Delayed diagnosis of bipolar disorder (BD) is common. However, diagnostic validity may be enhanced using reliable neurobiological markers for BD. Degree centrality (DC) is one such potential marker that enables researchers to visualize neuronal network abnormalities in the early stages of some neuropsychiatric disorders. In the present study, we measured resting-state DC abnormalities and cognitive deficits in order to identify early neurobiological markers for BD. We recruited 23 patients with BD who had recently experienced manic episodes (duration of illness <2 years) and 46 matched healthy controls. Our findings indicated that patients with BD exhibited DC abnormalities in frontal areas, temporal areas, the right postcentral gyrus, and the posterior lobe of the cerebellum. Moreover, correlation analysis revealed that psychomotor speed indicators were associated with DC in the superior temporal and inferior temporal gyri, while attention indicators were associated with DC in the inferior temporal gyrus, in patients with early BD. Our findings suggest that DC abnormalities in neural emotion regulation circuits are present in patients with early BD, and that correlations between attention/psychomotor speed deficits and temporal DC abnormalities may represent early markers of BD.

Background Bipolar I disorder (BD‐I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting‐state functional magnetic resonance imaging (rs‐fMRI) allows non‐invasive mapping of brain functional connectivity. The current study used an unbiased voxel‐based graph theory analysis of rs‐fMRI to investigate the intrinsic brain networks of BD‐I patients with and without suicide attempt. Methods A total of 30 BD‐I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non‐attempter group), and 67 healthy controls underwent rs‐fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. Results Compared with the non‐attempter group, we found regional differences in GBC values in emotion‐encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub‐like regions displayed fair to good power in distinguishing attempters from non‐attempters among BD‐I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. Conclusions Our results indicate that abnormal connectivity patterns in emotion‐encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion‐encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

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Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, −20.0; 160 mg, −19.9) vs. placebo (−14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.

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