Major depressive disorder (MDD), also referred to as depression, is one of the most common psychiatric disorders with a high economic burden. The etiology of depression is still not clear, but it is ...generally believed that MDD is a multifactorial disease caused by the interaction of social, psychological, and biological aspects. Therefore, there is no exact pathological theory that can independently explain its pathogenesis, involving genetics, neurobiology, and neuroimaging. At present, there are many treatment measures for patients with depression, including drug therapy, psychotherapy, and neuromodulation technology. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in the clinic. This article mainly reviews the research progress, pathogenesis, and treatment of MDD.
Rationale
The rapid-onset and long-lasting antidepressant properties of ketamine have prompted investigations into a variety of agents that target N-methyl-D-aspartate receptors (NMDARs) for the ...treatment of major depressive disorder (MDD). According to the literature, ifenprodil (a GluN2B-containing NMDAR antagonist) can potentiate the antidepressant-like effects of certain antidepressant drugs in mice. Here, we report that a single injection of ifenprodil (3 mg/kg, intraperitoneally (i.p.)) was sufficient to provoke rapid antidepressant-like effects in chronic unpredictable mild stress (CUMS) rats. Moreover, ifenprodil activated mTOR signaling and reversed the CUMS-induced elevation of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampus after acute administration. Unfortunately, in our study, ifenprodil had no influence on corticosterone levels in the plasma. Our data indicate that ifenprodil per se might exert antidepressant-like effects by modulating neuroplasticity and inflammatory processes rather than the typical hormonal factors affected by stressors.
Objectives
To explore the potential rapid antidepressant-like effects and mechanisms of ifenprodil, a GluN2B subunit-selective NMDAR antagonist.
Methods
Male Sprague-Dawley rats were used in 3 separate experiments. In experiment 1, we used the forced swim test (FST) and sucrose preference test (SPT) to identify the rapid antidepressant-like effects of ifenprodil in chronic unpredictable mild stress (CUMS) rats after acute administration. In experiment 2, we assessed neurochemical changes involved in synaptic plasticity within the hippocampus of CUMS rats. In experiment 3, we assessed the levels of corticosterone in the plasma and proinflammatory cytokines in the hippocampus in CUMS rats after ifenprodil treatment.
Results
Ifenprodil rapidly ameliorated depressive-like behaviors in the FST and SPT, activated mTOR signaling, dephosphorylated eukaryotic elongation factor 2, enhanced BDNF expression, and promoted the synthesis of the synaptic protein GluA1 synthesis after acute administration. Moreover, ifenprodil reversed the CUMS-induced elevation of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampus after acute administration. Unfortunately, ifenprodil had no influence on corticosterone levels in the plasma in our study.
Conclusions
Our data indicate that ifenprodil per se might exert antidepressant-like effects through its effects on neuroplasticity and inflammatory processes rather than the typical hormonal factors affected by stressors.
Suicide risk is greatly increased in depression. Detection of those at risk is clinically important. Hence, this study aimed to evaluate the prevalence and identify independent risk factors ...associated with suicidal ideation (SI) in a widespread symptomatology within and outside DSM framework.
This study was part of the National Survey on Symptomatology of Depression (NSSD) which was designed to investigate the magnitude of symptoms of current major depressive episode in China. Stepwise multivariable logistic regression was performed to examine the independent risk factors for SI, including variables that are statistically significant in univariate analysis. Receiver operating characteristic (ROC) was used to evaluate the performance of the regression model.
A total of 3275 patients (1293 males and 1982 females) were included in our analysis. Of these, 1750 patients (53.4%) had SI. Independent risk predictors included crying (P = 0.000; odds ratio = 1.827), helplessness (P = 0.000; odds ratio = 1.514), worthlessness (P = 0.001; odds ratio = 1.359), hopelessness (P = 0.000; odds ratio = 1.805), unusually restless (P = 0.005; odds ratio = 1.276), self-harm (P = 0.000; odds ratio = 3.385), mood-incongruent psychosis (P = 0.000; odds ratio = 2.782), feeling losing control of oneself (P = 0.009; odds ratio = 1.352), hypersomnia (P = 0.000; odds ratio = 1.805), sensory system complaints (P = 0.000; odds ratio = 1.546), derealization (P = 0.006; odds ratio = 1.580), guilt (P = 0.002; odds ratio = 1.332), suicidal attempts (P = 0.000; odds ratio = 2.841), male gender (P = 0.001; odds ratio = 0.756), the total course of depression (P = 0.010; odds ratio = 1.003) in the regression model. In addition, the areas under the curve of the ROC and the accuracy for the regression model were 0.80 and 0.76, respectively.
This study provided an effective risk model for SI in MDD and indicated that all these factors in our model allow better the employment of preventative measures.
•Chinese patients with first-episode major depressive disorder have a high risk to elicit suicidal ideation.•No gender difference in the incidence of suicidal ideation were found in present ...study.•Patients with more somatic symptoms would have the higher risk of suicidal ideation.•Younger patients were more likely to express suicidal thoughts.•Somatic symptoms like pre-verbal physical complaints, sensory system complaints, other pain conditions, late insomnia, hypersomnia, weight loss, hyposexuality were strongly associated with current SI in first-episode Chinese major depression.
Somatic symptoms are prevalent in patients with major depressive disorder (MDD) and often associated with a high risk of suicide. However, which somatic symptoms display as significant risk factors for suicidal ideation (SI) is still poorly understood in MDD.
Two thousand and seventeen Chinese patients with first-episode MDD from the National Survey on Symptomatology of Depression were included in this study. A doctor-rating assessment questionnaire was constructed to evaluate depression related somatic symptoms, and stepwise logistic regression analysis was performed to explore the relationship between somatic symptoms and SI.
Our results showed a high prevalence of current SI in first-episode MDD (50.87%), while no significant gender differences (53.32% vs. 49.26%, P = 0.076) were observed. In addition, patients who have more somatic symptoms would be at the higher risk to elicit SI, and stepwise logistic regression analysis indicated that age (β = -0.020, P < 0.001), Pre-verbal physical complaints (β = 0.356, P = 0.001), Sensory system complaints (β = 0.707, P = 0.000), Other pain conditions (β = 0.434, P < 0.001), Late insomnia (β = 0.267, P = 0.008), Hypersomnia (β = 0.936, P < 0.001), Weight loss (β = 0.272, P = 0.006), Hyposexuality (β = 0.513, P = P < 0.001) were strongly associated with current SI in first-episode Chinese major depression.
Somatic symptoms are strongly associated with SI in first-episode MDD. It is suggestive for clinicians to show concerns for patients' somatic symptoms in practice.
Background:
Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which ...integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).
Methods:
Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review.
Results:
All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (standardized mean differences SMDs ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than the placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (odds ratios ORs ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250–350mg daily) had significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250–350mg daily).
Conclusions:
All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects.
Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism ...underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a mediator for chronic stress-induced depression-like behaviors and neuronal atrophy in mice. One-month chronic restraint stress (CRS) up-regulated PTEN signaling pathway in the PFC of mice as indicated by increasing levels of PTEN, p-MEK, and p-ERK but decreasing levels of p-AKT. Over-expression of Pten in the PFC led to an increase of depression-like behaviors, whereas genetic inactivation or knockdown of Pten in the PFC prevented the CRS-induced depression-like behaviors. In addition, systemic administration of PTEN inhibitor was also able to prevent these behaviors. Cellular examination showed that Pten over-expression or the CRS treatment resulted in PFC neuron atrophy, and this atrophy was blocked by genetic inactivation of Pten or systemic administration of PTEN inhibitor. Furthermore, possible causal link between Pten and glucocorticoids was examined. In chronic dexamethasone (Dex, a glucocorticoid agonist) treatment-induced depression model, increased PTEN levels were observed, and depression-like behaviors and PFC neuron atrophy were attenuated by the administration of PTEN inhibitor. Our results indicate that PTEN serves as a key mediator in chronic stress-induced neuron atrophy as well as depression-like behaviors, providing molecular evidence supporting the synaptic plasticity theory of depression.
To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar ...II (BP-II) disorder who were misdiagnosed as having MDD .
The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses.
A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD .
The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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