Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder

Department of Psychiatry, Pediatric Brain Research and Intervention Center, University of Illinois at Chicago, IL 60608, USA.
Bipolar Disorders (Impact Factor: 4.97). 08/2012; 14(6):597-606. DOI: 10.1111/j.1399-5618.2012.01045.x
Source: PubMed


White-matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white-matter deviation may be more pronounced in pediatric than adult-onset BD. The present study aimed to examine how white-matter microstructure deviates from a typical maturational trajectory in BD.
Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9-42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract-based spatial statistics were used to examine the center of white-matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post-hoc analyses.
The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult-onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity.
The ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater susceptibility to illness.

Download full-text


Available from: John A Sweeney, Nov 17, 2015
  • Source
    • "These parameters give an in vivo measure of water diffusion parallel and perpendicular to WM fibers and reflect axonal and myelin integrity respectively (Beaulieu, 2002). RD values have been found increased at the onset of BD (Lu et al., 2012) and when comparing BD patients to those with unipolar depression (Benedetti et al., 2011) or unchanged in elderly BD (Haller et al., 2011). However, most of the above mentioned studies focused on patients suffering from BD-I; only a few included mixed groups of BD-I and BD-II (Bruno et al., 2008; Mahon et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Diffusion tensor imaging (DTI) studies of bipolar disorder (BD) report contrasting results and are mainly focused on bipolar I (BD-I) samples. We aimed at investigating how and where DTI parameters differ between BD-I and bipolar II (BD-II) and between BD and healthy control subjects (HC). Methods: We conducted a tract-based spatial statistics analysis of DTI derived parameters, namely fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) in a matched sample of 50 BD (25 BD-I and 25 BD-II) during the chronic course of the illness and 50 HC. Results: Compared to BD-I and HC, BD-II showed lower FA but no significant AD or RD differences in the right inferior longitudinal fasciculus (ILF). Both patient groups showed lower AD and RD in the left internal capsule and lower AD across the left ILF, the cortico-spinal tract within the right hemisphere and bilaterally in the cerebellum with respect to HC. Limitations: Patients were medicated at the time of scanning; the BD-II group had higher Hamilton Rating Scale for Depression scores than the BD-I group. Conclusions: BD-II patients differ from BD-I in the ILF. Both BD subtypes showed widespread white matter (WM) changes in the internal capsule, cortico-spinal tract and cerebellum. The loss of WM integrity in BD-II might be due to demyelination whereas WM changes common to both subgroups could be attributable to axonal damage.
    Journal of Affective Disorders 09/2015; 189. DOI:10.1016/j.jad.2015.09.035 · 3.38 Impact Factor
  • Source
    • "DTI whole brain studies using tract-based spatial statistics (TBSS) address some of the limitations of VBM, such as registration of images to a common template, smoothing kernel selection, and adjusting for partial volume effects, via a skeletonization process (Smith et al., 2006). Studies of adolescents with BD using TBSS have found WM aberrations in the CC, fornix, cingulate, and parietal/ occipital corona radiata (Barnea-Goraly et al., 2009; James et al., 2011; Lu et al., 2012; Gao et al., 2013b). In summary, previous studies in adults and youth with BD suggest WM tract aberrations in limbic circuitry and major association and commissural tracts. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 02/2015; 6(2). DOI:10.1016/j.pscychresns.2015.02.007 · 2.42 Impact Factor
  • Source
    • "A correlation analysis between DTI measures and the delta of HDRS scores (difference between HDRS scores after treatment and HDRS scores at baseline) was then performed in the areas where a difference in WM integrity between responders and non responders was observed. We accounted for the effects of nuisance covariates which could influence WM structure: age (Kochunov et al., 2007), sex (Herting et al., 2011), education (Foubert-Samier et al., 2012), age at onset of the illness (Lu et al., 2012), and duration of lithium treatment in months (Benedetti et al., 2013). Threshold-free cluster enhancement (TFCE) (Smith and Nichols, 2009) was used to avoid defining arbitrary cluster-forming thresholds and smoothing levels. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes of white matter (WM) microstructure have been proposed as structural biomarkers of bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been proposed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response. We tested if baseline DTI measures can predict response to treatment in 70 in-patients affected by a major depressive episode in the course of BD, treated with chronotherapeutics for one week. We performed whole-brain tract-based spatial statistics with threshold-free cluster enhancement for the DTI measures of WM microstructure integrity: fractional anisotropy, axial, radial, and mean diffusivity. Increased mean and radial water diffusivity correlated with poor antidepressant response to TSD+LT in core WM tracts which are crucial for the functional integrity of the brain, including corpus callosum, corona radiata, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and thalamic radiation. Limitations include issues such as generalizability, possible population stratification, medications and their effects on DTI measures, and no placebo control for chronotherapeutics. We could not consider other factors such as gene-environment interactions. The association of increased radial and mean diffusivity with poor response to chronotherapeutic treatment warrants interest for the study of DTI measures of WM microstructure as markers for treatment response in bipolar depression. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 11/2014; 174C:233-240. DOI:10.1016/j.jad.2014.11.010 · 3.38 Impact Factor
Show more