Gender differences in prevalence and associations between cognitive symptoms and suicidal ideation in patients with recurrent major depressive disorder: findings from the Chinese NSSD study.

BACKGROUND: This study aimed to explore gender differences in associations between cognitive symptoms and suicidal ideation (SI) among patients with recurrent major depressive disorder (MDD). METHODS: We recruited 1222 patients with recurrent MDD from the National Survey on Symptomatology of Depression (NSSD), a survey designed to investigate the symptoms experienced during current major depressive episodes in China. A four-point Likert questionnaire was used to assess the frequency of cognitive symptoms and SI in the past two weeks. RESULTS: Gender differences in clinical features and cognitive symptoms of participants with recurrent MDD were found. Specifically, male patients had a higher prevalence of memory loss, decreased verbal output, indecisiveness, and impaired interpersonal relationships, while female patients exhibited a higher prevalence of impaired social and occupational functioning (all P < 0.05). No significant difference in SI prevalence was found between male and female patients. The logistic regression analysis revealed that in male patients, SI was associated with indecisiveness and impaired interpersonal relationships. In female patients, reduced verbal output and impaired social and professional functions were also associated with SI in addition to the above-mentioned variables. CONCLUSION: The findings of gender differences in associations between cognitive symptoms and SI highlight the need to carefully assess gender-specific cognitive predictors of SI in patients with recurrent MDD. This has further implications for more targeted prevention and treatment strategies for SI based on gender.

HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation.

Group 2 innate lymphoid cells (ILC2s) are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13, which mediate the type 2 immune response. However, specific drug targets on lung ILC2s have rarely been reported. Previous studies have shown that type 2 cytokines, such as IL-5 and IL-13, are related to depression. Here, we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression. Interestingly, serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation. Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs. Furthermore, an HTR2A selective agonist (DOI) impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro. Mice with ILC2-specific depletion of HTR2A (Il5cre/+·Htr2aflox/flox mice) abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation. In conclusion, serotonin and DOI could restrict the type 2 lung immune response, indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ ILC2s.

Employing biochemical biomarkers for building decision tree models to predict bipolar disorder from major depressive disorder.

BACKGROUND: Conventional biochemical parameters may have predictive values for use in clinical identification between bipolar disorder (BD) and major depressive disorder (MDD). METHODS: This study enrolled 2470 hospitalized patients with BD (n = 1333) or MDD (n = 1137) at reproductive age from 2009 to 2018 in China. We extracted 8 parameters, uric acid (UA), direct bilirubin (DBIL), indirect bilirubin (IDBIL), lactic dehydrogenase (LDH), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), high-density lipoprotein (HDL) and prealbumin of male, patients and 12 parameters, UA, DBIL, IBIL, LDH, FT3, TSH, glutamic-pyruvic transaminase (GPT), white blood cell (WBC), alkaline phosphatase (ALP), fasting blood glucose (FBG), triglyceride and low-density lipoprotein (LDL) of female patients. Backward stepwise multivariate regression analysis and the Chi-Square Automatic Interaction Detection (CHAID) segmentation analysis via SPSS Decision Tree were implemented to define the discrimination of BD and MDD. RESULTS: DBIL was extracted as the first splitting variable, with LDH and IBIL as the second, TSH and prealbumin as the third in the model of male patients (p-value < .05). For the model of female patients, DBIL was also extracted as the first splitting variable, with UA, LDH, and IBIL as the second, triglyceride and FT3 as the third (p-value < .05). The predictive accuracies of the Decision Tree and multiple logistic regression models were similar (74.9% vs 76.9% in males; 74.4% vs 79.5% in females). CONCLUSIONS: This study suggests the value of the Decision Tree models, which employ biochemical parameters as diagnostic predictors for BD and MDD. The CHAID Decision Tree identified that patients with concomitantly increased LDH, IBIL, and decreased DBIL could be in the group that showed the highest risk of being diagnosed as BD.

Comorbidity and Treatment in Older Psychiatric In-patients-A Retrospective Study in a Chinese Psychiatric Hospital.

Background: Comorbid somatic diseases increase the death risk and affect the condition, treatment, and prognosis of older psychiatric patients. We investigated the comorbidity and drug treatment in older patients with psychosis. Methods: This retrospective study used data from 3,115 older psychiatric in-patients hospitalized at the Shanghai Mental Health Center Affiliated to Shanghai Jiaotong University School of Medicine, China discharged from 2005 to 2015. Descriptive analyses of patients' age, sex, treatment drugs, diagnoses (based on ICD-10), and time trend were performed. Results: Patients' median age was 56 (range, 50-98) years; 1,824 (58.6%) were female. The top five first-level diagnoses were schizophrenia (F20) (n = 1,818, 58.3%), depressive episode (F32) (n = 457, 14.6%), bipolar affective disorder (F31) (n = 151, 4.8%), manic episode (F30), (n = 143, 4.6%), and vascular dementia (F01) (n = 136, 4.4%). Mental (99.9%), central nervous system (85.2%), digestive system (83.5%), cardiovascular system (72.5%), and anti-infective (59.6%) drugs had the highest prescription rates. The combined use of antidepressants, anti-anxiety, anti-arrhythmic, hormones and endocrine system drugs were significantly higher in female than in male patients, while mood stabilizers and genitourinary system drugs significantly more frequent in men. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased, with the corresponding changes to prescription in those patients. In comparison to that in 2005-2010, the combined prescriptions for genitourinary and cardiovascular drugs increased between 2011 and 2015, and F00-F09 and F40-F48 older patients doubled, accordingly anti-Alzheimer's disease drugs and antidepressants more than doubled. F30-F39 patients increased by 49.1%, and anti-anxiety drugs, mood stabilizers, etc. increased by ≥50%; F20-F29 older patients decreased by 26.7%, while antipsychotics only increased by 4.4%. Conclusions: This study found the combined drug treatment of somatic diseases, particularly for central nervous, digestive, cardiovascular, respiratory and genitourinary drugs were extremely common among older psychiatric in-patients in China. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased; the antipsychotics prescriptions decreased, and almost all comorbidity drugs increased. Compared with that in 2005-2010, the older patients with all diagnosis except F20-F29 increased in 2011-2015, and the prescriptions for psychotropic, genitourinary, and cardiovascular drugs increased.

PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol.

BACKGROUND: Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome. METHODS AND ANALYSIS: This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to 'escitalopram+golimumab (TNF-α inhibitor)', 'escitalopram+calcium tablet+vitamin D (PKC activator)' or 'escitalopram+placebo' groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life. DISCUSSION: This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression. TRIAL REGISTRATION NUMBER: The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.

Neural biomarker of functional disability in major depressive disorder: A structural neuroimaging study.

BACKGROUND: Most patients with the major depressive disorder (MDD) have varying degrees of impaired social functioning, and functional improvement often lags behind symptomatic improvement. However, it is still unclear if certain neurobiological factors underlie the deficits of social function in MDD. The aim of this study was to investigate the biomarkers of social function in MDD using structural magnetic resonance imaging (MRI). METHODS: 3T anatomical MRI was obtained from 272 subjects including 46 high-functioning (high-SF, Sheehan Disability Scale (SDS) rating < 18) and 63 low-functioning (low-SF, SDS score ≥ 18) patients with MDD and 163 healthy controls (HC). Voxel-based morphometry (VBM) was employed to locate brain regions with grey matter (GM) volume differences in relation to social function in MDD. Regions showing GM differences in relation to social function at baseline were followed up longitudinally in a subset of 38 patients scanned after 12-week treatment. RESULTS: Volume of right parahippocampal gyrus (rPHG) was significantly reduced in low-SF patients with MDD when compared to high-SF ones (FDR-corrected p < 0.05). Over 12 weeks of follow-up, though SF improved overall, the high and low-SF subgroups continued to differ in their SF, but had no progressive changes in PHG volume. LIMITATIONS: Limited functional assessment, high drop-out rate and median-based grouping method. CONCLUSIONS: Greater GM volume (GMV) of the rPHG may mark better social function in patients with MDD.

Exploring the Effects of Temperament on Gray Matter Volume of Frontal Cortex in Patients with Mood Disorders.

BACKGROUND: Patients with bipolar disorder (BD) and patients with major depressive disorder (MDD) have relatively specific temperament and structural abnormalities of brain regions related to emotion and cognition. However, the effects of temperament factors on the structure of frontal and temporal cortex is still unclear. The aims of this study were to explore the differences and relationships between temperament characteristics and the gray matter volume of frontal and temporal cortex in patients with BD or MDD. METHODS: T1-weighted magnetic resonance imaging (MRI) data, demographic and clinical information were obtained from 279 depressed patients (90 patients with BD, 189 patients with MDD) and 162 healthy controls (HC). Temperament was assessed with the Chinese short version of Temperament Evaluation of Memphis, Pisa and San Diego - Auto questionnaire (TEMPS-A). The Desikan-Killiany atlas was used for yielding gray matter volume by FreeSurfer 6.0 software suite. A total of 22 frontal and temporal regions were chosen as regions of interest (ROIs). RESULTS: Compared with patients with MDD, patients with BD had higher TEMPS-A total scores and scores on cyclothymic, irritable and hyperthymic subscales. The gray matter volume in bilateral rostral middle frontal gyrus (RMFG), left temporal pole and right superior frontal gyrus were reduced in patients with BD. Patients with MDD only had lower gray matter volume in bilateral temporal pole. In the pooled patients, there were negative associations between hyperthymia and gray matter volume in right RMFG. CONCLUSION: Patients with BD and MDD had different temperament characteristics. The prominent temperament subscales in patients with BD were cyclothymia, irritable and hyperthymia. Patients with greater hyperthymia had lower gray matter volume in right frontal gyrus. Temperament may reflect an endophenotype in patients with mood disorders, especially in BD.

Probing the clinical and brain structural boundaries of bipolar and major depressive disorder.

Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroanatomical features. Brain structural data were obtained at 3 T from a sample of 90 patients with BD, 189 patients with MDD, and 162 healthy individuals. We applied sparse partial least squares discriminant analysis (s-PLS-DA) to identify clinical and brain structural features that may discriminate between the two clinical groups, and heterogeneity through discriminative analysis (HYDRA) to detect patient subgroups with reference to healthy individuals. Two clinical dimensions differentiated BD from MDD (area under the curve: 0.76, P < 0.001); one dimension emphasized disease severity as well as irritability, agitation, anxiety and flight of ideas and the other emphasized mostly elevated mood. Brain structural features could not distinguish between the two disorders. HYDRA classified patients in two clusters that differed in global and regional cortical thickness, the distribution proportion of BD and MDD and positive family history of psychiatric disorders. Clinical features remain the most reliable discriminant attributed of BD and MDD depression. The brain structural findings suggests that biological partitions of patients with mood disorders are likely to lead to the identification of subgroups, that transcend current diagnostic divisions into BD and MDD and are more likely to be aligned with underlying genetic variation. These results set the foundation for future studies to enhance our understanding of brain-behavior relationships in mood disorders.

Common cellular and molecular mechanisms and interactions between microglial activation and aberrant neuroplasticity in depression.

It has been suggested that inflammation is involved in the pathophysiology of depression. As tissue-specific macrophages in the central nervous system (CNS), microglia play an important role in neuroinflammation. Resident microglia become activated towards the pro-inflammatory (M1) phenotype or the anti-inflammatory (M2) phenotype during neuroinflammation. In the CNS, neurons report to microglia regarding their statuses and can regulate microglial activation, while microglia also modulate neuronal activities, including neuroplasticity. The molecular mechanisms underlying the communication between microglia and neurons, which include intracellular and extracellular signalling pathways, might be complex and of great importance for new research on the pathogenesis of depression. The present review aims to discuss the common cellular and molecular mechanisms for microglial activation and aberrant neuroplasticity in depression and the role of these processes in the pathogenesis of depression.

Lack of Association Between PLA2G6 Genetic Variation and Parkinson's Disease: A Systematic Review.

BACKGROUND: The phospholipase A2 Group 6 (PLA2G6, also known as PLA2, PARK14, and iPLA2) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of PLA2G6 has been indicated to be involved in conferring susceptibility for Parkinson's disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if PLA2G6 genetic variation confers a greater susceptibility to PD. METHODS: All case-control studies that investigated the association of the PLA2G6 polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association. RESULTS: A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between PLA2G6 genetic variation and PD susceptibility. CONCLUSION: The present study assessed the association of PLA2G6 genetic polymorphism with the risk PD, and the result strongly demonstrates that PLA2G6 polymorphism is not associated with PD susceptibility.

Altered resting-state fMRI signals and network topological properties of bipolar depression patients with anxiety symptoms.

BACKGROUND: This study aims to explore the changes in functional neuroimaging in bipolar depression patients with anxiety symptoms (BDP-A). METHODS: Forty-five BDP-A patients, 22 bipolar depression patients without anxiety symptoms (BDP-NA), and 48 healthy controls (HC) were finally involved. The low-frequency oscillation characteristics, functional connectivity (FC), and network properties among the three groups of participants were analyzed. RESULTS: Compared with the BDP-NA group, BDP-A patients exhibited significantly decreased amplitude of low-frequency fluctuation (ALFF) in the left middle frontal gyrus (MFG), superior occipital gyrus, and inferior parietal, but supramarginal and angular gyri (IPL). Enhanced FC from left IPL to middle temporal gyrus, from left precentral gyrus (PreCG) to bilateral angular gyri, medial superior frontal gyrus, and left superior frontal gyrus (SFG)/MFG were also revealed. Compared with HC, the BDP-A group showed remarkably increased ALFF in the left MFG/PreCG, right superior parietal gyrus, while decreased ALFF in the left inferior frontal gyrus, opercular part, and SFG. In addition, higher regional homogeneity in the left MFG/PreCG was found. LIMITATIONS: The limitations are as follows: (1) relatively small sample size; (2) not all the patients were drug-naive; (3) lack of pure anxiety disorder patients as a controlled group; (4) mental health conditions of HC were not systemic evaluated. CONCLUSIONS: BDP-A patients showed significant differences in resting-state fMRI properties when compared with BDP-NA or HC group. These results may infer the dysfunction of the dorsal attention network, the default network, and the fronto-limbic system as well as disrupted brain network efficiency in BDP-A patients.

Variants in the Upstream Region of the Insulin Receptor Substrate-1 Gene Is Associated with Major Depressive Disorder in the Han Chinese Population.

INTRODUCTION: Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders, although its underlying genetic mechanism remains unknown. Insulin receptor substrate-1 (IRS-1) is one of the critical downstream molecules in the insulin resistance signaling pathway, linking depression and diabetes. Therefore, we hypothesized that IRS-1 would be a susceptible gene for MDD, and we aimed to examine the genetic association between IRS-1 and MDD. METHODS: This case-control study included 583 patients with MDD and 564 controls, and the genotypic and allelic distributions of the IRS-1 gene's four single nucleotide polymorphisms (SNPs) were detected by TaqMan SNP genotyping technology. Of the 583 patients, 191 underwent a further detailed interview about symptom severity and family history of mental illness. The chi-square or t test was used to analyze the data, and analyses were performed using SPSS19.0 software. RESULTS: A haplotype in the 5'-upstream region of IRS-1 consisting of rs13411764 and rs3820926 was a risk factor of MDD. Patients with a family history of mental illness were more likely to have a GG genotype in rs13411764 and a G-T haplotype containing rs13411714-rs3820926. DISCUSSION: The findings imply that the haplotype consisting of rs13411764 and rs3820926 in the upstream of IRS-1 is a risk factor for MDD. This haplotype could affect IRS-1 expression levels, and it is mostly inherited from parents. Thus, the presence of variants in the upstream region of IRS-1 is a risk factor of MDD, and this study could serve as a convincing reference for further studies.

Introduction.

Depressive disorder is one of the most widespread forms of mental disorders which lead to a significant public health concern, such as disability, suicide, and so on. Its etiology remains vague but it is believed that depressive disorder is a multifactorial disease which is induced by the interaction of social, psychological, and biological factors. Thus, there is no clear and definite pathological theory could illustrate its mechanism independently until now, involving genetics, neuroimaging, neuroinflammation, neuroendocrine, and others. Comprehensive assessment to patients with depression is the starting point for a right diagnosis. History-taking of physical condition is as important as psychiatric interview and rational usage of scales would be beneficial for screening. There are many kinds of therapeutic measures for depressive patients nowadays, including general intervention, pharmacotherapy, psychotherapy, and physical therapy. For now, anti-depressants used in clinical practice is almost monoamine-based drugs while much more progress have been made in developing new antidepressant medications, like prototypical N-methyl-D-aspartate (NMDA) receptor antagonists, opioid agonists, gamma-aminobutyric acid (GABAA) receptors, and psychedelics. Once these novel drugs are proved to be practicable, it will create a historical evolution in the field of psychiatry. In addition, we advocate that measurement-based care (MBC) should run through the whole duration of treatment and goals of MBC in every stage are different. As brain projects in many countries are conducting in inspiring ways, we believe that our understanding about depressive disorder, of course, and other neuropsychiatric disorders will be better in the future.

Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products.

Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.

Effects of tumor necrosis factor-α polymorphism on the brain structural changes of the patients with major depressive disorder.

Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center. Voxel-based morphometry (VBM) followed by graph theory based structural covariance analysis was applied to locate diagnosis x genotype interactions. Irrespective of diagnosis, individuals with the high-risk genotype (T-carriers) had reduced volume in left angular gyrus (main effect of genotype). Diagnosis x genotype interaction was exclusively localized to the visual cortex (right superior occipital gyrus). The same region also showed reduced volume in patients with MDD than HC (main effect of diagnosis), with this effect being most pronounced in patients carrying the high-risk genotype. However, neither global nor regional network of structural covariance was found to have group difference. In conclusion, a genetic variation which can increase TNF-α expression selectively affects the anatomy of the visual cortex among the depressed subjects, with no effect on the topographical organization of multiple cortical regions. This supports the notion that anatomical changes in depression are in part influenced by the genetic determinants of inflammatory activity.

Abnormal white matter integrity in Chinese young adults with first-episode medication-free anxious depression: a possible neurological biomarker of subtype major depressive disorder.

BACKGROUND: Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method. SUBJECTS AND METHODS: DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed. RESULTS: When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group. CONCLUSION: The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD.

The association of duration and severity of disease with executive function: Differences between drug-naïve patients with bipolar and unipolar depression.

BACKGROUND: The aims of this study were to investigate the differences in executive function and the relationship with clinical factors between drug-naïve patients with bipolar depression (BDD) and unipolar depression (UPD). METHODS: Drug-naïve patients with BDD, UPD and healthy controls (HC) were recruited (30 cases in each group). All patients were assessed with Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression-17 (HAM-D), and Young Mania Rating Scale (YMRS). Executive function was evaluated by Stroop color-word test (CWT) and Wisconsin Card Sorting Test (WCST). RESULTS: In the BDD group, only the CWT number of missing was higher than HCs (P = 0.047). In the UDP group, CWT number of correct was lower, CWT number of missing was higher, and the WCST indices were worse than the HC group (P < 0.05). The WCST percentage of errors (PE) and percentage of conceptual level responses (PCLR) in the UPD group were worse than the BDD group (P < 0.05). In the BDD group, no correlations between CWT and WCST indices and clinical features were detected after correcting for multiple comparisons (P > 0.05). In the UDP group, the WCST PE, PCLR, number of categories completed (CC), and the percentage of perseverative responses (PPR) were correlated to the number of mood episodes (P < 0.01). LIMITATION: This was a small-sample cross-sectional study. The possibility of UPD transforming to bipolar disorder (BD) in future could not be ruled out. CONCLUSION: Our results suggested only small differences in executive function between drug-naïve patients with BDD and UPD, but in this sample only the UPD group showed differences with HCs. The executive function of drug-naïve BDD patients may be associated with duration of current depressive episode, while for UDP patients executive function indices were significantly correlated with number of mood episodes.

Different levels of pro- and anti-inflammatory cytokines in patients with unipolar and bipolar depression.

BACKGROUND: Immune system dysregulation is critical in the physiopathology of major depressive disorder (MDD) and bipolar disorder (BD). However, it is unclear whether both diseases present the same inflammatory patterns during depressive episodes. We explored the differences in pro- and anti-inflammatory cytokines between unipolar and bipolar depression (BDD) and the trajectory of these cytokines after acute-phase treatment. METHODS: Sixty-four MDD patients, 61 BDD patients, and 62 healthy controls (HCs) were enrolled. We assessed the clinical features and cytokines plasma levels at baseline and week 12. The pro-inflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokines (IL-4, IL-13) of all subjects were assessed by multiplexed sandwich ELISA-based quantitative arrays. RESULTS: Before acute-phase treatment, the initial levels of TNF-α and IL-13 were significantly lower in the BDD patients than in the MDD patients. The results demonstrated that there was no relationship between each cytokine level and clinical features of unipolar and bipolar depressions. After 12 weeks, TNF-α, IL-4, and IL-13 levels became lower in MDD patients than in the other two groups regardless of the patients' response to treatment while the levels of TNF-α and IL-4 increased only in the BDD responders. LIMITATIONS: The effects of different drugs on inflammatory cytokines in MDD or BDD could not be explored further due to the relatively small sample size. CONCLUSION: Even within the same depressive states, MDD and BDD patients present different inflammatory features, particularly in regard to pro-inflammatory TNF-α and anti-inflammatory IL-13. In addition, the fluctuations of cytokines induced by medication may provide a hint regarding the prediction of treatment response.

An insertion/self-fusion mechanism for cell membrane immobilization on porous silica beads to fabricate biomimic carriers.

Immobilization of membrane proteins on solid supports with high stability, favorable reusability and prevention of contamination is of great interest in nanobiology and medicine. Cell membrane coating technology enables the membrane proteins associated with their surrounding membranes to co-immobilize onto the solid matrix, largely enhancing the loading efficiency and conserving the bioactivity of the membrane proteins. Herein, we systematically illustrate the mechanism of cell membrane immobilization on porous silica beads, facilitating the fabricated biomimic carriers applied for chromatography. Rabbit red blood cell membranes were obtained via a low permeability swelling method. Batch immobilization studies were carried out to investigate the effects of the pore size of porous silica beads and incubation time on cell membrane immobilization. The absorption behavior of cell membranes could be well described by a pseudo-second-order kinetic model and the Freundlich model (a multilayer adsorption process) at 298 K, demonstrating an insertion/self-fusion mechanism involved in cell membrane coating onto the surface of porous silica beads. The insertion/self-fusion mechanism was further confirmed by confocal imaging and transmission electron microscopy.