White Matter Density in Patients with Schizophrenia, Bipolar Disorder and Their Unaffected Relatives

Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, Scotland, UK.
Biological Psychiatry (Impact Factor: 10.26). 09/2005; 58(3):254-7. DOI: 10.1016/j.biopsych.2005.03.044
Source: PubMed


This study sought to assess white matter density in patients and relatives with histories of bipolar disorder and/or schizophrenia.
Subjects included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives of the three patient groups were also recruited. Subjects underwent an MRI brain scan which was analyzed using a white-matter optimized technique.
Subjects with schizophrenia and bipolar disorder showed reduced white matter density in the anterior limb of the internal capsule which was not found in unaffected relatives. Reductions were found in frontal subgyral white matter density in affected subjects with a family history of schizophrenia only.
Abnormal anterior internal capsule white matter may provide a structural substrate for both disorders.

9 Reads
  • Source
    • "We therefore interpreted the changes as most likely attributable to the internal capsule. Abnormalities of white matter density of the internal capsule have been described previously in schizophrenia patients (Zhou et al. 2003; McIntosh et al. 2005). Also, a study on the NRG1 rs6994992 variant reported reduced white matter integrity in the anterior limb of the internal capsule (McIntosh et al. 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis. We compared fractional anisotropy in 54 subjects that were either homozygous for the risk C allele carriers (n = 31) for rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for diffusion data analysis, was used to improve white matter registration and to focus the statistical analysis to major fiber tracts. Statistical analysis showed that homozygous risk C allele carriers featured elevated fractional anisotropy (FA) in the right perihippocampal region and the white matter proximate to the left area 4p as well as the right hemisphere of the cerebellum. We found three clusters of reduced FA values in homozygous C allele carriers: in the left superior parietal region, the right prefrontal white matter and in the deep white matter of the left frontal lobe. Our results highlight the importance of Neuregulin-1 for structural connectivity of the right medial temporal lobe. This finding is in line with well known neuropathological findings in this region in patients with schizophrenia.
    Brain and Behavior 03/2014; 4(2):215-26. DOI:10.1002/brb3.203 · 2.24 Impact Factor
  • Source
    • "Despite the increasing number of DTI studies in affective disorders, the current amount of evidence for WM morphometry in BD is still limited. Only five studies to date have evaluated regional WM volumes in BD patients (Bruno et al., 2004; McIntosh et al., 2005; Nugent et al., 2006; Scherk et al., 2008; Tost et al., 2010) and their unaffected relatives (McIntosh et al., 2005; van der Schot et al., 2009) – none recruiting first-episode patients – with conflicting results. To our knowledge, there are no studies assessing WM volume abnormalities in psychotic MDD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n=40) relative to controls (n=89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness.
    Psychiatry Research 07/2012; 202(3):198-205. DOI:10.1016/j.pscychresns.2011.09.005 · 2.47 Impact Factor
  • Source
    • "Although these diseases are distinct in nature, they share some WM distortions that may contribute to their pathophysiology , including reduced oligodendrocyte number and expression of myelin constituents (for recent reviews, see Matute, 2010; Stys, 2011). Neuropathological studies have revealed myelin defects and oligodendrocyte alterations in brain tissue from schizophrenic patients, correlating with the decreased expression of myelin-related genes (McIntosh et al., 2005). For instance, histological studies have demonstrated an abnormal distribution and decreased density of oligodendrocytes in the frontal regions of the cerebral cortex in schizophrenic patients, as well as reduced cell numbers in certain cortical layers (Uranova et al., 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The phylogenetic enlargement of cerebral cortex culminating in the human brain imposed greater communication needs that have been met by the massive expansion of WM (white matter). Damage to WM alters brain function, and numerous neurological diseases feature WM involvement. In the current review, we discuss the major features of WM, the contributions of WM compromise to brain pathophysiology, and some of the mechanisms mediating WM injury. We will emphasize the newly appreciated importance of neurotransmitter signalling in WM, particularly glutamate and ATP signalling, to understanding both normal and abnormal brain functions. A deeper understanding of the mechanisms leading to WM damage will generate much-needed insights for developing therapies for acute and chronic diseases with WM involvement.
    ASN Neuro 02/2012; 4(2). DOI:10.1042/AN20110060 · 4.02 Impact Factor
Show more