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Abstract: Objective: Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Methods: Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. Results: We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right middle frontal gyrus, the right dorsal anterior insular, the right cerebellum posterior gyrus, and the right posterior cingulate cortex showed abnormality specific to the UD group. Conclusions: We found brain regions showing resting state ReHo differences and examined their sensitivity and specificity, suggesting a potential neuroimaging biomarker to distinguish between BD-dep and UD patients. We further clarified the pathophysiological abnormality of these regions for each of the two patient populations. [Copyright &y& Elsevier]

Abstract: We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal–limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD. [Copyright &y& Elsevier]