Whiter matter abnormalities in medication-naive subjects with a single short-duration episode of major depressive disorder

Abstract

Convergent studies have implicated white matter abnormalities in the pathophysiology of major depressive disorder (MDD). In this study, diffusion tensor imaging (DTI) was used to examine white matter abnormalities in 23 single-episode, medication-naive MDD participants versus 21 healthy control participants. Voxel-based analysis was used to investigate whole brain white matter abnormalities in the MDD group. Fractional anisotropy was significantly lower and apparent diffusion coefficient was significantly higher in the right superior longitudinal fasciculus (SLF) within the frontal lobe, right middle frontal and left parietal white matter in the MDD group compared with the healthy group.

Introduction

Convergent evidence suggests dysfunction of neural circuitry implicated in major depressive disorder (MDD) (Lockwood et al., 2002, Tekin and Cummings, 2002). Several brain regions, such as the frontal cortex, cingulate cortex, hippocampus, amygdala and parietal lobe, have been shown to be involved in this disorder by both morphometric (Tang et al., 2007, Andreescu et al., 2008, Egger et al., 2008, Vasic et al., 2008, Koolschijn et al., 2009) and functional (Wagner et al., 2008, Wang et al., 2008a, Wang et al., 2008b, Dichter et al., 2009, Matthews et al., 2009, Yang et al., 2009) magnetic resonance imaging (MRI) studies. Additional evidence from postmortem studies further supports the involvement of white matter which provides substantial connections within those regions in the pathophysiology of MDD. For example, altered deep white matter myelin staining and hyperintensities were observed in the prefrontal cortex in MDD subjects (Thomas et al., 2002; Regenold et al., 2007). Taken together with the findings on oligodendroglial density in the prefrontal cortex in MDD (Uranova et al., 2004), abnormalities of white matter within those circuitries may be directly relevant to the pathophysiology of MDD.

Diffusion tensor imaging (DTI), an MRI technique, can provide information about white matter microstructure integrity in vivo by measuring the magnitude and direction of water diffusion and has been used successfully to investigate white matter abnormalities in several psychiatric disorders (White et al., 2008). Two DTI measurements (Le Bihan et al., 2001) have been widely used in recent studies: fractional anisotropy (FA), which measures the principal directionality of water diffusion, and the apparent diffusion coefficient (ADC), which provides an overall evaluation of water diffusion. An increasing number of DTI studies have suggested that white matter abnormalities play a key role in MDD pathophysiology (Alexopoulos et al., 2002, Nobuhara et al., 2004, Taylor et al., 2004, Bae et al., 2006, Nobuhara et al., 2006, Li et al., 2007, Ma et al., 2007, Taylor et al., 2007, Yang et al., 2007, Alexopoulos et al., 2008, Taylor et al., 2008, Zou et al., 2008). However, results are inconsistent in these studies, probably due to differences in sample age, sex distribution, medication exposures, age of illness onset, illness duration and number of acute episodes. Additionally, different DTI methodologies, such as region of interest (Bae et al., 2006, Li et al., 2007, Taylor et al., 2008), fiber tracking (Malykhin et al., 2008), tract-based spatial statistics (Kieseppa et al., 2010) and voxel-based DTI (Ma et al., 2007, Zou et al., 2008), were applied in these studies, possibly contributing to differences in results as well. In order to minimize chronicity-related confounds and treatment variables, we performed a voxel-based DTI study to examine whole brain white matter abnormalities in single-episode, medication-naive MDD participants with duration of illness less than 3 months in the present study.