Introduction
The micro-integrity of white matter (WM) is measured with fractional anisotropy (FA). It is important for the transmission of signals through the fasciculus and might play a role in the pathophysiology of psychiatric illnesses. Major depressive disorder (MDD) consists of depressive symptoms, and cognitive and social functional impairments. The above symptoms could be associated with the neurophysiological dysfunctions of MDD. The micro-integrity of WM might play an important role in the pathophysiology of MDD. A ‘limbic-cortico-striato-pallido-thalamic’ circuit model for depression has been proposed, which involves the above structures through connecting WM tracts (Sheline, Reference Sheline2000). The model suggests that WM tracts might influence message transmission between the structures and lead to the development of MDD.
There are several studies that discuss the role of fasciculus WM in the pathogenesis of MDD. Zou et al. (Reference Zou, Huang, Li, Gong, Li, Ou-yang, Deng, Chen, Li, Ding and Sun2008) reported that decreased FA could be observed in the left superior longitudinal fasciculus (SLF) and internal capsule of patients who have late-onset MDD; this study suggested that cortico-subcortical circuits could be involved in the aetiology of MDD (Zou et al. Reference Zou, Huang, Li, Gong, Li, Ou-yang, Deng, Chen, Li, Ding and Sun2008). Another study of late-onset MDD showed that a higher density of WM lesions in the left SLF and corpus callosum (CC) might disturb the control of cognitive and affective functions (Dalby et al. Reference Dalby, Chakravarty, Ahdidan, Sorensen, Frandsen, Jonsdottir, Tehrani, Rosenberg, Ostergaard and Videbech2010a ). A recent meta-analysis showed that lower FA values in the left SLF could play an important role in the pathophysiology of MDD (Murphy & Frodl, Reference Murphy and Frodl2011). The above results support possible alterations in the WM integrity of the SLF and subcortical WM structures. The SLF is related to higher cortical functions, such as language and cognitive functions. It connects the posterior language region with the precentral gyrus and Broca's regions to form a circuit for higher cortical functions (Bernal & Altman, Reference Bernal and Altman2010). Alterations in the SLF might influence cognitive and language functions, which are also impaired in MDD.
Apart from the SLF, the anterior thalamic radiation (ATR) might be another region that has a lower FA and could be involved in the aetiology of MDD. Sexton et al. (Reference Sexton, Le Masurier, Allan, Jenkinson, McDermott, Kalu, Herrmann, Bradley, Mackay and Ebmeier2012) suggested that late-onset MDD could be associated with alterations in the WM micro-integrity of the ATR and that earlier age-onset MDD might be related to reduced hippocampal volume. These findings are compatible with the hypotheses of vascular and glucocorticoid cascades for MDD. The ATR interacts with the medial forebrain bundle to converge in the anterior internal capsule and medial prefrontal cortex. It might influence the regulation of mood through a reward–punishment circuit and dynamic equilibrium between positive and negative affective states, according to Coenen et al. (Reference Coenen, Panksepp, Hurwitz, Urbach and Madler2012), which suggests that the ATR might regulate the pathogenesis of depression through the reward and affective systems.
The CC is another important structure for the pathophysiology of MDD. Dalby et al. (Reference Dalby, Chakravarty, Ahdidan, Sorensen, Frandsen, Jonsdottir, Tehrani, Rosenberg, Ostergaard and Videbech2010a ) found more WM lesions in the CC of MDD patients, which might influence the ability to control cognition and emotion. A study of WM integrity in MDD also showed that depression might be associated with decreased FA values in the CC and SLF. Moreover, FA values were negatively correlated with symptom severity, especially in the CC (Cole et al. Reference Cole, Chaddock, Farmer, Aitchison, Simmons, McGuffin and Fu2012). Frodl et al. (Reference Frodl, Carballedo, Fagan, Lisiecka, Ferguson and Meaney2012) also reported that the high-risk group for MDD might have increased FA values in the SLF and CC, which might represent vulnerable characteristics for the formation of depression. A meta-analysis has also shown that the disturbances in inter-hemispheric connections of the CC might play a role in the pathophysiology of MDD (Liao et al. Reference Liao, Huang, Wu, Yang, Kuang, Du, Lui, Yue, Chan, Kemp and Gong2013). The above studies all support a possible marker in the CC for depression.
Apart from FA, radial diffusivity (RD) and axial diffusivity (AD) are also important parameters for WM structural integrity. RD and AD have been investigated in several studies of depression and could provide additional information for the underlying mechanisms of alterations in FA (Korgaonkar et al. Reference Korgaonkar, Grieve, Koslow, Gabrieli, Gordon and Williams2011; Mettenburg et al. Reference Mettenburg, Benzinger, Shimony, Snyder and Sheline2012; Aghajani et al. Reference Aghajani, Veer, van Lang, Meens, van den Bulk, Rombouts, Vermeiren and van der Wee2013; Charlton et al. Reference Charlton, Lamar, Zhang, Yang, Ajilore and Kumar2013).
Given that the majority of diffusion tensor imaging (DTI) studies to date in MDD have been performed on older-age subjects, we planned to enrol younger adults with first-episode medication-naive MDD in this study. From the above literature, we hypothesise that MDD patients might have alterations in the WM integrity of the CC, SLF and ATR, which connect the ‘limbic-cortico-striato-pallido-thalamic’ circuit to form the symptoms of depression. Moreover, depression severity and illness duration of MDD might be negatively correlated with FA values in the CC, SLF or ATR.
Method
Participants
The selection criteria for patients were as follows: (1) first-episode patients with a pure MDD diagnosis – Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria – made by the Structured Clinical Interview for DSM-IV; (2) no co-morbid psychiatric illnesses or medical illnesses; (3) severity of MDD was at least moderate: Clinician Global Impression of Severity > 4, Hamilton Rating Scale for Depression (HAMD) score > 20, Hamilton Rating Scale for Anxiety score < 5; (4) no previous cognitive behavioural therapy or other psychotherapies; (5) medication-naive; (6) no abuse of or dependence on alcohol or other substances; and (7) no past history of claustrophobia or discomfort while receiving magnetic resonance imaging (MRI) scanning. The healthy controls had no psychiatric illnesses or significant medical illnesses. All of the participants signed the informed consent that was approved by the Institutional Review Board, Buddhist Tzu Chi Hospital, Taipei Branch. At the time of the MRI, none of the participants in the control group received psychotropic treatment. Handedness was determined by using the Edinburgh Inventory of Handedness (Oldfield, Reference Oldfield1971).
MRI procedure: data acquisition
Structural MRI scans of brain were obtained with a 3 T Siemens (Siemens Medical Solutions, Germany) scanner housed at the MRI Center, National Yang Ming University. A single-shot, twice-refocused, spin-echo echo planar imaging pulse sequence DTI with 30 diffusion-sensitized gradient directions with the following parameters was performed (repetition time = 7900 ms; echo time = 79 ms; number of excitations = 3; directions = 30; number of acquisitions in axial orientation = 70; field of view = 256 mm × 256 mm; slice thickness = 2 mm; matrix = 128 × 128; b-value = 0 and 900 s/mm2) at the first visit. One non-diffusion-weighted (b0) image was also acquired.
DTI analysis
DTI analysis was performed using FMRIB's Diffusion Toolbox (FDT) function v. 2.0 [developed by the Oxford Centre for Functional MRI of the Brain (FMRIB), UK] that was implemented in FSL (FMRIB Software Library) (Smith et al. Reference Smith, Jenkinson, Woolrich, Beckmann, Behrens, Johansen-Berg, Bannister, De Luca, Drobnjak, Flitney, Niazy, Saunders, Vickers, Zhang, De Stefano, Brady and Matthews2004; Woolrich et al. Reference Woolrich, Jbabdi, Patenaude, Chappell, Makni, Behrens, Beckmann, Jenkinson and Smith2009). The merged DTI images were pre-processed by the step of eddy current correction to reduce the stretches and shears in diffusion-weighted images, to correct the motion between images and to adjust the gradient directions for rotations (Jenkinson & Smith, Reference Jenkinson and Smith2001). We also used a brain extraction tool (Smith, Reference Smith2002) to remove the non-brain tissue of the b0 image to obtain the nodif brain mask for the following DTIFIT process in FSL to fit a diffusion tensor model at each voxel. FA, eigenvector and eigenvalue maps were computed by the above procedure with the b vector and b value of gradient directions. Moreover, RD and AD maps were obtained by this step.
FA images were visually inspected for orientation and image quality. Then, the FA volumes were skeletonized and transformed into common space (Smith et al. Reference Smith, Johansen-Berg, Jenkinson, Rueckert, Nichols, Miller, Robson, Jones, Klein, Bartsch and Behrens2007), and all of the FA volumes were warped to the template by FMRIB's non-linear image registration. The mean FA volume of all of the individuals was thinned to create a mean FA skeleton that represented the centres of all of the WM tracts and provided the background WM tract map for the presentations of the TBSS (Tract-Based Spatial Statistics) results. The mean FA skeleton was thresholded and binarized at 0.2. Individual FA values were warped onto the mean FA skeleton.
Statistical analysis
For the demographic and clinical data, such as age, educational years and HAMD scores, the differences between patients and controls were estimated by the Mann–Whitney U test. Group differences of gender were analysed by a χ 2 test. For the DTI images, we performed the voxelwise analyses for the FA skeletons using non-parametric permutation-based inference as implemented in the FSL toolbox as a randomized function [with global brain volume determined by Structural Image Evaluation, using Normalisation, of the Atrophy (SIENAX) function of FSL), age and gender as covariates]. The analyses were based on the ‘whole-brain’ style, not traditional ‘region-of-interest’ style. This approach was expected to help us to avoid the possible biases from the hypothesis-driven region-of-interest approach. We set six contrasts, one for ‘control > patient’ and one for ‘patient > control’, in the FA statistical analysis of the WM tract. For RD and AD, there were four contrasts, for ‘control > patient’ and ‘patient > control’, in the RD and AD maps. Statistical p-maps were thresholded at p < 0.05 and were corrected for multiple comparisons across space [family-wise error (FWE) corrected]. In addition, we examined the extent to which FA was associated with the clinical variables (e.g. depression severity, anxiety severity, illness duration) and demographic variables (age, gender) that were used as covariates in the main analyses in each group and across both groups. For the statistical threshold of the correlations, we also used the corrected p < 0.05. The non-parametric permutations of group differences were labelled as red–yellow colours.
Results
Demographic data
We enrolled 44 patients with MDD and 27 controls. There were no significant differences in age, gender, education years or handedness. However, significant differences in HAMD scores were observed between the two groups (Table 1).
Demographic data of patients with major depressive disorder and control participants
Data are given as mean (standard deviation).
df, Degrees of freedom; n.a., not applicable; HAMD, Hamilton Rating Scale for Depression; HAMA, Hamilton Rating Scale for Anxiety.
a From Mann–Whitney U test for non-parametric independent two-sample t test.
WM integrity differences between patients and controls
We found that patients with MDD had lower FA values than controls in the left SLF and right ATR. Moreover, patients had higher RD values than controls in the bilateral SLF. The patient group also had lower AD values in the bilateral ATR (FWE corrected p < 0.05; Fig. 1 and Table 2). Moreover, the scores of HAMD were negatively correlated with FA values of the left SLF. Last, illness duration was also negatively associated with FA values of the right SLF and right ATR (FWE corrected p < 0.05; Fig. 1). All of the significant correlations were observed only in the patient group. Anxiety severity was not associated with FA values in the patient group. No significant correlations between the clinical variables and FA values were observed in the control group or across both groups. Montreal Neurological Institute (MNI) coordinates of peak regions of each significant cluster are also shown in Table 2. Even at a more lenient statistical threshold (p < 0.01 uncorrected), no significant alterations in FA, RD and AD were observed in the CC of the patient group.
Alterations in white matter (WM) fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF) and right anterior thalamic radiation (ATR) of patients with major depressive disorder (a). A negative correlation was observed between Hamilton Rating Scale for Depression scores and WM FA in the SLF (b). A negative correlation was observed between illness duration and WM FA in the right ATR and SLF (c). Alterations in WM radial diffusivity in the bilateral SLF (d) and alterations in WM axial diffusivity in the bilateral ATR (e). L, Left; R, right.
WM tract clusters of significant FA, RD and AD differences between healthy controls and patients
WM, white matter; FA, fractional anisotropy; RD, radial diffusivity; AD, axial diffusivity; MNI, Montreal Neurological Institute; SLF, superior longitudinal fasciculus; ATR, anterior thalamic radiation.
Discussion
In the present study, we found that younger adult patients with MDD had impairments in WM integrity of the left SLF and right ATR. Moreover, higher RD values in the bilateral SLF and lower AD values in the bilateral ATR were observed. This finding might explain that a reduction in FA of the left SLF and right ATR might be partly due to decreases in longitudinal diffusivity of the ATR and increases in RD of the SLF (Aghajani et al. Reference Aghajani, Veer, van Lang, Meens, van den Bulk, Rombouts, Vermeiren and van der Wee2013). This finding also suggests that a pattern of demyelination or another degeneration process in the SLF and ATR could occur in young adult patients with MDD (Korgaonkar et al. Reference Korgaonkar, Grieve, Koslow, Gabrieli, Gordon and Williams2011). FA values of the left SLF were negatively correlated with depression severity and illness duration. The innovative strength of our study included that most of the enrolled patients were young adults compared with previous studies, which mostly were conducted on older-aged patients (Taylor et al. Reference Taylor, MacFall, Gerig and Krishnan2007; Dalby et al. Reference Dalby, Frandsen, Chakravarty, Ahdidan, Sorensen, Rosenberg, Videbech and Ostergaard2010b ; Steffens et al. Reference Steffens, Taylor, Denny, Bergman and Wang2011; Sexton et al. Reference Sexton, Le Masurier, Allan, Jenkinson, McDermott, Kalu, Herrmann, Bradley, Mackay and Ebmeier2012; Charlton et al. Reference Charlton, Lamar, Zhang, Yang, Ajilore and Kumar2013; McIntosh et al. Reference McIntosh, Bastin, Luciano, Maniega, Del C Valdés Hernández, Royle, Hall, Murray, Lawrie, Starr, Wardlaw and Deary2013). Moreover, our patients were first-episode and medication-naive, not treatment-resistant or chronic patients with MDD. Our results could have different clinical implications compared with other studies of treatment-resistant patients (Guo et al. Reference Guo, Liu, Chen, Xu, Wu, Ma, Gao, Tan, Sun, Xiao, Chen and Zhao2012; de Diego-Adeliño et al. Reference de Diego-Adeliño, Pires, Gómez-Ansón, Serra-Blasco, Vives-Gilabert, Puigdemont, Martín-Blanco, Alvarez, Pérez and Portella2013; Peng et al. Reference Peng, Zheng, Ning, Zhang, Shan, Zhang, Yang, Liu, Li, Zhou, Zhang and Li2013) and chronic patients (Guo et al. Reference Guo, Liu, Chen, Xu, Wu, Ma, Gao, Tan, Sun, Xiao, Chen and Zhao2012; de Diego-Adeliño et al. Reference de Diego-Adeliño, Pires, Gómez-Ansón, Serra-Blasco, Vives-Gilabert, Puigdemont, Martín-Blanco, Alvarez, Pérez and Portella2013; Peng et al. Reference Peng, Zheng, Ning, Zhang, Shan, Zhang, Yang, Liu, Li, Zhou, Zhang and Li2013). However, the method used in the current study did not have the ability to resolve the crossing fibre issue (Frodl et al. Reference Frodl, Carballedo, Fagan, Lisiecka, Ferguson and Meaney2012) of DTI analysis. In addition, our study did not use the quantitative tractography technique to calculate the normalized number of fibres (Zhang et al. Reference Zhang, Leow, Ajilore, Lamar, Yang, Joseph, Medina, Zhan and Kumar2012). Our study results were also not confirmed by tractography that was performed in the other studies (Gutman et al. Reference Gutman, Holtzheimer, Behrens, Johansen-Berg and Mayberg2009; Dalby et al. Reference Dalby, Frandsen, Chakravarty, Ahdidan, Sorensen, Rosenberg, Videbech and Ostergaard2010b ; Frodl et al. Reference Frodl, Carballedo, Fagan, Lisiecka, Ferguson and Meaney2012; Zhang et al. Reference Zhang, Leow, Ajilore, Lamar, Yang, Joseph, Medina, Zhan and Kumar2012).
The findings of lower FA values in the SLF replicated the results of several previous studies of depression. Dalby et al. (Reference Dalby, Frandsen, Chakravarty, Ahdidan, Sorensen, Rosenberg, Videbech and Ostergaard2010b ) reported that more WM lesions in the SLF (lower FA values) were associated with more severe MDD symptoms. Widespread WM deficits in the SLF have also been reported in MDD patients (Cole et al. Reference Cole, Chaddock, Farmer, Aitchison, Simmons, McGuffin and Fu2012). A meta-analysis study showed that impairments in WM integrity of the SLF were a very stable biomarker in the pathophysiology of MDD (Murphy & Frodl, Reference Murphy and Frodl2011). The SLF is involved in the modulation of cognitive and emotional functions. Vestergaard et al. (Reference Vestergaard, Madsen, Baare, Skimminge, Ejersbo, Ramsoy, Gerlach, Akeson, Paulson and Jernigan2011) found that better working memory performance was correlated with increased FA values in the SLF. The sensitivity and sustained ability of attention are also correlated with WM micro-integrity in the SLF (Klarborg et al. Reference Klarborg, Skak Madsen, Vestergaard, Skimminge, Jernigan and Baaré2012). Biesbroek et al. (Reference Biesbroek, Kuijf, van der Graaf, Vincken, Postma, Mali, Biessels and Geerlings2013) found that the volume of lacunar lesion in the SLF was also correlated with impairments in executive function. Niida et al. (Reference Niida, Niida, Kuniyoshi, Motomura and Uechi2013) proposed that FA values of the left SLF combined with a visual evaluation of the ATR might be a useful auxiliary diagnostic tool for depression. Imaging genetics have also shown that dysfunctional WM changes in the SLF are associated with a catechol-O-methyltransferase polymorphism in MDD (Seok et al. Reference Seok, Choi, Lim, Lee, Kim and Ham2013). Our results on decreased WM micro-integrity in the SLF might suggest that MDD patients have significant impairments in cognitive and emotional functions, which might be attributed to the structural abnormality in the connecting characteristics between the frontal and parietal lobes of the SLF in MDD. The impairments in WM FA of the SLF also correspond to the ‘cortico-limbic-striato-pallido-thalamic’ circuit hypothesis of MDD (Sheline, Reference Sheline2000), which involves a disturbance in the connections between cortical structures, such as the frontal and parietal lobes.
The ATR connects the thalamus with the prefrontal cortex and occipital cortex. It could control the expression of emotions (Spalletta et al. Reference Spalletta, Fagioli, Caltagirone and Piras2012). Abnormalities in the ATR might contribute to distortions of the cognitive, affective and reward functions (Mamah et al. Reference Mamah, Conturo, Harms, Akbudak, Wang, McMichael, Gado, Barch and Csernansky2010; Coenen et al. Reference Coenen, Panksepp, Hurwitz, Urbach and Madler2012). A study of MDD showed that WM micro-structural abnormalities in the SLF and ATR might represent a WM biomarker for the aetiology of MDD (Sexton et al. Reference Sexton, Le Masurier, Allan, Jenkinson, McDermott, Kalu, Herrmann, Bradley, Mackay and Ebmeier2012), which also corresponds with our results. WM micro-structural integrity in the ATR and SLF could be related to cognitive and executive function (Biesbroek et al. Reference Biesbroek, Kuijf, van der Graaf, Vincken, Postma, Mali, Biessels and Geerlings2013). Apart from the cognitive domain, structural abnormalities in the ATR could disturb the dynamic equilibrium between the positive and negative affective states in MDD (Coenen et al. Reference Coenen, Panksepp, Hurwitz, Urbach and Madler2012). Moreover, alterations in WM micro-integrity of the ATR can be compatible with the theory of having a ‘cortico-limbic-striato-pallido-thalamic’ circuit for MDD. From the above literature, we can conclude that the ATR and SLF could represent specific abnormalities in the WM circuit for young adult patients with first-episode medication-naive MDD, which appears to be different from the results of the older-aged patient group (Taylor et al. Reference Taylor, MacFall, Gerig and Krishnan2007; Dalby et al. Reference Dalby, Frandsen, Chakravarty, Ahdidan, Sorensen, Rosenberg, Videbech and Ostergaard2010b ; Steffens et al. Reference Steffens, Taylor, Denny, Bergman and Wang2011; Sexton et al. Reference Sexton, Le Masurier, Allan, Jenkinson, McDermott, Kalu, Herrmann, Bradley, Mackay and Ebmeier2012; Charlton et al. Reference Charlton, Lamar, Zhang, Yang, Ajilore and Kumar2013; McIntosh et al. Reference McIntosh, Bastin, Luciano, Maniega, Del C Valdés Hernández, Royle, Hall, Murray, Lawrie, Starr, Wardlaw and Deary2013). This finding could be an important strength of our study and could represent a biomarker for MDD in first-episode, medication-naive and young adults.
Our study had less impact from ageing, medication and chronicity, which makes the strengths totally different from previous studies, which had the limitations of using only older-age patients in late-onset depression, which might represent a different subtype with respect to MDD (Taylor et al. Reference Taylor, MacFall, Gerig and Krishnan2007; Dalby et al. Reference Dalby, Frandsen, Chakravarty, Ahdidan, Sorensen, Rosenberg, Videbech and Ostergaard2010b ; Steffens et al. Reference Steffens, Taylor, Denny, Bergman and Wang2011; Sexton et al. Reference Sexton, Le Masurier, Allan, Jenkinson, McDermott, Kalu, Herrmann, Bradley, Mackay and Ebmeier2012; Charlton et al. Reference Charlton, Lamar, Zhang, Yang, Ajilore and Kumar2013; McIntosh et al. Reference McIntosh, Bastin, Luciano, Maniega, Del C Valdés Hernández, Royle, Hall, Murray, Lawrie, Starr, Wardlaw and Deary2013).
The present study did not replicate the findings on WM fibre tracts other than the ATR and SLF, such as the uncinate fasciculus (Versace et al. Reference Versace, Almeida, Quevedo, Thompson, Terwilliger, Hassel, Kupfer and Phillips2010; Steffens et al. Reference Steffens, Taylor, Denny, Bergman and Wang2011; Murphy et al. Reference Murphy, Carballedo, Fagan, Morris, Fahey, Meaney and Frodl2012; Zhang et al. Reference Zhang, Leow, Ajilore, Lamar, Yang, Joseph, Medina, Zhan and Kumar2012; McIntosh et al. Reference McIntosh, Bastin, Luciano, Maniega, Del C Valdés Hernández, Royle, Hall, Murray, Lawrie, Starr, Wardlaw and Deary2013) or the CC (Dalby et al. Reference Dalby, Chakravarty, Ahdidan, Sorensen, Frandsen, Jonsdottir, Tehrani, Rosenberg, Ostergaard and Videbech2010a ; Cole et al. Reference Cole, Chaddock, Farmer, Aitchison, Simmons, McGuffin and Fu2012; Frodl et al. Reference Frodl, Carballedo, Fagan, Lisiecka, Ferguson and Meaney2012; Huang et al. Reference Huang, Gundapuneedi and Rao2012; Liao et al. Reference Liao, Huang, Wu, Yang, Kuang, Du, Lui, Yue, Chan, Kemp and Gong2013). A possible explanation is that our patients with MDD might have almost no medication effects due to medication-naive characteristics and less impact from a chronic illness course due to having first-episode characteristics. Therefore, our patients might not have significant structural alterations of the uncinated fasciculus or CC. As is known, the uncinate fasciculus connects the hippocampus with the frontal cortex, which could be impaired in long-term illness. The CC connects bilateral hemispheres, which could also be affected after a chronic illness course. However, more longitudinal study is needed to explore the course of alteration in WM micro-integrity for MDD. Moreover, the previous positive results of the ATR and SLF mostly appear to be obtained from late-onset MDD patients. However, previous studies could not completely exclude the biases from medication and episodes of chronicity. Our ATR and SLF results, nevertheless, had some clinical meaning for resolving the aetiology of WM micro-integrity in MDD.
Limitations
Our study had several limitations. First, the cross-sectional design, limited sample size and lack of further tractography might limit the interpretations of our results. Second, DTI is still a non-specific measure that does not provide information about the underlying causes for the reported micro-structural pathology. However, some strength would definitely be added to the study if other measures of WM integrity, such as AD, RD and mean diffusivity, were also examined. Third, detailed histopathological validation of FA in healthy humans is still missing, which might bias our findings. However, animal studies have shown that diffusivity is related to WM integrity in histopathology (Song et al. Reference Song, Yoshino, Le, Lin, Sun, Cross and Armstrong2005). Fourth, the lack of power and limited directional resolution of the suboptimal DTI protocol (30 directions) in this study could be associated with the limited number of structures involved. Fifth, the later-on bipolar disorder diagnosis of first-episode MDD could be a possible bias for our study. Last, the current DTI method does not make it possible to disentangle the WM tract of the crossing fibres to a high certainty in the brain, and our study results were not confirmed by tractography.
Conclusions
From the study results, we conclude that significant alterations in WM micro-integrity of the left SLF and right ATR might be possible WM biomarkers for young adult patients with MDD.
Acknowledgements
We thank Mr Y. F. Chen for transportation help, Ms. Wang (MRI Center, National Yang Ming University) for help with MRI acquisition and the Buddhist Tzu-Chi General Hospital, Taipei Branch hospital for grant support (project no. TCRD-TPE-100-02). We also acknowledge MR support from the National Yang-Ming University, Taiwan, which is in part supported by the MOE plan for the top university.
Declaration of Interest
None.
