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A correction to this paper has been published: https://doi.org/10.1007/s12264-021-00694-9.
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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.
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Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.
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Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.
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Objective To explore the relationship among depression,anxiety and social support in elderly patients in community outpatient clinic. Methods A total of 551 elderly outpatients from two com-munity health service centers of Hongkou District in Shanghai were evaluated with patient health question-naire-9 (PHQ-9),generalized anxiety disorder-7 (GAD-7),perceived social support scale( PSSS) for de-pression,anxiety,physical health and social support. Results The prevalence rates of depression and anxiety were 26. 1% and 17. 2%,respectively. The scores of PHQ-9 and GAD-7 were 2. 0(4. 0) and 1. 0(2. 0). There were statistically significant differences in the scores of family support,friend support,other support and social support among the elderly patients with different degrees of depression or anxiety (P<0. 01). Fam-ily support(B=-0. 196) and friend support(B=-0. 171) were protective factors of depression in elderly pa-tients in community outpatient clinic. Age,family support and friend support were protective factors of anxiety in elderly patients,while gender and fluctuation of physical diseases were protective factors of anxiety(P<0. 05). Con-clusions The depression and anxiety is intimately related to social support in elderly outpatients. Appropriate measures should be taken to optimize social support,mitigate bad mood negative improve their quality of life.
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Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder Ⅰ (BD-Ⅰ),and to elucidate the relationship between the use of different mood stabilizers and brain structure variations.Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-Ⅰ and 30 healthy controls(HC).The patients were divided into BD-Ⅰ with lithium group and BD-Ⅰ with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA.Results Compared with HC,BD-Ⅰ patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI (x,y,z):2,34,-18),orbital frontal cortex (MNI(x,y,z):-32,22,-4),frontal operculum (MNI(x,y,z):38,18,4) and insula cortex (MNI(x,y,z):-32,22,-4) (P＜0.05).There was no significant difference in thevolume of gray matter between BD-Ⅰ with lithium group and BD-Ⅰ with valproate group(P＞0.05).Conclusion Emotional disturbance in patients with BD-Ⅰ may be associated with reduced gray matter volume in the medial frontal cortex,orbital frontal cortex,frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-Ⅰ.
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Objective · To detect the vitamin D2 and D3 levels in the patients with moderate and severe depression. Methods · Eighty-five patientswho met the criteria for major depressive disorder were recruited (53 patients with moderate depression, 32 patients with severe depression). Fifty agematchedhealthy volunteers were recruited as controls. Serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels were detected by using liquidchromatography-tandem mass spectrometry (LC-MS/MS). The risk factors which might influence the severity of depression were screened by Logisticregression analysis. Results · The serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in the case group was lower than those in the controlgroup (P=0.012, P=0.000, P=0.000). The patients with moderate depression presented significantly lower serum 25 (OH) D3 and total 25 (OH) D2/D3 levelsthan the controls did (P=0.000), although no significant difference in serum 25 (OH) D2 levels was found between these two groups. As well, the serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in patients with severe depression were significantly lower than those in patients with moderate depression and controls (P<0.05). The body mass index of severe depression group was much higher than that of moderate depression group and control group (P=0.002). Both overweight/obesity and the concentration of vitamin D may be the major influencing factors of depression severity (P=0.034, P=0.011). Conclusion · Vitamin D2 and D3 deficiency in depressive patients, particularly in those patients with severe depression, was shown in the present study. In addition, overweight/obesity as well as the concentration of vitamin D may exert the significant influence on the severity of depression. Vitamin D supplementation and weight control may be needed to be considered in making therapeutic strategies of major depressive disorder.
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Objective·To compare the clinical features between different subtype bipolar patients with first mania episode, and to contribute to early identification of bipolar disorder. Methods·This study was based on the database named as National Bipolar Mania Pathway Survey (BIPAS). From November 2012 to January 2013, bipolar patients from 26 mental health facilities in China were enrolled in current study. The clinical features were compared between mania patients of different subtypes, including hypomania (groupⅠ), mania without psychotic symptoms (groupⅡ), mania with psychotic symptoms (group Ⅲ) and mixed state (group Ⅳ). Results·There was significant difference in the percentage of clinical symptoms between different subtype bipolar patients with first mania episode, especially the mania and anxiety related symptoms. Group Ⅰ, Ⅲ , Ⅳ were further compared with groupⅡ, which was considered as the typical bipolar disorder. The results showed that the mania related symptoms was significantly higher in group Ⅱ, but anxiety related symptoms was significantly higher in group Ⅰ, Ⅲ, Ⅳ. Moreover, Logistic regression analysis revealed that more eloquent or humor and unusually restless could be in favor of the diagnosis of hypomania; younger and mania or hypomania as first episode might be in favor of the diagnosis of mania with psychotic symptoms; older, national minorities and unusually restless could be in favor of the diagnosis of mixed state. Conclusion·The clinical features between different subtype bipolar patients with first mania episode are various, and analysis of the clinical features can contribute to early identification of bipolar disorder.
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Objective To analyze the risk factors of socio-demographic and clinical characteristics related to anxious symptoms in bipolar depression patients(BDP).Methods This was a secondary analysis of data from the Diagnostic Assessment Service for People with Bipolar Depression in China(DASP)from September 1,2010 to February 28,2011.According to the criterion that comorbid anxiety or not, BDP(n=306)were divided into comorbid anxiety group(n =200)(65.4％)and without anxiety group(n =106)(34.6％).Further analysis for risk factors of anxious symptoms in BDP was performed by the multivariate logistic regression analysis.Results BDP with anxiety were younger(35.10± 11.09), younger at illness onset(27.93-± 10.04), ruore male(t =4.603, P＜0.05), more lifetime episodes(3.21 ± 3.77), frequently episodes(t =17.328,P＜0.05),inducement onset(t=14.859,P＜0.05)and more seasonal episodes(t=8.300,P＜0.05)compared with BDP without anxiety.Logistic regression analysis showed that inducement onset(OR=5.023)and episodes frequency(OR=10.852)was significantly associated with anxious symptom(P＜0.05).Conclusion The finding indicates that postpartum onset and depressive episodes frequency may be risk factors of bipolar depression with anxiety.
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Objective To analyze the risk factors of socio-demographic and clinical characteristics related to anxious symptoms in bipolar depression patients(BDP).Methods This was a secondary analysis of data from the Diagnostic Assessment Service for People with Bipolar Depression in China(DASP)from September 1,2010 to February 28,2011.According to the criterion that comorbid anxiety or not, BDP(n=306)were divided into comorbid anxiety group(n =200)(65.4％)and without anxiety group(n =106)(34.6％).Further analysis for risk factors of anxious symptoms in BDP was performed by the multivariate logistic regression analysis.Results BDP with anxiety were younger(35.10± 11.09), younger at illness onset(27.93-± 10.04), ruore male(t =4.603, P＜0.05), more lifetime episodes(3.21 ± 3.77), frequently episodes(t =17.328,P＜0.05),inducement onset(t=14.859,P＜0.05)and more seasonal episodes(t=8.300,P＜0.05)compared with BDP without anxiety.Logistic regression analysis showed that inducement onset(OR=5.023)and episodes frequency(OR=10.852)was significantly associated with anxious symptom(P＜0.05).Conclusion The finding indicates that postpartum onset and depressive episodes frequency may be risk factors of bipolar depression with anxiety.
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Bipolar disorder (BD) is a chronic mental illness with high recurrence rate and disability. As one of the core symptoms, cognitive impairment may occurs at every stage of the disease. Evidence from the neuroimaging studies revealed that the abnormal brain volumes, the blood flow and oxygen saturation of key brain areas are related to executive impairment in patients with bipolar disorder. This article reviews current structural and functional neuroimaging studies about the executive impairment of patients with euthymic bipolar disorder and research progresses.
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Objective To explore the attempted suicide risk factors of socio-demographic and clinical charac-teristics in major depressive disorder patients with atypical features (e.g. increased appetite, weight gain and greater time spent sleeping). Methods This was a secondary analysis of the data from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and carried out in 13 major mental health centers in China. Totally 179 patients were diagnosed as atypical major depres-sive disorder patients in all 1172 major depressive disorder patients using Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-Ⅳ) by psychiatrists. Suicide attempters and nonattempters were grouped base on the interview results of suicidality module of the Mini International Neuro-psychiatric Interview (MINI). Multiple logistic regression were used to assess association between independent variables and attempted suicide in major depressive disorder patients with atypical features. Results The rater of attempted snicide was 23.5% (42/179) of atypical major depressive disorder patients reported prior or current attempted suicide. Compared to nonattempters, attempters had higher levels of suicidal ideation, postpartum depressive episodes, and the use of antipsychotic, mood stabilizers and benzodiazepines (P<0.05). Logistic regression analysis showed that number of admissions (OR=1.73, 95% CI: 1.093~2.740) and depressive episodes with suicidal ideation (OR=3.90, 95%CI: 1.506~10.092) were significantly associat-ed with attempted suicide in atypical unipolar depression patients (P<0.05). Conclusions High number of admissions and high levels of suicidal ideation may be considered as potential risk factors to identify atypical unipolar depression patients at risk for future suicidal behavior.
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Objective:To compare the suicidality risk in major depressive disorder (MDD)patients with and without anxious characteristics,and analyze the risk factors of suicidality in MDD patients. Methods:This was a secondary analysis of the data from the Diagnostic Assessment Service for people with Bipolar Disorders in China (DASP),which was initiated by the Chinese Society of Psychiatry (CSP),from September 1,2010 to February 28, 201 1. Based on the anxious module and suicide module of Mini International Neuropsychiatric Interview (M. I. N. I),1 172 MDD patients were classified as suffering from anxious MDD (n=728,62. 1%)and non-anxious MDD(n=444,37. 9%). Logistic regression was employed to examine the risk factors of suicidality in MDD pa-tients. Results:Among the anxious MDD patients,331 (45. 5%)of them had suicidality risk. And 54(12. 2%)of non-anxious MDD patients had suicidality risk. Compare to the non-anxious group,the anxious MDD patients had significantly higher suicidality risk (P<0. 00 1 ). Logistic regression analysis showed that more frequent depressive episodes (OR=2. 07 ),depressive episodes with psychotic symptoms (OR=2. 0 1 ),comorbid with anxious charac-teristics (OR=3. 18)or melancholic characteristics (OR=2. 90)were associated with suicidality risk in patients with MDD. Conclusion:It indicates that the anxious MDD patients may have higher suicidality risk than non-anx-ious MDD patients,and more frequent depressive episodes,depressive episodes with psychotic symptoms,comorbid with anxious characteristics or melancholic characteristics may be risk factors of suicidality in patients with MDD.
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Objective To analyze the risk factors of socio-demographic and clinical characteristics related to sui?cidal attempt in major depressive disorder (MDD) patients with anxious characteristics. Methods Based on the anxious module of Mini International Neuropsychiatric Interview (MINI), a total of 728 anxious MDD patients from 13 major men?tal health centers in China were classified as suicidal and non-suicidal attempt groups. Further analyses regarding risk factors of suicidal attempt in anxious MDD patients were performed by the multivariate logistic regression analysis. Re?sults Among the 728 patients with anxious MDD analyzed, 135 (18.5%) of them had suicidal attempt and 593 (81.5%) had non-suicidal attempt. Compared to the non-suicidal attempt group, patients with suicidal attempt had significantly earlier age onset[(32.3 ± 11.9) vs. (35.3 ± 13.1)], more lifetime depression episodes (median:2 vs. 2), more number of ad?missions (median: 1 vs. 0), more frequent depressive episodes (14.8% vs. 7.4%), more atypical characteristics (25.9%vs.15.0%), more suicidal ideation (78.5%vs. 50.3%) and more antidepressant use (81.5%vs. 71.2%). Logistic regression analysis showed that number of admissions (OR=1.18, 95%CI:1.02~1.37), frequent depressive episodes (OR=2.10, 95%CI:1.14~3.68), depressive episodes with suicidal ideation (OR=3.55, 95%CI:2.28~5.54) were associated with suicidal at?tempt in MDD patients with anxious characteristics (P<0.05). Conclusions More number of admissions, more frequent depressive episodes, comorbid suicidal ideation may be risk factors of suicidal attempt in anxious MDD patients.
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Objective To analyze the risk factors of socio-demographic and clinical characteristics related to sui?cide risk in misdiagnosed bipolar disorderⅡ(BPⅡ) treated for major depressive disorder. Methods A total of l478 con?secutive major depressive disorder patients were interviewed with the Mini International Neuropsychiatric Interview (MINI) in 13 major mental health centers in China. Of the 1478 patients, 190 patients were diagnosed BPⅡ, who were divided into two groups (nonsuicidal risk and suicidal risk) with the suicidality module of MINI. Logistic regression was performed to evaluate significant risk factors associated with suicide risk in misdiagnosed BPⅡtreated for major depres?sive disorder. Results Of the 190 patients, 116 were in the nonsuicidal risk group and 74 were in the suicidal risk group. In comparison to the nonsuicidal risk group, the suicidal risk group had younger age [(34.45 ± 11.18) vs.(37.23 ± 13.22), P=0.008], earlier age at onset [(26.20 ± 9.16) vs. (30.37 ± 11.59), P=0.007], and more suicidal ideation (82.4%vs. 53.4%, P=0.001). Logistic regression analysis showed that age (OR=0.969,95% CI:0.945~0.993) and depressive epi?sodes with suicidal ideation (OR=4.129,95%CI:2.030~8.397) were significantly associated with suicide risk in patients of misdiagnosed BPⅡtreated for major depressive disorder (P<0.05). Conclusions Younger age, severer suicidal ide?ation may be potential independent risk factors to suicide risk in BPⅡwith misdiagnosed with major depressive disor?der.
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Objective To compare the cost-effectiveness and cost-utility of venlafaxine and mirtazapine in patients with treatment-resistant major depression (TRD).Methods One hundred and five patients with TRD were enrolled in this study and grouped into venlafaxine treatment (n=50) and mirtazapine treatment (n=55) based on the double-blind randomization scheme generated by computer.The treatment costs of antidepressants during 8 weeks were calculated,the rates of clinical response and remission were taken as treatment effectiveness,and the quality-adjusted life years (QALYs) as treatment utility.The descriptive analysis and nonparametric test were used to compare the cost-effectiveness and cost-utility of different groups.Results During 8 weeks,the treatment cost of antidepressant was ￥ 1 396.44 for venlafaxine and ￥ 1 206.90 mirtazapine,and the difference between two groups was ￥ 189.54.The cost-effectiveness ratios between venlafaxine and mirtazapine were very close (differed ￥ 0.06 for remission rate and ￥ 1.08 for response rate respectively).There was no significant difference for cost-utility ratios between two groups (physical functioning Z=-0.15,P＞0.05 ; mental health Z=-0.54,P＞0.05).Conclusion Both cost-effectiveness and cost-utility of venlafaxine in patients with TRD are close between venlafaxine and mirtazapine.
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Objective To better understand the role of CREB signaling pathway in chronic mild stress (CMS), we investigated the alteration of CREB and p-CREB in CMS rats with and without fluoxetine hydrochloride. Methods Fifty adult male Sprague-Dawley rats were randomly divided into three groups:CMS group (26), fluoxtine group (12) and con-trol group (12). The rats in CMS group and fluoxtine group received 8 weeks of chronic mild stress. Rats in fluoxtine group were administered daily injections of fluoxetine 10mg/kg I.P. Sucrose preference tests and open-field test were car-ried out after the 8th week. Based on endpoint sucrose-intake, animals were further divided into 4 groups:CMS sensitive group, CMS resilient group, fluoxtine group and control group. Western blot was used to detect the expression levels of CREB and p-CREB in the hippocampus and prefrontal cortex. Results The sucrose consumption was significantly de-creased in CMS resilience group compared to sensitive group, control group and fluoxetine-intervention group (all P<0.05). Similarly, the numbers in total arm entries, percentage of entries into open arms and time spent in open arms was significantly lower in CMS resilience group compared to control group(all P<0.05), but not different compared to CMS sensitive group(all P<0.05). The p-CREB in the hippocampus was significantly lower in CMS sensitive rat compared to CMS resilience group, control group and fluoxetine-intervention group(all P<0.05), but CREB was not dfferent among the four groups(all P<0.05). Conclusions The elevated phosphorylation of CREB in the hippocampus and prefrontal cortex of resilience CMS rats may contribute to the mood alteration induced by stress.
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Objective To explore the role of default mode network (DMN) in the pathophysiology of depression and the correlations between the functional connectivity (FC) of DMN and the clinical characteristics of depression through the resting-state fMRI scan in depressed patients. Methods Sixteen medication-na?ve patients with major depressive disorder and 15 healthy controls were recruited and underwent the resting-state MRI scan. Hamiliton depression rating scale (HAMD) was used to evaluate patients’symptom. The FC of DMN and its correlations with clinical features of pa-tients were analyzed. Results Compared with healthy controls, the FC within DMN in depressed patients is disturbed. There were negative correlations between the left mPFC-left hippocampus FC and HAMD total scores (r=-0.569, P=0.021) and subscale scores for sluggishness (r=-0.498, P=0.050). The left mPFC-right hippocampus FC in patients was negatively correlated with HAMD scores (r=-0.508, P=0.045). There were negative correlations between FC in the hippo-campus and HAMD subscale scores for cognitive impairment (r=-0.509, P=0.044). Conclusions The results suggest that there is abnormal FC within DMN in drug-na?ve patients with depression during resting state and some abnormal altera-tions of FC may be correlated with the clinical characteristics in depression.
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Objective To evaluate the efficacy of antidepressants plus cognitive-behavioral education and self-management preventing the recurrent or deterioration of depression.Methods Outpatients with non-episode depression,Hamilton Rating Scales of Depression 17 items (HAMD17 ≥3),entered openly intervention group (n =30) and control group (n =30),and were followed up one year.Patients in intervention group received intervention,including treatment as usual,group education of cognitive behavior,self-help group attendance and self-management of depressive mood.Patients in control group only received treatment as usual.The primary outcome was time to recurrent or deterioration of depression.Kaplan-Meier methodology was used to evaluate differences of survival curves between two different groups.Results There were significant differences for risk of recurrent or deterioration (x2 =5.70,P ＜ 0.05) and one-year rate of recurrent or deterioration (intervention group 27％ (8/30),control group 53％ (16/30),x2 =4.44,P ＜ 0.05) between two groups,but not for average time of recurrent or deterioration (intervention group (4.75 ± 2.49) months,control group (6.63 ± 3.10) months,t =-1.48,P ＞0.05).There were no significant differences for risk of drop-out (x2 =1.66,P ＞ 0.05),one-year rate of drop-out (intervention group 13％ (4/30),control group 23％ (7/30),x2 =1.00,P ＞ 0.05) and average time of drop-out (intervention group (7.25 ± 3.78) months,control group (4.00 ± 2.58) months,t =1.71,P ＞ 0.05) between two groups.Conclusion Antidepressants plus cognitive-behavioral education and self-management can effectively prevent the recurrent or deterioration of depression.