OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.
Animals ; Mice ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Cerebral Cortex ; Depression/physiopathology* ; Frontal Lobe/pathology*

OBJECTIVE: To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism. METHODS: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05). CONCLUSIONS YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
AMP-Activated Protein Kinases/metabolism* ; Adrenocorticotropic Hormone ; Animals ; Comorbidity ; Depression/drug therapy* ; Energy Metabolism ; Interleukin-6/metabolism* ; Myocardial Infarction/pathology* ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Tablets ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients. METHODS: A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls. RESULTS: Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (=-133.3 mg/L, 95%:-200.4--0.1, <0.01), subcortical infarction (=4.05, 95%:1.15-14.18, <0.05) and female (=2.54, 95%:1.04-6.23, <0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%:2.33-6.41, <0.01), PHQ-9 increased by 2.17 (95%:0.39--3.94, <0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%:-1.79--0.15, <0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (=4.27, 95%:1.40-13.10, <0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (=12.85, 95%:2.04-23.67, <0.05). CONCLUSIONS RLS is common in ischemic stroke patients and has adverse influences on patients.
Brain Ischemia ; complications ; pathology ; Depression ; complications ; Female ; Humans ; Male ; Polysomnography ; Restless Legs Syndrome ; complications ; pathology ; Stroke ; complications ; pathology

OBJECTIVE: The cognitive reserve theory explicates individual differences observed in the clinical manifestation of dementia despite similar brain pathology. Education, a popular proxy of the cognitive reserve, has been shown to have protective effects delaying the onset of clinical symptoms including memory. This study was conducted to test whether education can moderate the negative effect of depressive mood on memory performance in elderly women residing in the community. METHODS: 29 elderly “unschooled” female (less than 6 years of formal education) and 49 “schooled” female (6 or more years) people were compared with regard to association between depressive mood and verbal memory functioning, which were measured by the Geriatric Depression Scale and the Elderly Verbal Learning Test, respectively. RESULTS: The results showed that completing or receiving more than primary school education significantly reduced the negative association between depressive mood and memory performance. Participants who did not complete primary schooling showed a decline in memory test scores depending on the level of depressive mood; whereas participants who have completed or received more than primary education displayed relatively stable memory function despite varying level of depressive mood. CONCLUSION: Our findings imply that education in early life may have protective effects against memory impairment related to elderly depression.
Aged ; Brain ; Cognitive Aging ; Cognitive Reserve ; Dementia ; Depression ; Education ; Female ; Humans ; Individuality ; Memory ; Pathology ; Protective Factors ; Proxy ; Verbal Learning

PURPOSE: To analyze the psychosocial factors associated with central serous chorioretinopathy (CSC) according to its phases and subtypes and to correlate the factors with the extent of choroidal hyperpermeability. METHODS: Age- and sex-matched CSC patients and controls (n = 37 in each group) were enrolled, and their psychosocial factors were compared. CSC was divided into two phases (active and inactive), and active CSC was further divided into two subtypes (acute and chronic). The correlations between the size of the hyperpermeable choroidal lesion identified on indocyanine green angiography and psychosocial factors were examined. RESULTS: Active CSC patients experienced more stressful events (p = 0.030), were more depressive (p = 0.037), and felt less emotional (p = 0.014) and informational (p = 0.014) support than the matched controls, whereas inactive CSC patients were comparable to the matched controls in all psychosocial factors. Among the active CSC patients, acute patients were more depressive (p = 0.029), while chronic patients experienced more stressful events (p = 0.024) than their matched controls. The size of the hyperpermeable choroidal lesion was correlated with the severity of depression in acute patients. CONCLUSIONS: Association of CSC with psychosocial factors was dependent on the phase and subtype of CSC. Psychosocial factors were associated with CSC in the active phase, and severity of depression was correlated with the size of the choroidal pathology in acute active CSC. Further prospective studies to investigate if psychosocial factors can trigger CSC are warranted.
Angiography ; Anxiety ; Central Serous Chorioretinopathy* ; Choroid ; Depression ; Humans ; Indocyanine Green ; Life Change Events ; Pathology ; Prospective Studies ; Psychology* ; Stress, Psychological

To investigate the behavioral and biomolecular similarity between neuralgia and depression, a trigeminal neuralgia (TN) mouse model was established by constriction of the infraorbital nerve (CION) to mimic clinical trigeminal neuropathic pain. A mouse learned helplessness (LH) model was developed to investigate inescapable foot-shock-induced psychiatric disorders like depression in humans. Mass spectrometry was used to assess changes in the biomolecules and signaling pathways in the hippocampus from TN or LH mice. TN mice developed not only significant mechanical allodynia but also depressive-like behaviors (mainly behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis demonstrated common and distinctive protein changes in the hippocampus between groups. Many protein function families (such as cell-to-cell signaling and interaction, and cell assembly and organization,) and signaling pathways (e.g., the Huntington's disease pathway) were involved in chronic neuralgia and depression. Together, these results demonstrated that the LH and TN models both develop depressive-like behaviors, and revealed the involvement of many psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and LH.
Animals ; Avoidance Learning ; physiology ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; etiology ; pathology ; Disease Models, Animal ; Electroshock ; adverse effects ; Functional Laterality ; Helplessness, Learned ; Hindlimb Suspension ; psychology ; Hippocampus ; metabolism ; Male ; Mass Spectrometry ; Mice ; Mice, Inbred C57BL ; Orbit ; innervation ; Pain Measurement ; Proteomics ; methods ; Reaction Time ; physiology ; Signal Transduction ; physiology ; Trigeminal Neuralgia ; etiology ; pathology

The characteristic features of Alzheimer's disease (AD) are the appearance of extracellular amyloid-beta (Aβ) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aβ and NMDA receptors. Aβ-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.
Alzheimer Disease* ; Amygdala ; Amyloid ; Animals, Genetically Modified ; Atrophy ; Basal Ganglia ; Brain Stem ; Brain* ; Calcineurin ; Depression ; Hypothalamus ; Locus Coeruleus ; N-Methylaspartate* ; Neurofibrillary Tangles ; Neurons ; Neurotransmitter Agents ; Pathology* ; Phosphorylation ; Receptors, Glutamate ; Receptors, N-Methyl-D-Aspartate* ; Reticular Formation ; Risk Factors* ; Spine ; Substantia Nigra ; Synapses ; tau Proteins* ; Thalamus

Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.
Decidua ; Depression ; Epithelial Cells ; Epstein-Barr Virus Infections ; Female ; Gene Expression ; Herpesvirus 4, Human* ; Humans* ; Image Cytometry ; In Situ Hybridization ; Mass Screening ; Membranes ; Pathology ; Placenta* ; Pre-Eclampsia ; Pregnant Women ; RNA, Messenger ; Silver ; Stillbirth ; Virus Latency

BACKGROUNDElectroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients.

METHODSThis study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response.

RESULTSA total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response.

CONCLUSIONSThe FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.

Adult ; Brain ; pathology ; physiopathology ; Depression ; physiopathology ; therapy ; Depressive Disorder, Treatment-Resistant ; physiopathology ; therapy ; Electroconvulsive Therapy ; methods ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.
Adult ; Cadmium/blood ; Child Development/*physiology ; Cohort Studies ; Depression/epidemiology/*pathology ; Female ; Humans ; Infant ; Lead/blood ; Linear Models ; Male ; Malondialdehyde/blood ; Mothers/*psychology ; Prospective Studies ; *Stress, Psychological ; Surveys and Questionnaires