Accelerated white matter aging in schizophrenia: role of white matter blood perfusion

Abstract

Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia.

Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

“…Two studies showed decreased GM rCBF in the anterior cingulate and frontal regions in SZ versus controls (Kindler et al, 2013;Zhu et al, 2015) but two other studies reporting no differences in medial frontal regions (Ota et al, 2014;Pinkham et al, 2011), similar to our results. In terms of WM rCBF, one did not observe any differences in SZ while another observed that WM rCBF decreased with age and faster in SZ (Pinkham et al, 2011;Wright et al, 2014). Similarly, this study found an aging effect of AC WM rCBF, which is also consistent with work showing rCBF decrease across life span (Lu et al, 2011).…”

Reduced perfusion in normal‐appearing white matter in mild to moderate hypertension as revealed by 3D pseudocontinuous arterial spin labeling

“…Similar findings were reported by other groups as demonstrated recently by Wright et al 16 and Li et al 17 In the present study, 3D pCASL technique was performed to measure the regional CBF values of normalappearing white matter (NAWM) and various GM to detect the blood flow differences between hypertensive patients and controls further to investigate the potential hemodynamic changes in hypertension.…”

Applications of TMS to Study Brain Connectivity

“…Moreover, the magnitude of PPC-M1 connectivity correlated with severity and duration of illness, where patients with less impaired connectivity (i.e., more facilitation) had better global functioning, lower negative symptoms, and shorter illness duration. These results are also consistent with diffusion tensor imaging (DTI) studies showing altered patterns of white matter integrity (i.e., reduced fractional anisotropy) in patients with schizophrenia (Wright et al 2014;Fitzsimmons et al 2013) and overall provide evidence of dysfunctional PPC-M1 connectivity in schizophrenia.…”