White matter tractography in bipolar disorder and schizophrenia.
ABSTRACT Abnormalities of white matter integrity have been repeatedly demonstrated in both schizophrenia and bipolar disorder with voxel based methods. Because these methods are limited in their ability to localize deficits to specific tracts, we sought to investigate alterations in fractional anisotropy (FA) in the uncinate fasciculus and anterior thalamic radiation with probabilistic tractography.
Individuals with schizophrenia (n = 25) or bipolar disorder (n = 40) were recruited from families with two or more affected members and age-matched to a control group (n = 49). All participants underwent diffusion tensor magnetic resonance imaging that was subsequently analyzed with probabilistic tractography. Mean FA was calculated bilaterally for the uncinate and anterior thalamic radiation and compared between groups with repeated measures analysis of variance.
Patients with schizophrenia or bipolar disorder showed common reductions in the uncinate fasciculus and anterior thalamic radiation. These reductions were unrelated to age, duration of illness, current medication, or current psychiatric symptoms in all patients or the lifetime presence of psychotic symptoms in bipolar subjects.
Patients with schizophrenia or bipolar disorder show common abnormalities in the uncinate fasciculus and anterior thalamic radiation that fail to respect traditional diagnostic boundaries. These deficits might be related to shared risk factors and disease mechanisms common to both disorders.
[Show abstract] [Hide abstract]
ABSTRACT: White matter (WM) abnormalities are among the most commonly reported neuroimaging findings in bipolar disorder. Nonetheless, the specific nature and pathophysiology of these abnormalities remains unclear. Use of a combination of magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) permits examination of myelin and axon abnormalities separately. We aimed to examine myelination and axon geometry in euthymic patients with bipolar disorder with psychosis (BDP) by combining these two complementary non-invasive MRI techniques. We applied a combined MRI approach using MTR to study myelin content and DTS to study metabolite (NAA) diffusion within axons in patients with BDP (n=21) and healthy controls (n=24). Data were collected from a 1 × 3 × 3 cm voxel within the right prefrontal cortex WM at 4 Tesla. Clinical and cognitive data were examined in association with MTR and DTS data. MTR was significantly reduced in BDP, suggesting reduced myelin content. The apparent diffusion coefficient of N-acetylaspartate (NAA) did not differ from healthy controls, suggesting no changes in axon geometry in patients with BDP. These findings suggest that patients with BDP exhibit reduced myelin content, but no changes in axon geometry compared to controls. These findings are in contrast with our recent findings, using the same techniques, in patients with schizophrenia (SZ), which suggest both myelination and axon abnormalities in SZ. This difference may indicate that alterations in WM in BDP may have unique causes and may be less extensive than WM abnormalities seen in SZ.Neuropsychopharmacology accepted article preview online, 20 November 2014. doi:10.1038/npp.2014.310.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2014; 40(5). DOI:10.1038/npp.2014.310 · 8.68 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Neuropsychological deficits constitute enduring trait-like features in bipolar disorder (BD), and persist in euthymia. White matter (WM) abnormalities are one of the most consistently reported findings in neuroimaging studies of BD. We hypothesized that neuropsychological performances could correlate with WM integrity in a sample of bipolar patients in core WM tracts. Seventy-eight patients affected by BD were evaluated for verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency through the Brief Assessment of Cognition in Schizophrenia. White matter integrity was evaluated using DTI and tract-based spatial statistics with threshold free cluster enhancement (p>0.949). We observed that cognitive performances in attention and information processing, working memory, executive functions and psychomotor coordination were associated with DTI measures of WM integrity in several association fibres: inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, cingulum bundle, corpus callosum, and corona radiata. The drug treatments administered during the course of the illness could have influenced DTI measures and neurocognitive function. Other limitations include issues such as generalizability due to the lack of a control group, possible undetected past comorbidities, population stratification, and the presence of a 28% of patients which previously experienced delusions. This is the first study to use a validated cognitive battery to investigate the principal cognitive domains in BD. Our data confirm the importance of WM integrity as a neurobiological underpinning of cognitive deficits. Copyright © 2014 Elsevier B.V. All rights reserved.Journal of Affective Disorders 12/2014; 174C:342-352. DOI:10.1016/j.jad.2014.12.030 · 3.76 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: White matter (WM) abnormalities are one of the most widely and consistently reported findings in schizophrenia (SZ) and bipolar disorder (BD). If these abnormalities are inherited determinants of illness, suitable to be classified as an endophenotype, relatives of patients must also have them at higher rate compared to the general population. In this review, we evaluate published diffusion tensor imaging (DTI) studies comparing first degree relatives of SZ and BD patients and healthy control subjects. We searched PubMed, Embase and PsychInfo for DTI studies which included an unaffected relative and a healthy comparison group. 22 studies fulfilled the inclusion criteria. WM abnormalities were found in many diverse regions in relatives of SZ patients. Although the findings were not completely consistent across studies, the most implicated areas were the frontal and temporal WM regions and the corpus callosum. Studies in relatives of BD patients were fewer in number with less consistent findings reported across studies. Our review supports the concept of WM abnormalities as an endophenotype in SZ, with somewhat weaker evidence in BD, but larger and higher quality studies are needed to make a definitive comment. Copyright © 2014 Elsevier B.V. All rights reserved.Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.12.008 · 4.43 Impact Factor