Brief report
Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics

https://doi.org/10.1016/j.jad.2009.04.023Get rights and content

Abstract

Background

A few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics.

Methods

Sixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans.

Results

Compared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions.

Limitations

Possibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies.

Conclusions

A novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.

Introduction

The major affective disorders, including recurrent major depressive disorder (MDD), are associated with minor structural brain abnormalities (Campbell and MacQueen, 2006), including changes in white matter (Videbech and Ravnkilde, 2004). A relatively consistent finding has been the increased occurrence of white matter hyperintensities (WMH) among elderly unipolar patients, but for younger patients the evidence is equivocal (Soares and Mann, 1997, Videbech, 1997, Thomas et al., 2002).

Microstructural properties of white matter can be probed with magnetic resonance imaging (MRI) using a relatively novel technique, diffusion tensor imaging (DTI) (Basser, 1995, Le Bihan et al., 2001). It is sensitive to pathological changes in tissue observed as changes in fractional anisotropy (FA) or other measures derived from the diffusion tensor. Both depressive patients and controls have shown decreased FA in the WMH (Taylor et al., 2001). The DTI studies of MDD patients have revealed frontal and temporal white matter abnormalities in late-life depression (Alexopoulos et al., 2002, Taylor et al., 2004, Nobuhara et al., 2006, Yang et al., 2007). A recent voxel-based morphometry (VBM) study reported lower FA in frontal, temporal, and parietal lobes in first-episode, treatment-naïve young adults with MDD (Ma et al., 2007).

Earlier DTI studies on affective disorders have used mainly the region-of-interest (ROI) method. This method has several shortcomings; the manual placement of ROIs on thin tracts may be difficult (Smith et al., 2006), and the method can detect changes only in the areas where the ROIs are placed. Smith et al. (2006) have recently suggested a new automated tract-based spatial method (TBSS) as part of the FSL program which is expected to improve the objectivity and interpretability of analysis of DTI studies. Furthermore, TBSS was developed to alleviate the alignment problems related to standard use of VBM. It projects individual subjects' FA data into a common space in a way that is not dependent on perfect nonlinear registration, which should be guaranteed in VBM. No spatial smoothing is necessary, unlike in VBM, where the amount of smoothing can greatly affect the final results.

To our knowledge this is the first DTI study of patients with MDD using TBSS for the analyses. We presumed that a decrease in FA, a sign of disintegration, would be found in middle-aged MDD patients, located in regions connecting emotion related limbic and cortical areas.

Section snippets

Participants

Sixteen outpatients (14 female, 2 male) with DSM-IV MDD were recruited from research interviews of two clinical studies (Melartin et al., 2002, Vuorilehto et al., 2005, Holma et al., 2007). The 20 healthy controls (10 female, 10 male) were recruited from a general population survey (Jylha and Isometsa, 2006).

The subjects with MDD and the controls were diagnosed by using the Structured Clinical Interview for DSM-IV (SCID-I/P) (Vuorilehto et al., 2005, Holma et al., 2007). The patients were

Results

Although MDD patients showed several areas of decreased FA compared with controls, none of the differences exceeded the 95% confidence level (Model 1). Patients showed a trend of decreased FA in the left sagittal stratum (p = 0.066, corrected for multiple comparisons) (Fig. 1). The results with cluster size and the most significant MNI mm coordinates are presented in Table 1. Suggestive areas of decreased FA in patients were found in the posterior body of corpus callosum and right midcingulate

Discussion

We found that middle-aged patients with MDD had marginally reduced FA in a white matter region located in the left sagittal stratum (Fig. 1). Regressing out effects of clinical variables like the duration and severity of disorder did not change the result. The inferior fronto-occipital fasciculus (IFO) runs through the sagittal stratum area together with the inferior longitudinal fasciculus (ILF) (Mori et al., 2005). The IFO has connections to the inferior and lateral margins of the occipital

Conclusions

To our knowledge this is the first study to show that patients with MDD had decreased FA in the left sagittal stratum compared with controls. Three important white matter tracts run through this area. They contribute to the limbic-cortical neural network and visual system region, and the structural changes revealed in this study may contribute to the dysfunction detected in the limbic-cortical network in depressive patients (Mayberg, 2003).

Role of funding source

This work was supported by the Finnish Academy grant no. 21 1000, the Instrumentarium Science Foundation, the Department of Psychiatry, HUCH, the Department of Radiology, HUCH, and the Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki. None of these organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

Dr. Kieseppä has received honoraria from Lilly. Dr. Tuulio-Henriksson has received honoraria from Lilly, Orion Pharma, and Janssen Cilag. Dr. Melartin has received honoraria from Lilly, Whyet, Lundbeck, and Boehringer Ingelheim, and is a member of the Advisory Board of Lundbeck. Dr. Isometsä has received honoraria from Astra Zeneca, GSK, Lilly, Lundbeck, and Pfizer. All other authors declare that they have no conflicts of interest.

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