Objective To explore the changes in serum lactate dehydrogenase （LDH）， monocyte chemoattractant protein-1 （MCP-1）， and transcription factor 4 （TCF4） levels in patients with cerebral small vessel disease complicated by depression and their clinical significance. Methods According to the inclusion and exclusion criteria， 90 patients admitted to the Kailuan General Hospital between January 2022 and August 2024 were selected as the study subjects， including 27 patients diagnosed with cerebral small vessel disease complicated by depression and 63 patients with cerebral small vessel disease uncomplicated by depression. An additional 45 healthy individuals with normal head MRI findings and no mental disorders during the same period at the hospital were selected as the control group. General information was collected from the three groups， including age， body mass index， systolic blood pressure， and diastolic blood pressure.The general information and the levels of serum LDH，MCP-1，and TCF4 in the three groups were compared. The correlations of serum LDH，MCP-1，and TCF4 levels with HAMD score in patients with cerebral small vessel disease and depression were analyzed. Logistic regression was applied to analyze possible factors leading to depression in patients with cerebral small vessel disease.The receiver operating characteristic curve was applied to analyze the efficacy of serum LDH， MCP-1， and TCF4 levels in diagnosing depression in patients with cerebral small vessel disease. Results The levels of serum LDH， MCP-1，and TCF4 were significantly higher in the cerebral small vessel disease complicated by depression group than in cerebral small vessel disease uncomplicated with depression group and the control group （P<0.05）， and these levels were significantly higher in the cerebral small vessel disease uncomplicated with depression group than in the control group （P<0.05）.The serum LDH，MCP-1 and TCF4 were positively correlated with HAMD score in patients with cerebral small vessel disease complicated with depression（r=0.606，0.798，0.672，all P<0.001）.Serum LDH， MCP-1， and TCF4 were influencing factors for depression in cerebral small vessel disease（P<0.05）.The area under the receiver operating characteristic curve of LDH， MCP-1，and TCF4 in combination in the diagnosis of depression in cerebral small vessel disease was 0.917， which was superior to serum LDH， MCP-1， and TCF4 alone （ZLDH-combination=2.457，P=0.014；ZMCP-1-combination=2.384， P=0.017； ZTCF4-combination=2.317， P=0.021）. Conclusion Serum LDH， MCP-1， and TCF4 levels increased in patients with cerebral small vessel disease complicated with depression. Their combination is valuable in the diagnosis of cerebral small vessel disease complicated with depression.
Depression

Objective To investigate the changing trend of sleep disturbance in patients with hepatolenticular degeneration and the bidirectional relationship between sleep disturbance and depression through a cross-lagged regression analysis. Methods A total of 80 patients who met the diagnostic criteria for WD from January to June 2024 were enrolled in this longitudinal study and were followed up for 3 months.Pittsburgh Sleep Quality Index （PSQI） was used to assess sleep quality， and Beck Depression Inventory （BDI） was used to assess the severity of depression， at the time of enrollment （T0）， at 1 month after enrollment （T1），and at 2 months after enrollment （T3）. An unconditional growth model was used to analyze the trajectory of sleep disturbance， and a cross-lagged regression model was used to investigate the temporal relationship between sleep disturbance and depression. Results From T0 to T2， there were significant increases in PSQI and BDI scores in all WD patients（P<0.05）. The variance of the intercept factor （the initial status of sleep disturbance） was estimated at 10.83（P<0.01），and the variance of the slope factor （the rate of change in sleep disturbance） was 1.20 （P<0.01），with a significant negative correlation between the intercept and the slope （r=-0.25，P<0.01）. The correlation analysis of PSQI and BDI scores across the three time points revealed a positive correlation between PSQI and BDI scores （r∈[0.19，0.96]，P<0.01）.The cross-lagged model analysis showed that sleep disturbance significantly predicted subsequent depression （P<0.01），with standardized regression coefficients （β） of 0.392 and 0.347， respectively； meanwhile， depression also significantly predicted subsequent sleep disturbance （P<0.01）， with β of 0.273 and 0.372， respectively. These findings suggested a bidirectional predictive relationship between sleep disturbance and depression in WD patients over time. Conclusion There is a bidirectional relationship between sleep disturbance and depression in patients with WD， and depression has a more pronounced influence on sleep disturbance. Therefore， clinical interventions should focus on both sleep and psychological state， and combined management should be performed to improve the effect of disease control.
Depression

Objective Observational studies have shown an association between Parkinson disease （PD） and mental illness， but further studies are needed to explore the causal relationship between them. This study aims to investigate such causal relationship using the method of two-sample Mendelian randomization （MR）. Methods Related data were extracted from GWAS， and summary statistics associated with PD， depression， sleep disorders， and anxiety phenotype-variants were obtained. Single nucleotide polymorphisms （SNPs） for PD were selected as instrumental variables， and MR-PRESSO was used to exclude outliers. Inverse variance weighting was used as the main method to assess causal effect estimates， and MR Egger， weighted median， simple mode， and weighted mode were used to verify the robustness of the findings. A sensitivity analysis was used to validate the reliability of the results， including the Cochran Q test， the MR-Egger intercept test， funnel plots， and the leave-one-out method. Results A total of 21 SNPs associated with PD were identified. The MR analysis showed that PD had a causal relationship with depression （OR=0.974，95%CI 0.934‒1.015， P=0.210）， sleep disorders （OR=1.056， 95%CI 0.970-1.149， P=0.211）， and anxiety （OR=0.998， 95%CI 0.996‒1.001， P=0.118）， with no statistical significance. Different MR analyses and sensitivity analyses showed that PD did not directly contribute to the development of mental illness. Conclusion There is no direct causal relationship between PD and depression/sleep disorders/anxiety. In clinical practice， healthcare professionals should pay attention to the mental health of patients with PD. Randomized controlled studies should be conducted in the future to further validate the results of this study.
Depression ; Anxiety

Depression is a mental health condition that affects more than 3.3 million Filipinos. Screening of adults and elderly patients is recommended with the use of validated tools like the Patient Health Questionnaire (PHQ-2 or PHQ-9) or the Geriatric Depression Scale-15 (GDS-15). The two-step approach can be followed for adults by using the PHQ-2 first, followed by the PHQ-9 if the PHQ-2 tests positive. Geriatric patients may be screened using the GDS-15 tool or PHQ-9. Diagnostic work-up should be done to rule out metabolic or organic conditions that can mimic or cause depression. Diagnosis of depression should be confirmed using the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Referral to a specialist should be done in cases of severe depression, psychosis, high suicide risk, severe malnutrition, pregnant adults, or non-response to initial treatment.

OBJECTIVES: To explore the values of materialism in medical postgraduates and its relationship with depression. METHODS: We conducted a survey among 592 postgraduates in clinical medicine using Materialism Tendency Scale (MTS) and Patient Health Questionnaire-9 (PHQ-9). Descriptive analysis, mean comparison, and correlation analysis were used for data analysis. RESULTS: The postgraduates had a mean total score of materialism of 56.36±10.44, and 11.8%, 54.1%, and 34.1% of them reported high, medium, and low levels of materialism, respectively. No significant differences were found in the total score of materialism among the postgraduates of different genders or with different family economic levels, but the postgraduates from urban families had a significantly higher level of materialism than those from rural families (P<0.001). 18.4% of the postgraduates screened positive for moderate to severe depressive symptoms. The total score of MTS was positively correlated with depression (r=0.289, P<0.001). The dimension scores of MTS for materialism obsessions, material vanity, material interest, and material pursuit were all positively correlated with depression (r=0.183-0.289, P<0.001). The depressive symptoms and their overall levels differed significantly among individuals with different levels of materialism, and higher levels of materialism were associated with severer depressive symptoms (F=18.792, P<0.001) and a higher positive rate of depression (χ²=27.528, P<0.001). CONCLUSIONS Materialistic values may increase the risk of depression among medical postgraduates.
Humans ; Depression/epidemiology* ; Surveys and Questionnaires ; Female ; Adult ; Male ; Middle Aged ; Risk Factors

OBJECTIVES: To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. METHODS: Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. RESULTS: The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. CONCLUSIONS C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.
Animals ; Female ; Depression, Postpartum ; Complement C1q/metabolism* ; Antibodies, Neutralizing/pharmacology* ; Mice, Inbred C57BL ; Mice ; Hippocampus/metabolism* ; Pregnancy ; Disease Models, Animal

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features. Using single-nucleus RNA sequencing, we identified cell-specific transcriptomic changes in the nucleus accumbens (NAc), particularly in astrocytes, of adolescent macaques exhibiting depressive-like behaviors. The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques, while FKBP5 levels increased in glial cells. Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons (MSNs) and subtypes of astrocytes. Communication pathways between astrocytes and D1/D2-MSNs were also disrupted, involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4. Bulk transcriptomic and proteomic analyses corroborated these findings, and FKBP5 upregulation was confirmed by qRT-PCR, western blotting, and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress. Our results highlight the specific roles of different cell types in adolescent depression in the NAc, offering potential targets for new antidepressant therapies.
Animals ; Nucleus Accumbens/metabolism* ; Male ; Transcriptome ; Depression/genetics* ; Astrocytes/metabolism* ; Neurons/metabolism* ; Rats