Prefrontal white matter abnormalities in young adult with major depressive disorder: A diffusion tensor imaging study

Abstract

Prefrontal impairments have been hypothesized to be most strongly associated with the cognitive and emotional dysfunction in depression. Recently, white matter microstructural abnormalities in prefrontal lobe have been reported in elderly patients with major depressive disorder (MDD) using diffusion tensor imaging (DTI). However, it is still unclear whether the same changes exist in younger patients. In the present study, we first utilized DTI to detect prefrontal white matter in young adults with MDD. Nineteen first-episode, untreated young adults with MDD and twenty age- and gender-matched healthy controls were recruited. DTI and localizing anatomic data were acquired. Then, the regions of interest (ROIs) were located in prefrontal white matter at 4 mm inferior, and 0, 4, 8, 12, 16 and 20 mm superior to the anterior commissure–posterior commissure (AC–PC) plane, respectively. Compared with healthy controls, patients with MDD showed significantly lower fractional anisotropy (FA) values in prefrontal white matter at bilateral 20 mm, right 16 mm and right 12 mm above the AC–PC. Furthermore, there was no significant correlation between the FA value of any ROI and illness course as well as severity of depression. Together with previous findings, the present results suggest that microstructural abnormalities in prefrontal white matter may occur early in the course of MDD and may be related to the neuropathology of depression throughout adulthood from young to elderly.

Introduction

Existing evidence, such as that shown in morphometric and functional imaging studies, suggests prefrontal impairments in patients with major depressive disorder (MDD). On the one hand, magnetic resonance imaging (MRI) studies found reduced prefrontal lobe volume in depression (Kumar et al., 2000), including both its gray matter (Coffey et al., 1993, Drevets et al., 1997, Kumar et al., 1998) and white matter (Bell-McGinty et al., 2002). On the other hand, functional imaging studies demonstrated lower glucose metabolism and cerebral blood flow in prefrontal cortex in depressed patients (Baxter et al., 1989, Mayberg et al., 1999, Nobler et al., 2000). Moreover and specifically, MRI (Coffey et al., 1993, Coffey et al., 1990, Soares and Mann, 1997) and postmortem (Thomas et al., 2002) studies showed deep white matter hyperintensities at the level of prefrontal cortex in late-life depression.

Currently, diffusion tensor imaging (DTI), a new MRI technique, has also been used to study white matter and neural fiber tracts by measuring the movement of water molecules. Such studies in depression have reported microstructural white matter abnormalities in widespread prefrontal regions (Taylor et al., 2004, Nobuhara et al., 2004, Nobuhara et al., 2006, Bae et al., 2006, Alexopoulos et al., 2002) and found prefrontal white matter alterations to be linked to neuropsychological function (Murphy et al., 2007). Moreover, Rusch et al. (2007) reported an association between a lifetime history of major depression and inferior frontal white matter integrity among women with borderline personality disorder. However, all these DTI studies recruited elderly patients, and no published DTI studies have detected the white matter integrity of prefrontal lobe in young adult depressed patients. Despite growing evidence supported prefrontal cortical abnormalities in younger as well as elderly depression (Botteron et al., 2002), postmortem study reported reduction of packing density and glial cells number in dorsolateral prefrontal cortex only in older rather than younger depressive patients (Miguel-Hidalgo et al., 2000). These complex findings cause a puzzle on what changes would be in white matter integrity of prefrontal lobe in young adult depression. However, it is worthy of clarifying such changes. Thus, we designed this study to determine if the prefrontal white matter microstructure of untreated young depressed adults is impaired in a pattern that is similar to the impairments found in older depressed adults.