Altered white matter integrity in first-episode, treatment-naive young adults with major depressive disorder: A tract-based spatial statistics study

A number of studies have shown an association between diabetes and depression. However, the underlying mechanisms are still unclear. Previous findings indicate a role for the prefrontal cortex and subcortical gray matter regions in type 2 diabetes and major depressive disorder (MDD). The purpose of this study was to examine the white matter integrity in the fibers that are part of the anterior limb of internal capsule (ALIC) in MDD and diabetic subjects using diffusion tensor imaging tractography. We studied 4 groups of subjects including 1) 42 healthy controls (HC), 2) 28 MDD subjects (MD), 3) 24 patients diagnosed with type 2 diabetes without depression (DC), and 4) 22 patients diagnosed with diabetes and depression (DD). Results revealed significantly decreased fractional anisotropy (FA; P ¼ .021) and a trend towards significant increase in radial diffusivity (RD; P ¼ .078) of the right ALIC in depressed subjects (MD þ DD) compared to non-depressed subjects (HC þ DC). While there were no significant diabetes effects or interactions between depression and diabetes, subjects with high depression ratings and high hemoglobin A1c levels had the lowest mean FA values in the right ALIC. In addition, we found a significant negative correlation between FA of the left ALIC with hemoglobin A1c in diabetic subjects (DC þ DD; P ¼ .016). Our study demonstrated novel findings of white matter abnormalities of the ALIC in depression and diabetes. These findings have implications for clinical manifestations of depression and diabetes as well as their pathophysiology.

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 97%

White Matter Tract Integrity of Anterior Limb of Internal Capsule in Major Depression and Type 2 Diabetes

Zhang

Ajilore

Zhan³

et al. 2013

“…In an effort to better understand the pathophysiology of MDD and develop more effective treatments, much research has focused on delineating the structure and function of this mood regulation network. Although many studies have focused on the function of the network (Drevets et al, 2008b;Hafeman et al, 2012;Mayberg, 2003a, b;Murray et al, 2011;Phillips, 2006), including functional connectivity between key brain regions (Craddock et al, , 2012Greicius, 2008Greicius, , 2007James et al, 2009;Seminowicz et al, 2004;Sheline et al, 2010), others have focused on the structural connectivity of the network, ie, the white matter (WM) pathways between brain regions (Abe et al, 2010;Blood et al, 2010;Cole et al, 2012;Cullen et al, 2010;Kieseppa et al, 2010;Korgaonkar et al, 2011;Ma et al, 2007;Tha et al, 2013;Wu et al, 2011;Zhu et al, 2011;Zou et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous DTI studies have looked for WM integrity differences in patients with MDD (Abe et al, 2010;Blood et al, 2010;Cole et al, 2012;Cullen et al, 2010;Kieseppa et al, 2010;Korgaonkar et al, 2011;Ma et al, 2007;Tha et al, 2013;Wu et al, 2011;Zhu et al, 2011;Zou et al, 2008). However, the findings have been highly variable with respect to the location and direction of the difference in FA (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

Choi

Holtzheimer

Franco

et al. 2013

Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n ¼ 134) and healthy controls (n ¼ 54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.

“…Fractional anisotropy (FA) quantifies the directionally preferential water molecule diffusivity, and is usually used to assess overall white matter integrity. Using voxel-or region-based analyses, several DTI studies have revealed frontal and temporal white matter abnormalities in late-life depression (Nobuhara et al, 2006;Shimony et al, 2009), as well as in non-geriatric MDD (Wu et al, 2011;Ma et al, 2007;Zhu et al, 2011). For example, lower FA has been reported in frontal, temporal, and parietal regions for first-episode, treatment-naive younger adults with MDD (Ma et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging

Zhang

Leow

Ajilore

et al. 2011

110

105

Previous findings suggested the role of the prefrontal cortex, hippocampus, and cingulate gyrus in major depressive disorders (MDD), but the white matter microstructural abnormalities of the fibers connecting these brain structures are not known. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF) and cingulum bundle (CB) among MDD subjects. A total of 21 MDD subjects aged between 30 and 65 years and 21 age-matched healthy controls (HC) were recruited. All subjects were right-handed and without history of diabetes or other cardiac diseases. We extracted quantitative tract-specific measures based on diffusion tensor imaging tractography to examine both diffusivity and geometric properties of the UF and CB. Significantly decreased fractional anisotropy (FA) and increased radial diffusivity of the right UF were observed in MDD patients compared with HC (po0.05), while their geometric characteristics remained relatively unchanged. Among MDD subjects, depression severity had a significant negative correlation with normalized number of fibers (NNF) in the right UF (r ¼ À0.53, p ¼ 0.02). We also found significant age effect (oldoyoung) in HC group and laterality effect (L4R) in both groups in the FA measure of the CB. Our study demonstrates novel findings of white matter microstructural abnormalities of the right UF in MDD. In the MDD group, the severity of depression is associated with reduced NNF in the right UF. These findings have implications for both clinical manifestations of depression as well as its pathophysiology.