Functional and structural alterations in different durations of untreated illness in the frontal and parietal lobe in major depressive disorder.

Major depressive disorder (MDD) is one of the most disabling illnesses that profoundly restricts psychosocial functions and impairs quality of life. However, the treatment rate of MDD is surprisingly low because the availability and acceptability of appropriate treatments are limited. Therefore, identifying whether and how treatment delay affects the brain and the initial time point of the alterations is imperative, but these changes have not been thoroughly explored. We investigated the functional and structural alterations of MDD for different durations of untreated illness (DUI) using regional homogeneity (ReHo) and voxel-based morphometry (VBM) with a sample of 125 treatment-naïve MDD patients and 100 healthy controls (HCs). The MDD patients were subgrouped based on the DUI, namely, DUI ≤ 1 M, 1 < DUI ≤ 6 M, 6 < DUI ≤ 12 M, and 12 < DUI ≤ 48 M. Subgroup comparison (MDD with different DUIs) was applied to compare ReHo and grey matter volume (GMV) extracted from clusters of regions with significant differences (the pooled MDD patients relative to HCs). Correlations and mediation effects were analysed to estimate the relationships between the functional and structural neuroimaging changes and clinical characteristics. MDD patients exhibited decreased ReHo in the left postcentral gyrus and precentral gyrus and reduced GMV in the left middle frontal gyrus and superior frontal gyrus relative to HCs. The initial functional abnormalities were detected after being untreated for 1 month, whereas this duration was 3 months for GMV reduction. Nevertheless, a transient increase in ReHo was observed after being untreated for 3 months. No significant differences were discovered between HCs and MDD patients with a DUI less than 1 month or among MDD patients with different DUIs in either ReHo or GMV. Longer DUI was related to reduced ReHo with GMV as mediator in MDD patients. We identified disassociated functional and anatomical alterations in treatment-naïve MDD patients at different time points in distinct brain regions at the early stage of the disease. Additionally, we also discovered that GMV mediated the relationship between a longer DUI and diminished ReHo in MDD patients, disclosing the latent deleterious and neuro-progressive implications of DUI on both the structure and function of the brain and indicating the necessity of early treatment of MDD.

Gray matter volume reduction in orbitofrontal cortex correlated with plasma glial cell line-derived neurotrophic factor (GDNF) levels within major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a severe mental disorder characterized by reduced gray matter volume (GMV). To date, the pathogenesis of MDD remains unclear, but neurotrophic factors play an essential role in the pathophysiological alterations of MDD during disease development. In particular, plasma glial cell line-derived neurotrophic factor (GDNF) has been suggested as a potential biomarker that may be associated with disease activity and neurological progression in MDD. Our study investigated whether plasma GDNF levels in MDD patients and healthy controls (HCs) are correlated with GMV alterations. METHODS: We studied 54 MDD patients and 48 HCs. The effect of different diagnoses on whole-brain GMV was investigated using ANOVA (Analysis of Variance). The threshold of significance was p < 0.05, and Gaussian random-field (GRF) correction for error was used. All analyses were controlled for covariates such as ethnicity, handedness, age, and gender that could affect GMV. RESULT: Compared with the HC group, the GMV in the MDD group was significantly reduced in the right inferior orbitofrontal cortex (OFC), and plasma GDNF levels were significantly higher in the MDD group than in the HC group. In the right inferior OFC, the GDNF levels were positively correlated with GMV reduction in the MDD group, whereas in the HC group, a negative correlation was observed between GDNF levels and GMV reduction. CONCLUSION: Although increased production of GDNF in MDD may help repair neural damage in brain regions associated with brain disease, its repairing effects may be interfered with and hindered by underlying neuroinflammatory processes.

Altered gray matter volumes and plasma IL-6 level in major depressive disorder patients with suicidal ideation.

BACKGROUNDS: Suicidal ideation (SI) is one of the most serious consequences of major depressive disorder (MDD). Understanding the unique mechanism of MDD with SI (MDD + S) is crucial for treatment development. While abundant research has studied MDD, past studies have not reached a consensus on the mechanism of MDD + S. The study aimed to investigate the abnormalities of the gray matter volumes (GMVs) and plasma IL-6 level in MDD + S to further reveal the mechanism of MDD + S. METHODS: We tested the plasma IL-6 level using Luminex multifactor assays and collected the Structural Magnetic Resonance Imaging (SMRI) data from 34 healthy controls (HCs), 36 MDD patients without SI (MDD - S) and 34 MDD + S patients. We performed a partial correlation between the GMVs of the brain regions with significant differences and plasma IL-6 level with age, sex, medication, scores of HAMD-17 and HAMA as the covariates. RESULTS: Compared with HCs and MDD - S, MDD + S had significantly decreased GMVs in the left cerebellum Crus I/II and significantly increased plasma IL-6 level; compared with HCs, both the MDD + S and MDD - S had significantly decreased GMVs in right precentral and postcentral gyri. No significant correlation was found between the GMVs and the plasma IL-6 level in the MDD + S and MDD - S, respectively. While the GMVs of the right precentral and postcentral gyri negatively correlated with the level of IL-6 in the whole MDD (r = -0.28, P = 0.03). The GMVs of the left cerebellum Crus I/II (r = -0.47, P = 0.02), and the right precentral and postcentral gyri (r = -0.42, P = 0.04) negatively correlated with the level of IL-6 in HCs. CONCLUSION: The altered GMVs and the plasma IL-6 level may provide a scientific basis to understand the pathophysiological mechanisms of MDD + S.

Altered Levels of Plasma Inflammatory Cytokines and White Matter Integrity in Bipolar Disorder Patients With Suicide Attempts.

Objective: Bipolar disorder (BD) has a higher lifetime rate of suicide attempts (SA) than other psychiatric disorders. Furthermore, BD patients with SA (BD + S) are prone to a worse quality of life. However, the pathophysiology of BD + S is poorly understood. To further reveal the potential mechanisms of BD + S, abnormalities in peripheral plasma inflammatory cytokines and brain white matter (WM) in BD + S, as well as the correlation between them are investigated. Methods: We tested the levels of TNF-α, IL-1ß, and IL-6 in peripheral plasma and collected the diffusion tensor imaging (DTI) data from 14 BD + S, 24 BD patients without SA (BD-S), and 26 healthy controls (HCs). The three groups were matched by age and gender. The levels of TNF-α, IL-1ß, and IL-6 were detected by Luminex multifactor detection technology, and the fractional anisotropy (FA) values were employed to depict the alterations of WM. Partial correlation analyses were conducted to detect correlations between levels of TNF-α, IL-1ß, and IL-6 and changes of WM, and the relationships between severity of clinical symptoms, including scores of HAMD-17 and YMRS, and cytokine levels or FA values in all groups. Results: For plasma inflammatory cytokines, there was no significant difference in their levels except for IL-6 among the three groups. Post-hoc analyses revealed that increased IL-6 level was only detected in BD + S (p < 0.05, Bonferroni correction). For DTI, BD + S showed specifically decreased FA in the bilateral middle cerebellar peduncle and the left superior corona radiata compared to BD-S and HCs (p < 0.05, Bonferroni correction). Additionally, both BD + S and BD-S groups revealed decreased FA in the bilateral body and genu of corpus callosum (CC) compared to HCs (p < 0.05, Bonferroni correction). No significant correlation between plasma inflammatory cytokines and WM integrity was found. In the BD + S group, we found negative correlation between the scores of YMRS and FA values of the left middle cerebellar peduncle (r = -0.74, p = 0.035). Conclusion: The inflammation and impaired WM integrity may provide a scientific basis to understand the potential mechanisms of BD + S.

Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy.

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.

Prevalence of poor psychiatric status and sleep quality among frontline healthcare workers during and after the COVID-19 outbreak: a longitudinal study.

Poor psychiatric status and sleep quality were common among frontline healthcare workers (FHWs) during the outbreak of the 2019 novel coronavirus disease (COVID-19), but the change in these mental health outcomes overtime remained unknown. This study compared the psychiatric status and sleep quality of FHWs during and after the COVID-19 outbreak in China. FHWs who volunteered to work in Hubei province (the COVID-19 epicenter) were assessed at baseline during the COVID-19 outbreak and re-assessed when they returned to their place of origin (Liaoning province) after the COVID-19 outbreak. Participants' psychiatric status and sleep quality were measured with the Symptom CheckList-90 (SCL-90) and the Pittsburgh Sleep Quality Index (PSQI), respectively. A total of 494 FHWs was assessed at baseline and 462 at follow-up assessments. The prevalence of poor psychiatric status was 10.5% at baseline and increased to 14.9% at the follow-up assessment (P = 0.04). The corresponding figures of poor sleep quality at baseline and follow-up assessment were 16.4% and 27.9%, respectively (P < 0.001). Multiple logistic regression analysis found that severe fatigue (p = 0.003, OR = 1.266, 95% CI = 1.081-1.483), poor sleep quality (p < 0.001, OR = 1.283, 95% CI = 1.171-1.405), and history of pre-existing psychiatric disorders (p < 0.001, OR = 5.085, 95% CI = 2.144-12.06) were independently associated with higher odds of poor psychiatric status among the FHWs. Poor psychiatric status and sleep quality were common among FHWs during the COVID-19 outbreak, and the prevalence increased following their volunteer experiences. This suggests a critical need for longer-term psychological support for this subpopulation.