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The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini‐International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19–2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. Methods: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10–20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions—Severity (CGI-S) scores, respectively. Results: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were − 33.6 for the AOM group and − 34.8 in the oral aripiprazole group, respectively, with a difference of − 1.2 (95% CI: − 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was − 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was − 2.2 and − 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. Conclusions: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. Trial registration: ClinicalTrials.gov identifier: NCT03172871. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers. Methods: We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status. Results: Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. Conclusions: Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors. [ABSTRACT FROM AUTHOR]

Background: Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method: Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results: We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD. Conclusions: In Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Serotonin transporter (5-HTT) and 5-HT receptor (5-HTR) involved in the neurotransmission of 5-HT may play an important role in the development of major depression disorder (MDD). Several lines of evidence suggested that the gene–environment interaction may confer susceptibility to depression. The aim of this study is to analyze the combined effect of four serotonin-related genes and two environmental factors on MDD in a Chinese population. Methods: This study recruited a total of 401 patients with MDD and 391 age- and gender-matched control subjects. They were all Chinese Han origin. Negative life events and objective social supports were assessed using standard rating scales. Six polymorphisms in the four serotonin-related genes (5-HTT, 5-HTR1A, 5-HTR1B and 5-HTR2A) were selected to detect. The analyses of the gene–environment interactions were performed by the Multifactor Dimensionality Reduction (MDR). Results: Allelic associations between patients with MDD and controls were observed for the polymorphism of 5-HTTLPR and for rs6295 at the 5-HTR1A locus. The 5-HTTLPR polymorphism was associated with negative life events on MDD. A three-way interaction between the 5-HTTLPR polymorphism, rs6295 and negative life events on MDD was found in the individuals aged from 20 years to 29 years. In addition, the individuals carrying the L/L genotype of 5-HTTLPR could be susceptible to MDD when exposed to negative life events. Conclusions: The 5-HTTLPR polymorphism may modify the interaction between negative life events and MDD in the Chinese population. To our knowledge, this is the first report on the combined effect for the 5-HTTLPR polymorphism and 5-HTR1A genes on modifying the response to negative life events conferring susceptibility to MDD in the 20–29 year group. [Copyright &y& Elsevier]

The aim of the present study was to detect the combined effect of negative life events and the norepinephrine transporter (NET) gene on the development of major depression (MD) in a Chinese population. We recruited 388 unrelated patients affected with MD and 388 healthy controls in this study. The score of 32 was used as a cut-off value for grouping the negative life events into the severe and moderate forms using the Life Events Scale (LES). SNPs including rs2242446 and rs5569 of the NET gene were genotyped. The chi-square ( χ 2) test showed allelic association for the T-182C polymorphism ( χ 2 = 6.46, corrected P = 0.011) and also showed genotypic association ( χ 2 = 6.87, corrected P = 0.034). Multifactor dimensionality reduction (MDR) showed that the interaction between the rs2242446–rs5569 combination and negative life events had a CV consistency of 10 and PE of 0.3487. Compared with those having both T-G-MN combination used as reference group, we found that the OR scaled up from 1 to 7.39 (95%CI 3.40–16.06) in the C-A-SN group. The present study suggests that the combined effect of rs2242446 and rs5569 in the NET gene could modify the response to the negative life events in triggering MD. [ABSTRACT FROM AUTHOR]

This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients. • Group heterogeneity existed in the depression trajectories of Chinese MDD patients. • Histories of cardiovascular disease appear as a risk factor for unfavorable courses. • Poorer response for initial treatment also appears as a potential risk factor. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between psychosocial variables and depression severity among Chinese patients with first-episode major depressive disorder (MDD).Methods: This multicenter case-control study enrolled patients with first-episode MDD and healthy controls (HCs) from nine sites in China. Depressive symptoms, clinical features, and psychosocial variables were evaluated. Based on the total score of the Hamilton Rating Scale of Depression (HRSD-17), patients with MDD were classified into three subgroups of severity (mild, moderate and severe). The logistic regression analyses were conducted to investigate the independent risk factors of MDD and different severities of depression.Results: Overall, 598 MDD patients and 467 HCs were included. The proportions of patients with mild, moderate, and severe depression were 260 (29.5%), 443 (50.2%), and 179 (20.3%), respectively. The logistic regression model revealed that the demographic and psychosocial factors could explain 50.6% of the total variance of occurrence of MDD in the whole sample with HCs. However, in the subsample of MDD patients, only older age [OR=1.03 (95%CI: 1.02-1.05)], stressful social events [OR=1.04 (95%CI: 1.02-1.06)], and melancholic feature [OR=2.68 (95%CI: 1.91-3.74)] were independent risk factors for moderate and severe depression; these factors combined to explain only 10.2% of the total variance.Limitations: Only patients with first-episode MDD were included in this study, leaving the associated factors for the severity of recurrent depression uninvestigated.Conclusion: Demographic and psychosocial variables had satisfactory performance in predicting the occurrence of MDD, but showed inadequate value in predicting the depression severity of MDD patients. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown that microRNAs(miRNAs) are involved in the pathogenesis of MDD; in particular, miR-34b/c has been implicated in MDD risk and found to exert antidepressant effects. However, the effects of miR-34b/c polymorphisms on MDD risk have not been investigated. Methods In this study, we evaluated the effect of miR-34b/c gene polymorphisms and their interaction with negative life events in relation to MDD, using data from 381 Han Chinese patients with MDD and 291 healthy volunteers. Allelic, genotypic, haplotypic, and gene-environment associations were analyzed using UNPHASED and SPSS software. Results After discarding data with extremely severe negative life events in our study population, we found an association between rs4938723, rs2187473 polymorphisms and MDD in the dominant models (TC/CC vs. TT, OR = 1.45, P = 0.027; TC/CC vs. TT, OR = 3.32, P = 0.030). In haplotype analysis, the C-G haplotype (rs4938723/rs28757623) showed the strongest association with MDD (OR = 1.95, P = 0.026). Additionally, we found significant gene-environment combination rs4938723 C allele, rs28757623 G allele and high level of negative life events (C-G-HN) was significantly associated with MDD (OR, 3.85; 95% CI, 1.62–9.13). In addition, the combination of (C-C-HN) is of significance (OR, 2.99; 95% CI, 1.36–6.60), indicating that the rs28757623 C allele may contribute to the risk of MDD as well. Limitations The sample size was small and the role of miR-34b/c polymorphisms for MDD should be assessed using independent samples from other ethnic populations. Conclusions: Our results suggest that miR-34b/c is a susceptibility factor for MDD stratified by negative life events and that rs4938723 is a significant association locus for gene-environment interaction in relation to MDD risk. [ABSTRACT FROM AUTHOR]

Abstract: The norepinephrine transporter (NET), which is involved in the neurotransmission of norepinephrine (NE), may play an important role in the development of major depressive disorder (MDD). Recent studies have suggested that a gene–environment interaction may confer susceptibility to depression. The aims of this study were to test modifying effects of the NET gene on the association between residency and MDD, as well as to reveal the relationship between gender and this gene-environment interaction in MDD. This study recruited a total of 442 patients with MDD and 393 controls. Residence was defined as reported in the data of the 5th Chinese census. Logistic regression models were used to analyze gene–environment interactions. A gene–environment interaction between the G1287A polymorphism and residency was found in the female sample. In addition, and odds ratio analysis showed that only rural women carrying the G/G genotype of the G1287A polymorphism were susceptible to MDD, but others were not. To our knowledge, this is the first report showing that the G1287A polymorphism modifies rural residency as a risk factor for MDD. These findings support the possibility that the NET gene is an important factor in susceptibility to MDD in a Han Chinese population. [Copyright &y& Elsevier]