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This study aimed to investigate alterations in white matter (WM) microstructure in patients with psychotic and non-psychotic bipolar disorder (PBD and NPBD, respectively). We used 3T-magnetic resonance imaging to examine 29 PBD, 23 NPBD, and 65 healthy control (HC) subjects. Using tract-based spatial statistics for diffusion tensor imaging data, we compared fractional anisotropy (FA) and mean diffusion (MD) pairwise among the PBD, NPBD, and HC groups. We found several WM areas of decreased FA or increased MD in the PBD and NPBD groups compared to HC. PBD showed widespread FA decreases in the corpus callosum as well as the bilateral internal capsule and fornix. However, NPBD showed local FA decreases in a part of the corpus callosum body as well as in limited regions within the left cerebral hemisphere, including the anterior and posterior corona radiata and the cingulum. In addition, both PBD and NPBD shared widespread MD increases across the posterior corona radiata, cingulum, and sagittal stratum. These findings suggest that widespread WM microstructural alterations might be a common neuroanatomical characteristic of bipolar disorder, regardless of being psychotic or non-psychotic. Particularly, PBD might involve extensive inter-and intra-hemispheric WM connectivity disruptions., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to investigate abnormalities in the gray matter and white matter (GM and WM, respectively) that are shared between schizophrenia (SZ) and bipolar disorder (BD). We used 3T-magnetic resonance imaging to examine patients with SZ, BD, or healthy control (HC) subjects (aged 20-50 years, N = 65 in each group). We generated modulated GM maps through voxel-based morphometry (VBM) for T1-weighted images and skeletonized fractional anisotropy, mean diffusion, and radial diffusivity maps through tract-based special statistics (TBSS) methods for diffusion tensor imaging (DTI) data. These data were analyzed using a generalized linear model with pairwise comparisons between groups with a family-wise error corrected P < 0.017. The VBM analysis revealed widespread decreases in GM volume in SZ compared to HC, but patients with BD showed GM volume deficits limited to the right thalamus and left insular lobe. The TBSS analysis showed alterations of DTI parameters in widespread WM tracts both in SZ and BD patients compared to HC. The two disorders had WM alterations in the corpus callosum, superior longitudinal fasciculus, internal capsule, external capsule, posterior thalamic radiation, and fornix. However, we observed no differences in GM volume or WM integrity between SZ and BD. The study results suggest that GM volume deficits in the thalamus and insular lobe along with widespread disruptions of WM integrity might be the common neural mechanisms underlying the pathologies of SZ and BD., Competing Interests: The authors have declared that no competing interests exist.

Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the 'mirror neuron system', including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.

It has been proposed that positive emotional biases could make bipolar manic (BM) patients maintain abnormally approaching behaviors during social interactions. To test this hypothesis, we measured interpersonal distance (IPD) and gaze angle of BM patients and normal controls (NCs) during social interaction in immersive virtual environment. Overall, IPDs of BM patients (n = 20) were greater than those of normal controls (n = 20). The IPD difference was even greater between NCs and BM patients with psychotic features (n = 11) than those without psychotic features (n = 9). Regardless of the presence of psychotic features, BM patients averted their gazes more than NCs, and even more while speaking than while listening. Our results might suggest negativistic social cognition of bipolar patients, as was previously found even during a manic phase, or the role of paranoid symptoms in avoidant social behaviors, in agreement with prior studies with schizophrenic patients. Use of proper space and gaze might have psychotherapeutic implication in developing secure, two-person relationship with bipolar patients regardless of the presence of disrupting manic symptoms.