Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Abstract

Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age-and gender-matched healthy controls using a 64 gradient direction sequence, (b ¼ 1300 s/mm 2 ) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

Left-hemisphere lateralization for language and interhemispheric fiber tracking in patients with schizophrenia

“…This abnormality was indicated by decreased FA and increased RD. In agreement with our findings, neuroimaging studies showed lower callosal integrity (through FA or RD) in either the whole CC (Miyata et al, 2010;Knochel et al, 2012;Freitag et al, 2013) or, more specifically, in the splenium region (Kyriakopoulos et al, 2008;Clemm von et al, 2014;Holleran et al, 2014;Balevich et al, 2015). These results were congruent with the investigated interhemispheric tract, since its projection, connecting homologue temporal cortical regions, crosses the splenium region.…”

Comparing free water imaging and magnetization transfer measurements in schizophrenia

“…More recent studies that use tract-based spatial statistics (Smith et al, 2006) reveal a similar pattern (Clemm von Hohenberg et al, 2013; Douaud et al, 2007; Freitag et al, 2013; Fujino et al, 2014; Guo et al, 2012; Holleran et al, 2013; Jeong et al, 2009; Karlsgodt et al, 2009; Karlsgodt et al, 2008; Lee et al, 2013; Liu et al, 2013). Of note, none of the aforementioned studies corrected the FA measure for free-water contamination, and it is likely that such correction would decrease the extent of lower FA values, as demonstrated by Pasternak et al (Pasternak et al, 2012).…”

Neuroimaging findings in treatment-resistant schizophrenia: A systematic review

“…One investigation specifically compared treatment-resistant auditory verbal hallucinations (TR-AVH) and absence of AVH (Kubera et al, 2014). The available structural neuroimaging literature suggests a link between neuroanatomical abnormalities and TRS, including anomalies in the corpus callosum (CC) compared with HC (Holleran et al, 2014; Sun et al, 2009). It remains unclear whether neuroanatomical changes may be related to CLZ response in TRS.…”

“…Zugman et al (2013) reported that patients with TRS demonstrated a reduction in cortical thickness in the frontal, parietal, temporal and occipital regions versus HC (Zugman et al, 2013). White matter abnormalities have also been linked to TRS; when compared with HC, patients with CLZ-naïve TRS showed reductions in fractional anisotropy and increases in radial diffusivity in the CC and in the temporal lobe areas of cortico-cortical white matter association tracts, which were negatively related to duration of illness (Holleran et al, 2014). These findings raise the possibility that there exist deficits in the microstructural organization of white matter within these areas in TRS.…”