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 demonstrated involvement in this disorder by both morphometric (Andreescu et al., 2008; Egger et al., 2008; Koolschijn et al., 2009; Tang et al., 2007; Vasic et al., 2008) and functional (Dichter et al., 2009; Matthews et al., 2009; Wagner et al., 2008; Wang et al., 2008a; Wang et al., 2008b; Yang et al., 2009) magnetic resonance imaging (MRI) studies. Additional evidence from postmortem studies further supports the involvement of white matter which providessubstantial connections within those regions in the pathophysiology of MDD. For example, altered deep white matter myeline staining and hyperintensities were observed in the prefrontal cortex in MDD subjects (Regenold et al., 2007; Thomas et al., 2002). 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), fractional anisotropy (FA) measuring the principle directionality of water diffusion and apparent diffusion coefficient (ADC) providing the overall evaluation of the water diffusion, have been widely used in recent studies. Increasing DTI studies have suggested that white matter abnormalities play a key role in MDD pathphysiology (Alexopoulos et al., 2002; Alexopoulos et al., 2008; Bae et al., 2006; Li et al., 2007; Ma et al., 2007; Nobuhara et al., 2004; Nobuhara et al., 2006; Taylor et al., 2008; Taylor et al., 2007; Taylor et al., 2004; Yang et al., 2007; 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 base 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.