Interaction between HTR2A rs3125 and negative life events in suicide attempts among patients with major depressive disorder: a cross-sectional study.

BACKGROUND: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. METHODS: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. RESULTS: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009). CONCLUSION: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD.

Resolving heterogeneity in depression using individualized structural covariance network analysis.

BACKGROUND: Elucidating individual aberrance is a critical first step toward precision medicine for heterogeneous disorders such as depression. The neuropathology of depression is related to abnormal inter-regional structural covariance indicating a brain maturational disruption. However, most studies focus on group-level structural covariance aberrance and ignore the interindividual heterogeneity. For that reason, we aimed to identify individualized structural covariance aberrance with the help of individualized differential structural covariance network (IDSCN) analysis. METHODS: T1-weighted anatomical images of 195 first-episode untreated patients with depression and matched healthy controls (n = 78) were acquired. We obtained IDSCN for each patient and identified subtypes of depression based on shared differential edges. RESULTS: As a result, patients with depression demonstrated tremendous heterogeneity in the distribution of differential structural covariance edges. Despite this heterogeneity, altered edges within subcortical-cerebellum network were often shared by most of the patients. Two robust neuroanatomical subtypes were identified. Specifically, patients in subtype 1 often shared decreased motor network-related edges. Patients in subtype 2 often shared decreased subcortical-cerebellum network-related edges. Functional annotation further revealed that differential edges in subtype 2 were mainly implicated in reward/motivation-related functional terms. CONCLUSIONS: In conclusion, we investigated individualized differential structural covariance and identified that decreased edges within subcortical-cerebellum network are often shared by patients with depression. The identified two subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of depression.

Progressive brain structural abnormality in depression assessed with MR imaging by using causal network analysis.

BACKGROUND: As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown. METHODS: To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis. RESULTS: Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus. CONCLUSIONS: Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.

Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder.

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

The stage-specifically accelerated brain aging in never-treated first-episode patients with depression.

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never-treated first-episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel-based morphometry derived from T1-weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never-treated first-episode patients with depression (N = 195). The brain-predicted age difference (brain-PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age-, gender-, educational level-matched HCs in Dataset 1. Overall, patients presented higher brain-PAD scores suggesting patients with depression having an "older" brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data-driven method and significant correlation between brain-PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage-dependent phenomenon in depression.

Efficacy of simplified-cognitive behavioral therapy for insomnia(S-CBTI) among female COVID-19 patients with insomnia symptom in Wuhan mobile cabin hospital.

BACKGROUND: The outbreak of Coronavirus Disease-2019 (COVID-19) caused great psychological distress often with comorbid insomnia. Insomnia is common in patients with COVID-19 admitted to mobile cabin hospitals. Insomnia may lead to immune dysfunction, a condition not conducive to recovery from COVID-19. The use of sedative-hypnotic drugs is limited by their inhibitory effect on the respiratory system. A paucity of research is available regarding psychotherapy interventions to improve insomnia symptoms among  patients with COVID-19. In the general population, sleep problems are more common in women than in men; insomnia in women patients requires special attention. The aim of this study was to develop simplified-cognitive behavioral therapy for insomnia (S-CBTI) for patients with COVID-19 and comorbid insomnia symptoms and to verify its effectiveness through a self-control trial. A second aim was to compare the effectiveness of S-CBTI between acute and chronic insomnia among women with COVID-19 and comorbid insomnia symptoms in Wuhan Jianghan Cabin Hospital. METHODS: S-CBTI consisted of education on COVID-19 and sleep hygiene, stimulus control, sleep restriction, and self-suggestion relaxation training over a period of two consecutive weeks. Of 67 women, 66 completed psychological intervention and baseline and post-intervention assessments. There were 31 women with acute insomnia and 35 with chronic insomnia. The Insomnia Severity Index (ISI) score and self-compiled sleep data were assessed at baseline and post-intervention, and subjective sleep evaluations were assessed at days 4, 7, 12, and 14. RESULTS: The ISI score, sleep latency, night sleep time, and sleep efficiency were statistically significantlly improved from baseline to post-intervention by paired T-test. After the intervention, the mean ISI score of the acute insomnia group was lower than that of the chronic insomnia group. The reduction of the ISI score and the improvement of sleep time from baseline to post-intervention in the acute insomnia group were greater than those in the chronic insomnia group. Utilization of sedative-hypnotic drugs in the acute insomnia group was less than that in the chronic insomnia group, and the difference was statistically significant. CONCLUSIONS: S-CBTI can improve the insomnia symptoms of women with COVID-19 in mobile cabin hospitals, especially for stress-related acute insomnia.

Association between T-182C, G1287A polymorphism in NET gene and suicidality in major depressive disorder in Chinese patients.

Objective: Previous studies have implicated norepinephrine transporter gene (NET) polymorphisms in the etiology of major depressive disorder (MDD). A functional NET T-182C polymorphism (rs2242446) in the promoter region and a synonymous polymorphisms G1287A in the exon 9 (rs5569) were associated with MDD in different populations. However, few studies have focused on the relationship between these polymorphisms and MDD patients with suicidality. The objective of the present study was to examine whether the two polymorphisms are associated with MDD patients with suicidality in the Han Chinese population. Methods: Two hundred and sixty-three suicidal depressed patients and 241 non-suicidal depressed patients who met DSM-IV criteria for MDD were recruited from our hospital. Three hundred and three unrelated, age- and sex-matched healthy control subjects participated in this case-control study. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton rating scale for depression (HAMD). Genotypes of T-182C polymorphism (rs2242446) and G1287A (rs5569) were screened by polymerase chain reaction. Results: No statistical significant differences between patients and controls were found for any of the analysed polymorphisms, either in the genotype or allele distribution. Conclusions: Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of MDD with suicidality. However, the results must be verified in larger samples and different ethnicities.

Chronic Fluoxetine Treatment Upregulates the Activity of the ERK1/2-NF-κB Signaling Pathway in the Hippocampus and Prefrontal Cortex of Rats Exposed to Forced-Swimming Stress.

OBJECTIVES: The aim of this study was to explore whether or not the antidepressant actions of fluoxetine (FLX) are correlated with extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor κ-light chain enhancer of activated B cells (NF-κB) in the hippocampus (HC) and prefrontal cortex (PFC) of rats. MATERIALS AND METHODS: A total of 108 male Sprague-Dawley rats were randomly divided into 6 groups of 18 rats each. Group 1 was the control group, while group 2 comprised the depressed model in which rats were subjected to 28 days of forced-swimming stress (FST); groups 3-6 were also subjected to 28 days of FST and treated with FLX once a day for 1 day (group 3; F1d), 1 week (group 4; F1w), 2 weeks (group 5; F2w), or 4 weeks (group 6; F4w). The control group was not subjected to FST or treated with FLX. Behavior tests that included the Morris water maze (MWM) and saccharin preference were performed, and ERK1/2 and NF-κB proteins were assayed using Western blot. RESULTS: The rats in the control group and in groups 5 and 6 (F2w and F4w, respectively) had a significantly shorter average escape latency, needed more attempts in order to successfully cross the platform, and had a greater saccharin preference than those in the depressed group (p < 0.05). In the depressed group, the phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated NF-κB (p-NF-κB) expression in the HC and PFC were lower than in the control group (p < 0.05). Treatment with FLX reversed the changes in the expression of p-ERK1/2 and p-NF-κB in rats in the F2w and F4w groups. CONCLUSIONS: In this study, FLX treatment for 2 weeks or longer reversed the impaired spatial learning, memory, and anhedonia observed in the depressed model rats and upregulated the activities of the ERK1/2-NF-κB signaling pathway.

Association study between 5-HT2A and NET gene polymorphisms and recurrent major depression disorder in Chinese Han population.

A functional NET T-182C polymorphism (rs2242446) in the promoter region, a synonymous polymorphisms G1287A in the exon 9(rs5569) and a functional serotonin 2A (5-HT2A) receptor (rs6311) genes in the promoter region were associated with MDD in different populations. However, few studies have focused on the relationship between these three polymorphisms and recurrent MDD patients in Chinese Han population. Three hundred MDD patients (112 males, 188 females) and three hundre unrelated healthy controls were enrolled in the study. POST-PCR ligase detection reaction genotype assay method was used for the genotypic analyses. There existed significant differences both in the frequencies of alleles and genotypes between patients and controls for the 5-HT2A receptor gene polymorphism (χ2=9.267, p=0.01 for genotype; χ2=7.615,p=0.006 for allele). No difference in genotype and allele distribution of G1287A, T182C were found in MDD patients and controls. Our results suggest that the rs6311 polymorphism seems to be the susceptibility factor in etiology of recurrent MDD. In conclusion, 5-HT2A receptor gene variants may be involved in the etiology of MDD, although the results must be verified in larger samples and different ethnicities.

Identifying two distinct neuroanatomical subtypes of first-episode depression using heterogeneity through discriminative analysis.

BACKGROUND: Neurobiological heterogeneity in depression remains largely unknown, leading to inconsistent neuroimaging findings. METHODS: Here, we adopted a novel proposed machine learning method ground on gray matter volumes (GMVs) to investigate neuroanatomical subtypes of first-episode treatment-naïve depression. GMVs were obtained from high-resolution T1-weighted images of 195 patients with first-episode, treatment-naïve depression and 78 matched healthy controls (HCs). Then we explored distinct subtypes of depression by employing heterogeneity through discriminative analysis (HYDRA) with regional GMVs as features. RESULTS: Two prominently divergent subtypes of first-episode depression were identified, exhibiting opposite structural alterations compared with HCs but no different demographic features. Subtype 1 presented widespread increased GMVs mainly located in frontal, parietal, temporal cortex and partially located in limbic system. Subtype 2 presented widespread decreased GMVs mainly located in thalamus, cerebellum, limbic system and partially located in frontal, parietal, temporal cortex. Subtype 2 had smaller TIV and longer illness duration than Subtype 1. And TIV in Subtype 1 was positively correlated with age of onset while not in Subtype 2, probably implying the different potential neuropathological mechanisms. LIMITATIONS: Despite results obtained in this study were validated by employing another brain atlas, the conclusions were acquired from a single dataset. CONCLUSIONS: This study revealed two distinguishing neuroanatomical subtypes of first-episode depression, which provides new insights into underlying biological mechanisms of the heterogeneity in depression and might be helpful for accurate clinical diagnosis and future treatment.

Cost-utility analysis of using paliperidone palmitate in schizophrenia in China.

Objective: Long-acting injections (LAIs) of paliperidone palmitate have been shown to improve medication adherence and relieve psychotic symptoms. However, the specific cost-utility analysis of these LAIs in schizophrenia in China remains unclear. Methods: A multi-state Markov model was constructed to simulate the economic outcomes of patients with schizophrenia in China who received paliperidone palmitate 1-month formulation (PP1M), paliperidone palmitate 3-month formulation (PP3M), and paliperidone extended-release (ER). A cost-utility analysis was conducted, mostly derived from published literature and clinical databases. All costs and utilities were discounted at a rate of 5% per annum. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were also applied. Results: After 20 years, compared to ER, using PP1M resulted in an increased discounted cost from $36,252.59 to $43,207.28. This increased cost was associated with a gain in quality-adjusted life years (QALYs) from 8.60 to 9.45. As a result, the ICER for PP1M was estimated to be $8,247.46/QALY, which was lower than the willingness-to-pay (WTP) threshold of $12,756.55/QALY. When using PP3M instead of ER, the incremental cost was $768.81 and the incremental utility was 0.88 QALYs, projecting an ICER of $873.13/QALY, which was also lower than the WTP threshold of $12,756.55/QALY. The univariate sensitivity analysis showed that the costs of PP1M, PP3M, and ER had the greatest impact on ICERs. The probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,756.55/QALY, the probability of PP1M and PP3M being cost-effective was 59.2% and 66.0%, respectively. Conclusion: From the Chinese healthcare system perspective, PP3M and PP1M are both more cost-effective compared to ER, and PP3M has notable cost-utility advantages over PP1M.

Anxiety during the COVID-19 pandemic in prisoners who had high risks to suffer from mood disorders: A longitudinal study before and during the COVID-19.

We compared the anxiety levels in prisoners before and after the COVID-19 outbreak and analyzed the causes of the changes in anxiety. The first survey was conducted in October 2019 (T0), and the second was conducted in March 2020 (T1). Generalized anxiety disorder-7 (GAD-7), Patient Health Questionnaire-9, and Insomnia Severity Index scales were selected to assess the quality of emotion and sleep among prisoners (N = 803). Three subjective questions were asked to evaluate prisoners' personal feelings on the COVID-19. Paired Samples T-test, Binary, and Multivariate Logistic Stepwise Regression were used to analyze the data. GAD-7 scores decreased at T1 (p < 0.001). For the prisoners without anxiety at T0 (n = 480), GAD-7's mean value at T1 raised (p < 0.001), whereas the mean value decreased (p < 0.001) for the prisoners with anxiety at T0 (n = 323). For the prisoners without anxiety, shorter years of education (OR = 0.843), COVID-19 (OR = 4.936), severer depression at T1 (OR = 1.683), and severer insomnia at T1 (OR = 1.134) were associated with the new onset of anxiety. For the prisoners with anxiety, anxiety was alleviated in 71.2% and exacerbated in 10.5% at T1. For the alleviators, severer depression at T1 (OR = 0.667) and COVID-19 (OR = 0.258) were associated with anxiety unrelief; severer anxiety at T0 (OR = 1.343) was associated with anxiety alleviation. For the exacerbators, severer anxiety at T0 (OR = 0.517) was associated with anxiety unaggravation; severer depression at T1 (OR = 1.196), COVID-19 (OR = 22.882), and severer depression at T0 (OR = 1.181) were associated with anxiety exacerbation. At the outbreak of COVID-19, prisoners' anxiety was reduced. The main factor was the baseline anxiety levels. That may be related to prison management and the Downward Social Comparison.

Convergent molecular and structural neuroimaging signatures of first-episode depression.

BACKGROUND: Convergent studies have demonstrated morphological abnormalities in various brain regions in depression patients. However, the molecular underpinnings of the structural impairments remain largely unknown, despite a pressing need for treatment targets and mechanisms. Here, we investigated the gray matter volume (GMV) alteration in patients with depression and its underlying molecular architecture. METHODS: We recruited 195 first-episode, treatment-naïve depression patients and 78 gender-, age-, and education level-matched healthy controls (HCs) who underwent high-resolution T1-weighted magnetic resonance scans. Voxel-based morphometry (VBM) was adopted to calculate the GMV differences between two groups. Then we analyzed the spatial correlation between depression-induced alteration in GMV and density maps of 10 receptors/transporters deriving from prior molecular imaging in healthy people. RESULTS: Compared to HCs, the depression group had significantly increased GMV in the left ventral portions of the ventral medial prefrontal cortex, parahippocampal gyrus, amygdala, the right superior parietal lobule and precuneus while decreased GMV in the bilateral hippocampus extending to the thalamus and cerebellum. The GMV alteration introduced by depression was spatially correlated with serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2) and GABAergic receptor (GABAa) densities. LIMITATIONS: The conclusions drawn in this study were obtained from a single dataset. CONCLUSIONS: This study reveals abnormal GMV alteration and provides a series of neurotransmitters receptors possibly related to GMV alteration in depression, which facilitates an integrative understanding of the molecular mechanism underlying the structural abnormalities in depression and may provide clues to new treatment strategies.

Altered structural covariance network of nucleus accumbens is modulated by illness duration and severity of symptom in depression.

The differential structural covariance of nucleus accumbens (NAcc), playing a vital role in etiology and treatment, remains unclear in depression. We aimed to investigate whether structural covariance of NAcc was altered and how it was modulated by illness duration and severity of symptom measured with Hamilton Depression scale (HAMD). T1-weighted anatomical images of never-treated first-episode patients with depression (n = 195) and matched healthy controls (HCs, n = 78) were acquired. Gray matter volumes were calculated using voxel-based morphometry analysis for each subject. Then, we explored abnormal structural covariance of NAcc and how the abnormality was modulated by illness duration and severity of symptom. Patients with depression exhibited altered structural covariance of NAcc connected to key brain regions in reward system including the medial orbitofrontal cortex, amygdala, insula, parahippocampa gyrus, precuneus, thalamus, hippocampus and cerebellum. In addition, the structural covariance of the NAcc was distinctly modulated by illness duration and the severity of symptom in patients with depression. What is more, the structural covariance of the NAcc connected to hippocampus was modulated by these two factors at the same time. These results elucidate altered structural covariance of the NAcc and its distinct modulation of illness duration and severity of symptom.

Reliability and validity of the brief psychosomatic symptom scale (BPSS) in patients from general hospitals.

OBJECTIVES: To verify the Brief Psychosomatic Symptom Scale (BPSS) among patients with psychosomatic-related disorders in general hospitals and determine the threshold of BPSS. METHODS: The BPSS is a shortened 10-item version of the psychosomatic symptoms scale (PSSS). Data from 483 patients and 388 healthy controls were included for psychometric analyses. Internal consistency, construct validity, and factorial validity were verified. The threshold of BPSS in distinguishing psychosomatic patients from healthy controls were determined using receiver operating characteristic (ROC) curve analysis. The ROC curve of the BPSS was compared with that of the PSSS and patient health questionnaire-15 (PHQ-15) by using Venkatraman's method with 2000 times Monte-Carlo simulations. RESULTS: The reliability of the BPSS was good with Cronbach's α of 0.831. BPSS was significantly correlated with PSSS (r = 0.886, P < 0.001), PHQ-15 (r = 0.752, P < 0.001), PHQ-9 (r = 0.757, P < 0.001) and GAD-7 (r = 0.715, P < 0.001), which indicated good construct validity. ROC analyses demonstrated that the AUC of the BPSS was comparable with that of PSSS. The gender-specific threshold of BPSS was determined as ≥8 in males and ≥ 9 in females. CONCLUSIONS: The BPSS is a brief and validated instrument for screening common psychosomatic symptoms.

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.

BACKGROUND: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD). METHODS: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated. RESULTS: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%). LIMITATIONS: A short-term non-inferiority study without a placebo arm. CONCLUSIONS: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

C-reactive protein could predict the efficacy of SSRIs in clinical practice: A cohort study of large samples in the real world.

BACKGROUND: C-reactive protein (CRP) has been shown to predict antidepressant treatment outcomes in several trials, but they were limited to small-sample and strictly-restricted conditions. This study plans to verify if CRP can predict antidepressant efficacy in large samples in the real world. METHODS: 918 depressed patients who had tested CRP were included, then were followed up through their outpatient visits or by telephone to obtain information about their medication therapy (SSRIs, SNRIs, MT, NaSSA) and assess efficacy using the Clinical Global Impressions-Improvement scale (CGII). Efficacy was classified as effective and ineffective and CRP was separated into the low CRP group (CRP <1 mg/L, n = 709) and the high CRP group (CRP ≥1 mg/L, n = 209).The efficacy was compared in different groups. RESULTS: Using Kaplan-Meier survival analysis and Cox proportional regression model to analyze, it was discovered that SNRIs were more effective than SSRIs in treating patients with high CRP(HR = 1.652, p = 0.037,95 % CI:1.031-2.654), and SSRIs were more effective in treating patients with low CRP than those with high CRP (HR = 1.257, p = 0.047,95 % CI:1.003-1.574), while no difference in efficacy between the two groups was found in patients using SNRIs, MT, NaSSA. LIMITATIONS: Small amounts of MT and NaSSA were included, and some factors that may affect CRP value have not been controlled. CONCLUSION: CRP could predict the efficacy of SSRIs in the real world, depressed patients with high CRP may be more likely to respond poorly to SSRIs.

TNF-α (G-308A) Polymorphism, Circulating Levels of TNF-α and IGF-1: Risk Factors for Ischemic Stroke-An Updated Meta-Analysis.

Objective: Accumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-α gene promoter region and increased levels of TNF-α were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-α and IGF-1 with IS in different ethnic backgrounds and different sourced specimens. Methods: In this study, we examined whether rs1800629 genetic variant and levels of TNF-α and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria. Results: A total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS pathogenesis. Conclusion: Our findings demonstrated that the TNF-α rs1800629 polymorphism, the increased levels of TNF-α, and decreased levels of IGF-1 were involved in the etiology of IS.

Correlation between Aß1-42, Dnmt3a2, urinary AD7c-NTP and cognitive dysfunction in first-episode and recurrent MDD: A case-control study.

Background and Aim: Major depressive disorder (MDD) is one of the most prevalent mental illnesses worldwide and involves cognitive dysfunction that may negatively impact clinical and social outcomes. Previous studies have suggested that beta-amyloid peptide (Aß1-42), DNA methyltransferase (Dnmt3a2), and urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) are associated with cognitive impairment. However, there are no relevant studies in MDD. The aim of this study was to assess the correlation between serum Aß1-42, Dnmt3a2, and urinary AD7c-NTP and cognitive dysfunction in MDD. Materials and Methods: A total of 59 eligible patients were included in the study, including 29 patients with first-episode MDD (FEDs) and 30 patients with recurrent MDD (RMDDs), and 30 matched healthy controls (HCs) were selected. Participants' cognitive functioning was evaluated using the MATRICS consensus cognitive battery (MCCB). The enzyme-linked immunosorbent assay (ELISA) method was used to measure the concentrations of the three proteins. Statistical analysis was completed using Statistical Package for the Social Sciences (SPSS) 20.0. The statistical significance was set as P < 0.05. Results: Serum Dnmt3a2 and urinary AD7c-NTP showed significant differences among the three groups (both P < 0.001), but there were no significant differences in Aß1-42 levels. Upon examining the results of cognitive testing, we found that serum Aß1-42 was negatively associated with working memory scores in RMDDs (P = 0.020), but Dnmt3a2 was positively associated with working memory and verbal learning scores in the same cohort (P = 0.012 and P = 0.037, respectively). In contrast, urinary AD7c-NTP was negatively correlated with verbal learning scores in FEDs (P = 0.013). Conclusions: Serum Dnmt3a2 and Aß1-42 levels may be associated with cognitive impairment in RMDDs and may act as potential biomarkers of cognitive impairment. Although urinary AD7c-NTP was closely related to cognitive dysfunction in FEDs, this relationship did not hold in RMDDs.

Integrative Functional, Molecular, and Transcriptomic Analyses of Altered Intrinsic Timescale Gradient in Depression.

The pathophysiology and pharmacology of depression are hypothesized to be related to the imbalance of excitation-inhibition that gives rise to hierarchical dynamics (or intrinsic timescale gradient), further supporting a hierarchy of cortical functions. On this assumption, intrinsic timescale gradient is theoretically altered in depression. However, it remains unknown. We investigated altered intrinsic timescale gradient recently developed to measure hierarchical brain dynamics gradient and its underlying molecular architecture and brain-wide gene expression in depression. We first presented replicable intrinsic timescale gradient in two independent Chinese Han datasets and then investigated altered intrinsic timescale gradient and its possible underlying molecular and transcriptional bases in patients with depression. As a result, patients with depression showed stage-specifically shorter timescales compared with healthy controls according to illness duration. The shorter timescales were spatially correlated with monoamine receptor/transporter densities, suggesting the underlying molecular basis of timescale aberrance and providing clues to treatment. In addition, we identified that timescale aberrance-related genes ontologically enriched for synapse-related and neurotransmitter (receptor) terms, elaborating the underlying transcriptional basis of timescale aberrance. These findings revealed atypical timescale gradient in depression and built a link between neuroimaging, transcriptome, and neurotransmitter information, facilitating an integrative understanding of depression.