The present study investigated functional connectivity and white matter integrity of the fronto-parietal network (FPN) to reveal the neural mechanisms that underlie late-life depression (LLD). Fifty patients with LLD and 40 non-depressed controls were included in the study. A multi-parametric approach was used by applying independent component analysis (ICA) to estimate functional connectivity of the FPN and by applying tract-based spatial statistics to examine white-matter integrity in tracts to the FPN. Patients with LLD exhibited functional abnormalities in the right inferior frontal gyrus, middle frontal gyrus, and inferior parietal gyrus and lower white matter fractional anisotropy in the right inferior fronto-occipital fasciculus, anterior thalamic radiation, and uncinate fasciculus. Alterations of functional connectivity and white matter fractional anisotropy in these regions were negatively correlated with the severity of symptomatic anxiety in LLD patients. The right inferior frontal gyrus might be a crucial hub in transferring information between these abnormal regions. Significant correlations were found between anxiety symptoms and brain alterations, suggesting that impairments in the FPN network might be involved in symptomatic anxiety in elderly individuals with depression.

Background: Subclinical anxiety, depressive and somatic symptoms appear closely related. However, it remains unclear whether somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and what the underlying neuroimaging mechanisms are for the mediating effect. Methods: Data of healthy participants (n = 466) and participants in remission of major depressive disorder (n = 53) were obtained from the Human Connectome Project. The Achenbach Adult Self-Report was adopted to assess anxiety, depressive and somatic symptoms. All participants completed four runs of resting-state functional magnetic resonance imaging. Mediation analyses were utilized to explore the interactions among these symptoms and their neuroimaging mechanisms. Results: Somatic symptoms partially mediated the association between subclinical anxiety and depressive symptoms in healthy participants (anxiety→somatic→depression: effect: 0.2785, Boot 95% CI: 0.0958–0.3729; depression→somatic→anxiety: effect: 0.0753, Boot 95% CI: 0.0232–0.1314) and participants in remission of MDD (anxiety→somatic→depression: effect: 0.2948, Boot 95% CI: 0.0357–0.7382; depression→somatic→anxiety: effect: 0.0984, Boot 95% CI: 0.0007–0.2438). Resting-state functional connectivity (FC) between the right medial superior frontal gyrus and the left thalamus and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in healthy participants (effect: 0.0020, Boot 95% CI: 0.0003–0.0043). The mean strength of common FCs of subclinical depressive and somatic symptoms, somatic symptoms, and the mean strength of common FCs of subclinical anxiety and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in remission of MDD (effect: 0.0437, Boot 95% CI: 0.0024–0.1190). These common FCs mainly involved the insula, precentral gyri, postcentral gyri and cingulate gyri. Furthermore, FC between the triangular part of the left inferior frontal gyrus and the left postcentral gyrus was positively associated with subclinical anxiety, depressive and somatic symptoms in remission of MDD (FDR-corrected p < 0.01). Conclusions: Somatic symptoms partially mediate the interaction between subclinical anxiety and depressive symptoms. FCs involving the right medial superior frontal gyrus, left thalamus, triangular part of left inferior frontal gyrus, bilateral insula, precentral gyri, postcentral gyri and cingulate gyri maybe underlie the mediating effect of somatic symptoms.

Perceived stress impairs cognitive function across the adult lifespan, but the extent to which cognition decline is variable across individuals. Individual differences in the stress response are described as personality traits. Substantial individual differences in the magnitude of cognitive impairment that is induced by short-term perceived stress are poorly understood. The present study tested the hypothesis that the relationship between short-term perceived stress and different aspects of cognition is mediated by personality traits. The study included 1066 participants with behavior and neuroimaging data from the Human Connectome Project after excluding individuals with missing variables. In the result, the parallel multiple mediation model demonstrated that the influence of perceived stress on the total and crystalized cognition is mainly mediated by neuroticism (indirect effect = −0.04, p < 0.05) and conscientiousness (indirect effect = 0.05, p < 0.05) in adults. Cortical thickness value (n = 1066) of the right superior frontal gyrus (SFG) showed not only positive correlations with short-term perceived stress and neuroticism, but negative associations with cognition. The chain mediation model found that the right SFG and neuroticism play a small but significant chain mediating effect between stress and total cognition. The strength of the resting-state functional connectivity (n = 968) between the left orbitofrontal cortex versus the left superior medial frontal cortex was positively correlated with crystallized cognition and negatively associated with conscientiousness. These results extend previous findings by the impacts of short-term perceived stress on cognitive function is mediated by neuroticism and the right SFG was the underlying neural mechanism.

Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18–65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6. A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (−12.46; χ²=−9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group. Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.

Late-life depression (LLD) is an important public health problem among the aging population. Recent studies found that mindfulness-based cognitive therapy (MBCT) can effectively alleviate depressive symptoms in major depressive disorder. The present study explored the clinical effect and potential neuroimaging mechanism of MBCT in the treatment of LLD. We enrolled 60 participants with LLD in an 8-week, randomized, controlled trial (ChiCTR1800017725). Patients were randomized to the treatment-as-usual (TAU) group or a MBCT+TAU group. The Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluate symptoms. Magnetic resonance imaging (MRI) was used to measure changes in resting-state functional connectivity and structural connectivity. We also measured the relationship between changes in brain connectivity and improvements in clinical symptoms. HAMD total scores in the MBCT+TAU group were significantly lower than in the TAU group after 8 weeks of treatment (p < 0.001) and at the end of the 3-month follow-up (p < 0.001). The increase in functional connections between the amygdala and middle frontal gyrus (MFG) correlated with decreases in HAMA and HAMD scores in the MBCT+TAU group. Diffusion tensor imaging analyses showed that fractional anisotropy of the MFG-amygdala significantly increased in the MBCT+TAU group after 8-week treatment compared with the TAU group. Our study suggested that MBCT improves depression and anxiety symptoms that are associated with LLD. MBCT strengthened functional and structural connections between the amygdala and MFG, and this increase in communication correlated with improvements in clinical symptoms.Randomized Controlled Trial; Follow-Up Study; fMRI; Brain Connectivity