Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

Abstract

The objective of this study was to investigate the clinical and neuropsychological correlates of white matter abnormalities in patients with schizophrenia studied early in the course of illness. A total of 33 (21 male/12 female) patients with recent onset schizophrenia and 30 (18 male/12 female) healthy volunteers completed structural and diffusion tensor imaging exams. Patients also received clinical and neuropsychological assessments. Fractional anisotropy (FA) maps were compared between groups in the white matter using a voxelwise analysis following intersubject registration to Talairach space and correlated with functional indices. Compared to healthy volunteers, patients demonstrated significantly (po0.001, cluster size X100) lower FA within temporal lobe white matter regions corresponding approximately to the right and left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. There were no areas of significantly higher FA in patients compared to healthy volunteers. Lower FA in the bilateral uncinate fasciculus correlated significantly with greater severity of negative symptoms (alogia and affective flattening), and worse verbal learning/memory functioning. In addition, higher FA in the inferior fronto-occipital fasciculus correlated significantly with greater severity of delusions and hallucinations. White matter abnormalities are evident in patients with schizophrenia early in the course of illness, appearing most robust in left temporal regions. These abnormalities have clinical and neuropsychological correlates, which may be useful in further characterizing structure-function relations in schizophrenia and constraining neurobiological models of the disorder.

ErbB4 Genotype Predicts Left Frontotemporal Structural Connectivity in Human Brain

“…It is therefore of interest that the functional relevance of ErbB4Fvia its possible impact on the structural integrity of these fiber tractsFis further supported, ie externally validated, by our additional finding that FA was also related to RT which itself is frequently impaired in schizophrenia and which has been proposed to be an endophenotype of schizophrenia (Filbey et al, 2008). In this context, it is worth mentioning that several earlier studies have linked poor neurocognitive performance with reduced FA in frontotemporal fiber tracts (Szeszko et al, 2008). At the same time, our finding that the schizophrenia risk genotype predicts RT in the expected direction largely concurs with another study, which has reported ErbB4 genotype effects on neurocognitive measures in healthy controls (Nicodemus et al, 2006).…”

“…An increasing body of evidence from neuroimaging and postmortem studies also suggests that structural connectivity between brain regions is disturbed in schizophrenia and that altered myelination mayFin partFaccount for this deficit . In particular, the frequently made observation in functional imaging and electrophysiological studies that left frontotemporal connectivity might be preferentially affected in schizophrenic patients and their relatives has recently obtained support from several microstructural imaging studies Szeszko et al, 2008). However, it is currently unknown what molecular mechanisms may account for the deficiency of structural connectivity in schizophrenia illness.…”

“…Voxel-based FA contrast analysis was then done to compare genotype groups using general linear model (GLM) standard two sample unpaired t-test. Following established procedures (Shin et al, 2005;Szeszko et al, 2008), contrast maps were thresholded at a Po0.001 without correction for multiple comparisons and the extent threshold for significant clusters was set to 40 voxels.…”

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

“…[40][41][42] Moreover, recent functional MRI studies have indicated that functional connectivity in the prefrontal cortex increases with the severity of psychotic symptoms, especially in the early stage of schizophrenia. 43,44 As functional hyperconnectivity may be reflected in regional FA increases, [40][41][42] our findings of both positive and negative associations with positive symptoms in 2 closely linked anatomical structures (AF and SLF) support the idea that psychotic symptoms arise from regional irregularities in white matter rather than deficits per se.…”

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

“…Several additional regions beyond the callosal body have been implicated in chronic schizophrenia including SLF (Rotarska-Jagiela et al, 2009;Rowland et al, 2009;Seok et al, 2007;Shergill et al, 2007;Szeszko et al, 2008) DMRI study in severe chronic schizophrenia L Holleran et al Jagiela et al, 2009;Seal et al, 2008), UF (Burns et al, 2003;McIntosh et al, 2008;Miyata et al, 2010;Mori et al, 2007b;Seal et al, 2008), internal capsule (Buchsbaum et al, 1998;Lim et al, 1999), external capsule (Rotarska-Jagiela et al, 2009;Seal et al, 2008), cingulum (Kubicki et al, 2003;Mori et al, 2007b;Seok et al, 2007;Sun et al, 2003;Wang et al, 2004), fornix (Fitzsimmons et al, 2009;Kuroki et al, 2006), anterior commissure (Choi et al, 2011), arcuate fasciculus (Burns et al, 2003;Phillips et al, 2009), and cerebellar peduncles (Okugawa et al, 2006;Seok et al, 2007). Differences in RD are less examined, yet to date increases have been detected in the external capsule (Seal et al, 2008), in the left inferior temporal and left occipital lobe (Ashtari et al, 2007), in temporal WM (Koch et al, 2011), and in the middle cerebellar peduncle (Okugawa et al, 2006), and increased mean diffusivity has been detected in the splenium of the corpus callosum (Foong et al, 2000).…”