br Introduction Major depressive disorder MDD and bipolar di

Introduction Major depressive disorder (MDD) and bipolar disorder (BD) are two major types of mood disorder. Although mania or hypomania is a defining feature of BD patients, the presence of subthreshold manic symptoms can be observed in both disorders during a depressive episode (de Almeida & Phillips, 2013). This leads to difficulty in distinguishing BD from MDD patients as they have the same diagnostic criteria for a depressive episode (Phillips & Kupfer, 2013). Actually, misdiagnosing BD as MDD has many potentially deleterious consequences because treatment with antidepressants in the absence of a mood stabilizer carries the risk of precipitating mania and may increase rates of cycling between mood states (Baldessarini et al., 2010). In fact, whether MDD and BD have different neural mechanisms or share some in common remains ambiguous (de Almeida & Phillips, 2013; McGuffin et al., 2003). Neuroimaging studies have identified a number of differences between patients with depressive disorders and healthy controls in AZD 0530 structure and function. Until now, it is still unclear to what extent specific or common morphological alterations occur in MDD and BD given the paucity of direct comparisons. Based on brain structural images, brain morphologic characteristics have been studied in various brain diseases (de Vos et al., 2016; van Lutterveld et al., 2014). Using the voxel-based morphometry (VBM) method, some studies detected altered brain GM volume or density in patients with MDD or BD (Redlich et al., 2014) and found between-group difference in GM volume primarily in the prefrontal cortex (PFC), anterior cingulate gyrus (ACG), amygdala, and hippocampus (Redlich et al., 2014; Koutsouleris et al., 2015). Actually, the VBM method is susceptible to several potential confounds, including the accuracy of the brain segmentation, degree of smoothing, strategies used in registration, and the choice of a normalization template (Bookstein, 2001). Especially, VBM analysis is a method of measuring MRI signal alteration in brain tissue rather than a directly technique to detect brain structural alteration about the volume size of a region, CT and cortical surface area (Bookstein, 2001). CT analysis is similar to VBM, albeit the analysis is performed at the nodes of a 3D polygonal mesh rather than on a 3D voxel grid. And the CT analysis has the advantage of providing a direct quantitative index (in unit of mm), rather than qualitative index, of cortical morphology. Therefore, the measurement of CT alteration has been suggested as a way to obtain a complementary indication of alterations in brain GM morphology (Ecker et al., 2013). For depressive disorders, previous studies focused primarily on CT alteration in just one of the depressive disorders, comparing the patients with healthy controls (Redlich et al., 2014; Maller et al., 2014), but ignoring the abnormal CT between the two disorders. Several studies of BD patients reported subtle but widespread CT abnormalities and showed decreased CT in the left anterior cingulate/paracingulate, left superior temporal gyrus and prefrontal regions (Rimol et al., 2010, 2012; Hanford et al., 2016). And several studies of MDD patients reported reduced CT in the medial orbitofrontal gyrus and pars opercularis (van Eijndhoven et al., 2013; Tu et al., 2012), and a study reported increased CT in similar regions (Qiu et al., 2014). By now, very few studies have directly compared the difference in brain CT between MDD and BD patients (Lan et al., 2014; Fung et al., 2015), and those that did obtained partially inconsistent results. For example, Lan et al. (2014) investigated the difference in CT between 18 BD patients and 56 MDD patients and reported thinner CT in the right caudal middle frontal cortex, left inferior parietal cortex, and right precuneus in a mixed group of BD-I and BD-II patients. However, Fung et al. (2015) failed to find any brain regions with differences in CT between MDD and BD patients. Notably, in these two studies, the analyses were performed on patients who were taking medications, which may have influenced the results.