (anterior thalamic radiation—green; inferior fronto-occipital fasciculus—purple; uncinate fasciculus—red). The contrast has undergone threshold free cluster enhancement. All images are radiologically oriented.

Figure 4

Illustrates the relative contribution of the anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus (UF) fibre tracts that converge through the anterior corona radiata region of interest. Panels (a) and (b) illustrate that the ATR is the predominant fibre tract that contributes to the mean fractional anisotropy (FA) across the groups. Panel (c) illustrates the corrected FA measures for the controls (NL), Stage 1B and Stage 2/3 groups. **P<0.05.