Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression

BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of suicide.In studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is sparse.Some researchers even mistakenly regard the signals generated by the WM as noise points.In fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations.The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.AIM To explore potential abnormalities in WM functional signals in adolescents with MDD.METHODS This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide inventory.In addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image data.The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC groups.Independent component analysis(ICA)was also used to evaluate the WM functional signal.Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.RESULTS Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel correction).The ICA results of WM overlapped with those of regional homogeneity.The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale(P=0.026,r=-0.32),and the right posterior corona radiata was also negatively correlated with the MINI suicide scale(P=0.047,r=-0.288).CONCLUSION Adolescents with MDD involves changes in WM functional signals,and these differences in brain regions may increase the risk of suicide.

Attribution retraining group therapy for outpatients with major depression disorder,generalized anxiety disorder,and obsessive-compulsive disorder:a pilot study

The aim of this present study is to examine the efficacy of attribution retraining group therapy （ARGT） and to compare the responses of outpatients with major depression disorder （MDD）, generalized anxiety disorder （GAD） and obsessive-compulsive disorder （OCD）. We carried out a prospective uncontrolled intervention study with a 8-weeks of ARGT on sixty three outpatients with MDD, GAD or OCD. Hamilton rating scale for depression, Hamilton rating scale for anxiety, Yale-Brown obsessive-compulsive scale, attribution style questionnaire, self-esteem scale, index of well-being, and social disability screening schedule were administered before and after treatment. Significant improvement in symptoms and psychological and social functions from pre- to posttreatment occurred for all participants. The changes favored MDD patients. Our study suggested that ARGT may improve the symptoms and psychological-social functions of MDD, GAD, and OCD patients. MDD patients showed the best response.

Serum levels of chemokines in adolescents with major depression treated with fluoxetine

BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.

Current progress in neuroimaging research for the treatment of major depression with electroconvulsive therapy

Electroconvulsive therapy(ECT)uses a certain amount of electric current to pass through the head of the patient,causing convulsions throughout the body,to relieve the symptoms of the disease and achieve the purpose of treatment.ECT can effectively improve the clinical symptoms of patients with major depression,but its therapeutic mechanism is still unclear.With the rapid development of neuroimaging technology,it is necessary to explore the neurobiological mechanism of major depression from the aspects of brain structure,brain function and brain metabolism,and to find that ECT can improve the brain function,metabolism and even brain structure of patients to a certain extent.Currently,an increasing number of neuroimaging studies adopt various neuroimaging techniques including functional magnetic resonance imaging(MRI),positron emission tomography,magnetic resonance spectroscopy,structural MRI,and diffusion tensor imaging to reveal the neural effects of ECT.This article reviews the recent progress in neuroimaging research on ECT for major depression.The results suggest that the neurobiological mechanism of ECT may be to modulate the functional activity and connectivity or neural structural plasticity in specific brain regions to the normal level,to achieve the therapeutic effect.

Switch from previous major depression comorbid with CLIPPERS to mania-like episode following glucocorticosteroid therapy:a case report

Bipolar disorder is associated with high rates of general medical conditions, but few cases of overlap between bipolar disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids(CLIPPERS) have been reported in the current literature. The following is a case of a 29-year-old patient with a previous major depressive episode comorbid with CLIPPERS. Following glucocorticosteroid therapy, the patient switched to mania-like presentation and was diagnosed with bipolar disorder due to another medical condition. So it is strongly suggested that high-dose corticosteroid pulse therapy could easily induce psychiatric disturbances for patients with previous psychiatric symptoms, and there may be potential links between bipolar disorder and CLIPPERS in the area of inflammation.

Self-Frustration of Expectations in Major Depressive Disorder: The Syncytiopathy Hypothesis of Depression Revisited

This paper is a further elaboration of my model of the pathophysiology of major depressive disorder focusing on imbalances of glial-neuronal interactions in tripartite synapses and the glial network (syncytium). Basically, it is proposed that the connexin proteins building gap junctions in the glial syncytium are underexpressed or dysfunctional in major depression, called syncytiopathy. As a compensatory effect the astrocytic receptors in tripartite synapses are overexpressed. This leads to protracted synaptic information processing because of a relative lack of neurotransmitter substances for the occupancy of astrocytic receptors. Based on a new biophysical formal description of astrocytic receptors as expectation variables it can be shown that the protracted processing of sensory information frustrate the full comprehension of the expected event, since it cannot be grasped in time. Moreover, expectation frustration may stress the glial syncytium aggravating memory impairment. This cyclic process of dysbalanced synaptic information processing is characterized as self-frustration of expectations explanatory for the main cognitive dysfunctions in major depression as slowing down processing speed, deficits in attention and working memory. The main result of the study is that patients with major depression cannot fully acknowledge the existence of an intended event.

Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life： Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012

Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns ofantipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life （QOL）. Methods： A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients＇ socio-demographic and clinical characteristics including psychopathology, medication side effects. satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. Results： The frequency ofantipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively （χ^2 = 90.3, df= 2, P 〈 0.001 ）. Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals （i.e., Level-Ⅲ hospital）. Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. Conclusions： Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients＇ and relatives＇ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

Microstructural brain abnormalities,affective temperaments,and suicidal behavior in patients with major depression

According to magnetic resonance imaging(MRI)studies,brain white matter(WM)abnormalities have been suggested to play a critical role in the pathogenesis of major depressive disorder(MDD)and related suicidal behavior.However,MRI findings may be limited by low spatial resolution;therefore,an important contribution to the understanding of the role and significance of WM alterations derived by the development of the most recent magnetic resonance techniques,such as diffusion tensor imaging(DTI).Several DTI studies reported an association between altered WM integrity and MDD/suicidal behavior.Microstructural WM abnormalities may be located in neural circuits critically implicated in emotional processes and mood regulation resulting in enhanced vulnerability to psychiatric morbidity.WM abnormalities detected using DTI may contribute to functional deficits and help to clarify the pathophysiological mechanisms underlying MDD as well as suicidal behavior.By a clinical point of view,research also suggested that affective temperaments may play a relevant role in the psychopathological characteristics of mood disorders,clinical trajectory of episodes and polarity,long‑term outcome and suicidality.Unfortunately,only few studies investigated the association between affective temperaments and WM abnormalities and discussed their possible implications in patients with MDD and suicidal behavior.Using a comprehensive search of Medline database,the aim of the present study was to critically review the current literature on the association between WM alterations as assessed by MRI and DTI techniques,affective temperaments,MDD and suicidal behavior.

3DMKDR:3D Multiscale Kernels CNN Model for Depression Recognition Based on EEG

Depression has become a major health threat around the world,especially for older people,so the effective detection method for depression is a great public health challenge.Electroencephalogram(EEG)can be used as a biomarker to effectively explore depression recognition.Motivated by the studies that multiple smaller scale kernels could increase nonlinear expression compared to a larger kernel,this article proposes a model named the three-dimensional multiscale kernels convolutional neural network model for the depression disorder recognition(3DMKDR),which is a three-dimensional convolutional neural network model with multiscale convolutional kernels for depression recognition based on EEG signals.A three-dimensional structure of the EEG is built by extending one-dimensional feature sequences into a two-dimensional electrode matrix to excavate the related spatiotemporal information among electrodes and the collected electrode matrix.By the major depressive disorder(MDD)and the multi-modal open dataset for mental-disorder analysis(MODMA)datasets,the experiment shows that the accuracies of depression recognition are up to99.86%and 98.01%in the subject-dependent experiment,and 95.80%and 82.27%in the subjectindependent experiment,which are higher than alternative competitive methods.The experimental results demonstrate that the proposed 3DMKDR is potentially useful for depression recognition in older persons in the future.

Association between AKT1 gene polymorphisms and depressive symptoms in the Chinese Han population with major depressive disorder

For this study, 461 Chinese Han patients with depressive disorder were recruited. The AKT1 genotype and allele distribution were determined by PCR amplification and direct sequencing. UNPHASED software was used to analyze associations between the 17-item Hamilton Depression Rating Scale, total score, four factors and the AKT1 rs2494746 and rs3001371 polymorphisms. The results indicate that there is a significant association between suicidal ideation and anxiety symptoms in depressed patients and the rs2494746 polymorphism. The other AKT1 polymorphism, rs3001371, was significantly associated with work and activities. Patients with the rs3001371-A allele had a significantly more severe illness compared to patients with the rs3001371-G allele. Thus, AKT1 polymorphisms appear to be associated with depression severity, anxiety symptoms, work and activities, and suicide attempts in patients with depressive disorder.

Molecular mechanism of noradrenaline during the stress-induced major depressive disorder

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.

Visual impairment and depression: Age-specific prevalence, associations with vision loss, and relation to life satisfaction

BACKGROUND To our knowledge,no study has obtained specific estimates of depression for young and middle-aged adults with visual impairment(VI).As estimates of depression varies across age groups in the general population,it is of interest to examine whether the same applies to adults with low vision or blindness.AIM To estimate depression prevalence and its association with VI-related characteristics and life satisfaction in adults with VI.METHODS A telephone-based cross-sectional survey was conducted between January and May 2017 in an age-stratified sample of adults who were members of the Norwegian Association of the Blind and Partially Sighted.Participants were asked questions about their sociodemographic characteristics,VI characteristics,and life satisfaction.Depression was measured with the Patient Health Questionnaire.The diagnostic scoring algorithm was used to calculate the point prevalence of depression(i.e.,major depression and other depressive disorders)across categories of gender and age(years:18-35,36-50,51-65,≥66).The associations were estimated using regression models.RESULTS Overall,736 adults participated in the study(response rate:61%).The prevalence estimates of depression varied across different age groups,ranging from 11.1%-22.8%in women and 9.4%-16.5%in men,with the highest rates for the two youngest age groups.Results from the multivariable models including sociodemographic and VI-related variables showed that losing vision late in life[Prevalence ratio(PR),1.76,95%CI:1.11,2.79]and having other impairments(PR:1.88,95%CI:1.32,2.67)were associated with higher rates of depression,whereas older age was associated with lower rates(PR:0.83,95%CI:0.74,0.93).Additionally,participants who were depressed had lower life satisfaction than those who were not depressed(adjustedβ:-2.36,95%CI:-2.75,-1.98).CONCLUSION Our findings suggest that depression in adults with VI,and especially among young and middle-aged adults,warrants greater attention by user organisations,clinicians,and healthcare authorities.

Lentivirus-mediated knockdown of phosphodiesterase 4D improved depression-like behaviors in mice

OBJECTIVE To examine whether long-form phosphodiesterase-4(PDE4)knockdown by lentiviral RNA construct containing a speci fi c micro RNA/mi RNAmir hairpin structure reversed depression-like symptoms caused by chronic unpredictable mild stress(CUMS)in mice.METHODS In this research,the study was performed on adult male C57 mice,weighing(25±5)g,kept in a controlled environment.CUMS animal model was used recapitulate a multiple of behavioral characteristics and biochemical states of depression in human.The forced swimming test(FST)and the tail suspension test(TST)were used to detectthe state of depression.Western blotting analysis was used to assess protein levels of c AMP response element binding protein(CREB,unphosphorylated and phosphorylated[p CREB])to explore the neurochemical mechanisms.RESULTS CUMS decreased c AMP levels(P<0.01)and produced depression-like symptoms in FST(P<0.01)and TST(P<0.01).Microinfusions of lentiviruses reversed CUMS-induced c AMP decline(P<0.05)and depression-like symptoms.Moreover,CUMS caused a significant reduction in protein kinase A and CREB phosphorylation,and brain-derived neurotrophic factor transcription,both of which were partially attenuated by lentivirus-mediated knockdown of PDE4D.Also,the phosphorylation of extracellular signal-regulated kinase 1/2 was reduced in CUMS-exposed mice,which was reversed by 4Dmi RNA treatment.Taken together,this study demonstrated that PDE4Dmi RNA improved the CUMS-induced depressionlike symptoms that might be related to the increase in hippocampal c AMP and p CREB expression.CONCLUSION Hence,PDE4D inhibitors can serve as potential antidepressants,and their antidepressant activity is partially mediated by the activation of c AMP signaling pathway in the hippocampus.In other words,long-form PDE4D knockdown may offer a promising treatment for major depression disorder.

Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression,anxiety and psychosis

BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Generalized Anxiety and Major Depressive Symptoms of General Public in South Korea during the Early COVID-19 Pandemic

The extent of viral spread and strategies in dealing with the COVID-19 pandemic have been different in each country.There are overall increased mental health concerns in many countries but it is unclear what the general public individuals who do not have heighten vulnerability to stressors for existing mental diseases or significant physical illnesses were experiencing during the pandemic.We evaluated the stressors and mental health of general public in South Korea that has a relatively low confirmed cases and deaths.Responses on the on-line survey questions were used to assess the mental and physical symptoms in association with individuals’reported stressors.Individuals with the symptoms of the generalized anxiety disorder(GAD)were reported in 58.9%,and major depression(MD)in 23.2%,mostly in minimal to mild degrees,cut-off scores of 5 and 10,respectively by the validated screening tools,GAD-7 and PHQ-9.Both GAD and MD symptoms were in 21.5%of the respondents.The total number of stress had significant association with the scores of GAD-7,PHQ-9,physical symptoms,sleep difficulties and resilience(p<0.01).GAD scores were also associated with sleep difficulties(p<0.01)and raising young children(p<0.05).MD scores were associated with sleep difficulties,job-dissatisfaction,and educational level(p<0.05).The limitations of the study include small sample size,usage of smartphone or email,potential under-reporting by stigma in the socio-cultural context and evolving nature of pandemic.We conclude that keeping careful watch for mental symptoms,stressors,sleep difficulties and other physical symptoms are important even for the individuals without previous mental illnesses during the pandemic era.

Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders

Hippocampus serves as a pivotal role in cognitive and emotional processes,as well as in the regulation of the hypothalamus-pituitary axis.It is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer's disease.Furthermore,dysregulation in the hippocampal function leads to epilepsy and mood disorders.In the first section,we summarized the most salient knowledge on the role of glial cell-line-derived neurotrophic factor and its receptors focused on aging,cognition and neurodegenerative and hippocampal-related neurological diseases mentioned above.In the second section,we reviewed the therapeutic approaches,particularly gene therapy,using glial cell-line-derived neurotrophic factor or its gene,as a key molecule in the development of neurological disorders.In the third section,we pointed at the potential of regenerative medicine,as an emerging and less explored strategy for the treatment of hippocampal disorders.We briefly reviewed the use of partial reprogramming to restore brain functions,non-neuronal cell reprogramming to generate neural stem cells,and neural progenitor cells as source-specific neuronal types to be implanted in animal models of specific neurodegenerative disorders.

How to construct neuroscience-informed psychiatric classification?Towards nomothetic networks psychiatry

Psychiatry remains in a permanent state of crisis,which fragmented psychiatry from the field of medicine.The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic,biological,molecular,pan-omics,precision,cognitive and phenomenological psychiatry,folk psychology,mind-brain dualism,descriptive psychopathology,and postpsychiatry.The current“gold standard”Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach.Therefore,it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches.The aim of this paper is to explain the new nomothetic network psychiatry(NNP)approach,which uses machine learning methods to build data-driven causal models of mental illness by assembling risk-resilience,adverse outcome pathways(AOP),cognitome,brainome,staging,symptomatome,and phenomenome latent scores in a causal model.The latter may be trained,tested and validated with Partial Least Squares analysis.This approach not only allows to compute pathway-phenotypes or biosignatures,but also to construct reliable and replicable nomothetic networks,which are,therefore,generalizable as disease models.After integrating the validated feature vectors into a well-fitting nomothetic network,clustering analysis may be applied on the latent variable scores of the R/R,AOP,cognitome,brainome,and phenome latent vectors.This pattern recognition method may expose new(transdiagnostic)classes of patients which if cross-validated in independent samples may constitute new(transdiagnostic)nosological categories.

Effect of Cognitive Behavioral Therapy Versus Interpersonal Psychotherapy in Patients with Major Depressive Disorder： A Meta-analysis of Randomized Controlled Trials

Background： Practice guidelines have recommended cognitive behavioral therapy （CBT） and interpersonal psychotherapy （IPT） as the treatment of choice for major depression disorder （MDD）. However, whether one therapy is better than the other remains inconclusive. The aim of this study was to compare the treatment efficacy of the two treatment approaches for MDD. Methods： Using the terms ＂cognitive behavior therapy or cognitive therapy or CBTor CTor cognitive behavioral therapy＂ and ＂interpersonal psychotherapy or IPT,＂ we systematically searched PubMed, Psyclnfo and Chinese National Knowledge Infrastructure databases up to February 2017. The language was restricted to be English and Chinese. Therapeutic outcomes, characteristics, and research quality were then extracted and analyzed independently. In accessing the included studies, we followed the criteria suggested by the Cochrane Handbook for Systematic Reviews of Interventions. Results： Data for 946 patients from 10 randomized controlled trials were included in the study. Methodological quality was not optimal in most trials. Meta-analysis showed a mean difference （MD） of -1.31, 95% confidence interval （CI） （-2.49, -0.12） （P 〈 0.05） in favor of CBT according to the Beck Depression Inventory （BDI）, and however, we did not found any statistically significant difference between CBT and IPT on the Hamilton Rating Scale for depression （HRSD） （MD -0.90, 95% CI [-2.18, 0.38]）. Subgroup analyses for the studies in which patients were treated only by psychotherapy （MD -1.26, 95% CI [-2.78, 0.35]） and for those which offered more sessions of therapies （MD -0.82, 95% CI [-2.23, 0.59]） showed there was no significant difference between CBT and IPT according to BDI. Conclusions： Differences in treatment efficacy seem to vary according to different outcome measures. CBT shows an advantage over IPT for MDD according to BDI, and there is no significant difference between the two according to HRSD. These results should be interpreted with caution.

Association between SLC17A7 gene polymorphisms and venlafaxine for major depressive disorder in a Chinese Han population:a prospective pharmacogenetic case-control study

Objective: Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in theSLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder.Methods: This prospective pharmacogenetic case-control study that involved genotyping of four SNPs ofSLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265).Results: The allele and genotype frequencies of the four candidate SNPs inSCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigatedSLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigatedSLC17A7 variants (rs1578944) demonstrated a significant association (P=0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted.Conclusion: No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) inSLC17A7 and venlafaxine treatment in the Chinese Han population.

Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders

The concept of the glial-vascular unit(GVU)was raised recently to emphasize the close associations between brain cells and cerebral vessels,and their coordinated reactions to diverse neurological insults from a“glio-centric”view.GVU is a multicellular structure composed of glial cells,perivascular cells,and perivascular space.Each component is closely linked,collectively forming the GVU.The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system(CNS)disorders have not been elucidated in detail.Here,we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space,which take part in the modulation of cerebral blood flow and angiogenesis,formation of the blood-brain barrier,and clearance of neurotoxic wastes.Next,we discuss dysfunctions of the GVU in various neurological diseases,including ischemic stroke,spinal cord injury,Alzheimer’s disease,and major depression disorder.In addition,we highlight the possible therapies targeting the GVU,which may have potential clinical applications.