Major depressive disorder(MDD)with suicidal ideation or behaviour(MDSI)is associated with an increased risk of future suicide.The timely identification of suicide risk in patients with MDD and the subsequent implement...Major depressive disorder(MDD)with suicidal ideation or behaviour(MDSI)is associated with an increased risk of future suicide.The timely identification of suicide risk in patients with MDD and the subsequent implementation of interventions are crucially important to reduce their suffering and save lives.However,the early diagnosis of MDSI remains challenging across the world,as no objective diagnostic method is currently available.In China,the challenge is greater due to the social stigma associated with mental health problems,leading many patients to avoid reporting their suicidal ideation.Additionally,the neural mechanisms underlying MDSl are stll unclear,which may hamper the development of effective interventions.We thus conducted this narrative review to summarise the existing neuroimaging studies of MDSI in Chinese patients,including those involving structural magnetic resonance imaging(MRI),functional MRl,neuronal electrophysiological source imaging of the brain dynamics with electroencephalography and magnetoencephalography.By synthesising the current research efforts in neuroimaging studies of Chinese patients with MDSl,we identified potential objective neuroimaging biomarkers,which may aid in the early identification of patients with MDSI who are at high suicide-related risk.Our findings also offer insights into the complex neural mechanisms underlying MDSI and suggest promising therapeutic targets.Furthermore,we propose future directions to discover novel imaging signatures,improve patient care,as well as help psychiatrists and clinical investigators plan their future research.展开更多
To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoami...To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.展开更多
Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disord...Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.展开更多
There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidenc...There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidence to support anhedonia as a core feature of MDD.In the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic features.Anhedonia is a multifaceted symptom that includes deficits in various aspects of reward processing,such as anticipatory anhedonia,consummatory anhedonia,and decision-making anhedonia.Anhedonia is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision making.However,the precise neurobiological mechanisms of anhedonia in MDD are not clearly understood.In this paper,we reviewed(1)the current understanding of the link between anhedonia and MDD;(2)the biological basis of the pathological mechanism of anhedonia in MDD;and(3)challenges in research on the pathological mechanisms of anhedonia in MDD.A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis,prediction,and treatment of patients with MDD in the future.展开更多
Background The association between inflammation and major depressive disorder(MDD)remains poorly understood,given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers,such as interleukin(IL...Background The association between inflammation and major depressive disorder(MDD)remains poorly understood,given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers,such as interleukin(IL)-6,high-sensitivity C reactive protein(hsCRP)and tumour necrosis factor-α.(TNF-α)in melancholic,atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.Methods The sample consisted of participants(aged 18-55 years)from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov,including melancholic(n=44),atypical(n=37)and anxious(n=44)patients with depression and healthy controls(HCs)(n=33).Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology,Self-Rated Version and the.17-item Hamilton Depression Rating Scale.Blood levels.of TNF-α,IL-6 and hsCRP were assessed using antibody array analysis.Results Patients with MDD,classified according to melancholic,atypical and anxious depression subtypes,and HCs did not differ significantly in baseline TNF-α,IL-6 and hsCRP levels after adjustment.In patients with anxious depression,hsCRP levels increased significantly if they experienced no pain(adjusted(adj.)p=0.010)or mild to moderate pain(adj.p=0.038)compared with those with severe pain.However,the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain(p=0.022;adj.p=0.155).Baseline TNF-α(adj.p=0.038)and IL-6(adj.p=0.006)levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.Conclusions This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic,atypical and anxious depression subtypes.Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.展开更多
Background： Patients with major depressive disorder （MDD） usually have high risk of suicidality. Few studies have investigated the effects of stressful life events （SLEs） on the risk of suicide in Chinese patient...Background： Patients with major depressive disorder （MDD） usually have high risk of suicidality. Few studies have investigated the effects of stressful life events （SLEs） on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. Methods： In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview （MINI） criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Harnilton Depression Scale （HAMD-17）. The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. Results： No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness （HPS） and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs （odds ratio [OR] = 1.54, 95% confidence interval [C1]： 1.16-2.05, P = 0.003） and depressive symptoms （OR = 1.08.95% CI： 1.05-1.11, P 〈 0.001 ） were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. Conclusions： HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. Trial Registration： ClinicalTrials.gov： NCT02023567; https：//clinicaltrials.gov/ct2/show/NCTO2023567？term=NCTO2023567＆rank=l.展开更多
Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment a...Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns ofantipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life （QOL）. Methods： A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients＇ socio-demographic and clinical characteristics including psychopathology, medication side effects. satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. Results： The frequency ofantipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively （χ^2 = 90.3, df= 2, P 〈 0.001 ）. Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals （i.e., Level-Ⅲ hospital）. Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. Conclusions： Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients＇ and relatives＇ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.展开更多
Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence....Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence.This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.Methods:In total,547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included.These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders,4th Edition criteria.Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS).Quality of life was assessed by a 36-item Short-form Health Survey (SF-36).Analyses were performed using a continuous or dichotomous (cut-off:30 years)age-of-onset indicator.Results:Early-onset MDD (EOD,＜30 years) was associated with longer illness (P =0.003),unmarried status (P ＜ 0.001),higher neuroticism (P ≤ 0.002) based on the SCL-90-R,and more limited social function and mental health (P =0.006,P =0.007) based on the SF-36 and SDS.The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages.Special clinical features and more impaired social function and quality of life were associated with EOD,as in western studies.Conclusions:EOD often follows higher levels of neuroticism.Age of onset of MDD may be a predictor of clinical features and impaired social function,allowing earlier diagnosis and treatment.展开更多
Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying...Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.展开更多
Major depressive disorder(MDD)is a prevalent,often chronic,and highly disabling multidimensional psychiatric illness.[1] Moreover,co-occurring anxiety symptoms are extremely common among patients with MDD;up to 90%of ...Major depressive disorder(MDD)is a prevalent,often chronic,and highly disabling multidimensional psychiatric illness.[1] Moreover,co-occurring anxiety symptoms are extremely common among patients with MDD;up to 90%of patients present with anxiety symptoms.[2]Notably,high levels of anxiety symptoms may predict worse clinical outcomes because of poor response to pharmacotherapy for MDD.[3]So use of augmentation or combination strategies during early course of treatment could be necessary,but ensuring the accurate and timely change is difficult because of the lack of consensus to assess the early improvement of initial treatment.To date,replicated evidence indicates that the lack of early improvement(eg,<20% reduction in a depression scale score)in 2 weeks can be an accurate predictor to identify eventual non?responders?4*This study aimed to evaluate the early onset of antidepressant action and clinical outcomes in patients with MDD and high anxiety,and to explore the potential influencing factors of early onset improvement.展开更多
Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chron...Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.Methods:Sixty-four adolescent,male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,n =32) or normal housing conditions (control group,n =32).At 15 months of age,16 mice were randomly selected from each group for a series of behavioral tests,including two depression-related tasks (the sucrose preference test and the tail suspension test).Three days following the last behavioral test,eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)-and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons,and the expression levels of vesicular transporters of glutamate-1 (VGIuT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC],hippocampus,and amygdala).Results:Behaviorally,compared with the control group,adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs.43.11 ± 2.85%,t(22)=3.417,P =0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs.33.14 ± 5.95 s,t(25)=2.394,P =0.025),but did not affect anxiety-like behaviors and pre-pulse inhibition.At the neurobiologic level,adolescent stress down-regulated PV+,not CR+,inter-neuron density in the mPFC (F(1,39)=19.30,P < 0.001),and hippocampus (F(1,42)=5.823,P =0.020) and altered the CR+,not PV+,inter-neuron density in the amygdala (F(1,28)=23.16,P < 0.001).The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09,all P < 0.004),which suggests stress-induced hypoexcitability in these regions.Conclusions:Chronic stress during adolescence increased depression-like behaviors in aged mice,which may be associated with the F/I imbalance in stress-sensitive brain regions.展开更多
Background:Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations.One deleterious effect of ear...Background:Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations.One deleterious effect of early-life stress that manifests in later life is sleep disturbance,but this has not been examined in aged mice and the underlying neural mechanisms remain unknown.Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation,this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.Methods:Twenty aged male C57BL/6 mice (>16 months,n =10 per group) were used in this study.During post-natal days 2 to 9,dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed).When the mice were 16 to 17 months old,their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram.The amount of each sleep-wake stage,mean duration,and stage transition was analyzed.Then,five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry.Group comparisons were carried out using Student t test or analysis of variances when appropriate.Results:Compared with the control mice,the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs.631.33 ± 34.73 min,t17 =2.376,P =0.030),accordingly,non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs.723.54 ± 39.21 min,t17 =2.326,P =0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs.89.39 ± 12.69 min,t17 =3.277,P =0.004).Meanwhile,we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1,16) =81.04,P < 0.001).Conclusion:Early adverse experiences disrupt sleep behaviors in aged mice,which might be associated with the excitatory-inhibitory imbalance in the NAc.展开更多
Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood,one of which is sleep disturbance.As the corticotropin-releasing hormone(CRH)–corticotropin-releasing hormon...Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood,one of which is sleep disturbance.As the corticotropin-releasing hormone(CRH)–corticotropin-releasing hormone receptor 1(CRHR1)system and nucleus accumbens(NAc)play important roles in both stress responses and sleep-wake regulation,in this study we investigated whether the NAc CRH–CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice.Using the limited nesting and bedding material paradigm from postnatal days 2 to 9,we found that early-life stress disrupted sleep-wake behaviors during adulthood,including increased wakefulness and decreased non-rapid eye movement(NREM)sleep time during the dark period and increased rapid eye movement(REM)sleep time during the light period.The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure.Importantly,Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology,whereas NAc Crhr1 knockdown reversed these effects(including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy).Together,our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc,and highlight the critical role of the NAc CRH–CRHR1 system in modulating these negative outcomes evoked by early-life stress.展开更多
文摘Major depressive disorder(MDD)with suicidal ideation or behaviour(MDSI)is associated with an increased risk of future suicide.The timely identification of suicide risk in patients with MDD and the subsequent implementation of interventions are crucially important to reduce their suffering and save lives.However,the early diagnosis of MDSI remains challenging across the world,as no objective diagnostic method is currently available.In China,the challenge is greater due to the social stigma associated with mental health problems,leading many patients to avoid reporting their suicidal ideation.Additionally,the neural mechanisms underlying MDSl are stll unclear,which may hamper the development of effective interventions.We thus conducted this narrative review to summarise the existing neuroimaging studies of MDSI in Chinese patients,including those involving structural magnetic resonance imaging(MRI),functional MRl,neuronal electrophysiological source imaging of the brain dynamics with electroencephalography and magnetoencephalography.By synthesising the current research efforts in neuroimaging studies of Chinese patients with MDSl,we identified potential objective neuroimaging biomarkers,which may aid in the early identification of patients with MDSI who are at high suicide-related risk.Our findings also offer insights into the complex neural mechanisms underlying MDSI and suggest promising therapeutic targets.Furthermore,we propose future directions to discover novel imaging signatures,improve patient care,as well as help psychiatrists and clinical investigators plan their future research.
文摘To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.
基金the National Key Technology R&D Program(2015BA/13B01)Beijing National Science Foundation(7222236)+1 种基金Capital Health Research and Development of Special Fund(2022-1-4111)National Natural Science Foundation of China(82071528,82171529,82271569,82371530).
文摘Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.
基金This study was supported by the National Natural Science Foundation of China(No.81630031)National Key Technology R&D Program(2015BAI13B01).
文摘There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidence to support anhedonia as a core feature of MDD.In the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic features.Anhedonia is a multifaceted symptom that includes deficits in various aspects of reward processing,such as anticipatory anhedonia,consummatory anhedonia,and decision-making anhedonia.Anhedonia is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision making.However,the precise neurobiological mechanisms of anhedonia in MDD are not clearly understood.In this paper,we reviewed(1)the current understanding of the link between anhedonia and MDD;(2)the biological basis of the pathological mechanism of anhedonia in MDD;and(3)challenges in research on the pathological mechanisms of anhedonia in MDD.A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis,prediction,and treatment of patients with MDD in the future.
基金Key Projects of Clinical Research Center of Shanghai Mental Health Center(grant number CRC2018ZD02)key supporting projects of Clinical Research Center of Shanghai Mental Health Center(grant number SHDC 2020CR6023)+2 种基金Research and DevelopmentProgramof China(grant number 2016YFC1307100)Shanghai Key Project of Science and Technology(grant number 2018SHZDZX05)Natural Science Foundation of China(grant number 81771465,81801338 and 81930033).
文摘Background The association between inflammation and major depressive disorder(MDD)remains poorly understood,given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers,such as interleukin(IL)-6,high-sensitivity C reactive protein(hsCRP)and tumour necrosis factor-α.(TNF-α)in melancholic,atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.Methods The sample consisted of participants(aged 18-55 years)from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov,including melancholic(n=44),atypical(n=37)and anxious(n=44)patients with depression and healthy controls(HCs)(n=33).Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology,Self-Rated Version and the.17-item Hamilton Depression Rating Scale.Blood levels.of TNF-α,IL-6 and hsCRP were assessed using antibody array analysis.Results Patients with MDD,classified according to melancholic,atypical and anxious depression subtypes,and HCs did not differ significantly in baseline TNF-α,IL-6 and hsCRP levels after adjustment.In patients with anxious depression,hsCRP levels increased significantly if they experienced no pain(adjusted(adj.)p=0.010)or mild to moderate pain(adj.p=0.038)compared with those with severe pain.However,the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain(p=0.022;adj.p=0.155).Baseline TNF-α(adj.p=0.038)and IL-6(adj.p=0.006)levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.Conclusions This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic,atypical and anxious depression subtypes.Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.
文摘Background： Patients with major depressive disorder （MDD） usually have high risk of suicidality. Few studies have investigated the effects of stressful life events （SLEs） on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. Methods： In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview （MINI） criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Harnilton Depression Scale （HAMD-17）. The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. Results： No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness （HPS） and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs （odds ratio [OR] = 1.54, 95% confidence interval [C1]： 1.16-2.05, P = 0.003） and depressive symptoms （OR = 1.08.95% CI： 1.05-1.11, P 〈 0.001 ） were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. Conclusions： HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. Trial Registration： ClinicalTrials.gov： NCT02023567; https：//clinicaltrials.gov/ct2/show/NCTO2023567？term=NCTO2023567＆rank=l.
文摘Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns ofantipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life （QOL）. Methods： A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients＇ socio-demographic and clinical characteristics including psychopathology, medication side effects. satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. Results： The frequency ofantipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively （χ^2 = 90.3, df= 2, P 〈 0.001 ）. Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals （i.e., Level-Ⅲ hospital）. Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. Conclusions： Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients＇ and relatives＇ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.
文摘Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence.This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.Methods:In total,547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included.These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders,4th Edition criteria.Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS).Quality of life was assessed by a 36-item Short-form Health Survey (SF-36).Analyses were performed using a continuous or dichotomous (cut-off:30 years)age-of-onset indicator.Results:Early-onset MDD (EOD,＜30 years) was associated with longer illness (P =0.003),unmarried status (P ＜ 0.001),higher neuroticism (P ≤ 0.002) based on the SCL-90-R,and more limited social function and mental health (P =0.006,P =0.007) based on the SF-36 and SDS.The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages.Special clinical features and more impaired social function and quality of life were associated with EOD,as in western studies.Conclusions:EOD often follows higher levels of neuroticism.Age of onset of MDD may be a predictor of clinical features and impaired social function,allowing earlier diagnosis and treatment.
基金supported by the National Natural Science Foundation of China(81401129,81571321,81630031,and 81571312)the Peking University Medicine Seed Fund for Interdisciplinary Research (BMU2017MX021)+1 种基金the National Key Basic Research Program of China (2015CB856401)the Beijing Brain Project (Z171100000117016)。
文摘Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
基金This study was sponsored by Sumitomo Dainippon Pharma Co.,Ltd.(Suzhou,China.No.SPC-SED1102)The analysis and writing were partially supported by the National Key Technology R&D Program(No.2015BAI13B01)The funders had no role in the study design,collection analysis,conduct of the study or in the writing and preparation of the manuscript or the decision to publish.
文摘Major depressive disorder(MDD)is a prevalent,often chronic,and highly disabling multidimensional psychiatric illness.[1] Moreover,co-occurring anxiety symptoms are extremely common among patients with MDD;up to 90%of patients present with anxiety symptoms.[2]Notably,high levels of anxiety symptoms may predict worse clinical outcomes because of poor response to pharmacotherapy for MDD.[3]So use of augmentation or combination strategies during early course of treatment could be necessary,but ensuring the accurate and timely change is difficult because of the lack of consensus to assess the early improvement of initial treatment.To date,replicated evidence indicates that the lack of early improvement(eg,<20% reduction in a depression scale score)in 2 weeks can be an accurate predictor to identify eventual non?responders?4*This study aimed to evaluate the early onset of antidepressant action and clinical outcomes in patients with MDD and high anxiety,and to explore the potential influencing factors of early onset improvement.
基金grants from the National Natural Science Foundation of China (Nos. 81630031, 81401129, 81571321, and 81571312)the Beijing Brain Project (No.Z171100000117016), the National Key Basic Research Program of China (973 program+1 种基金No. 2015CB856401)the Peking University Medicine Seed Fund for Interdisciplinary Research (No. BMU2017MX021).
文摘Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.Methods:Sixty-four adolescent,male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,n =32) or normal housing conditions (control group,n =32).At 15 months of age,16 mice were randomly selected from each group for a series of behavioral tests,including two depression-related tasks (the sucrose preference test and the tail suspension test).Three days following the last behavioral test,eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)-and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons,and the expression levels of vesicular transporters of glutamate-1 (VGIuT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC],hippocampus,and amygdala).Results:Behaviorally,compared with the control group,adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs.43.11 ± 2.85%,t(22)=3.417,P =0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs.33.14 ± 5.95 s,t(25)=2.394,P =0.025),but did not affect anxiety-like behaviors and pre-pulse inhibition.At the neurobiologic level,adolescent stress down-regulated PV+,not CR+,inter-neuron density in the mPFC (F(1,39)=19.30,P < 0.001),and hippocampus (F(1,42)=5.823,P =0.020) and altered the CR+,not PV+,inter-neuron density in the amygdala (F(1,28)=23.16,P < 0.001).The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09,all P < 0.004),which suggests stress-induced hypoexcitability in these regions.Conclusions:Chronic stress during adolescence increased depression-like behaviors in aged mice,which may be associated with the F/I imbalance in stress-sensitive brain regions.
基金grants from the National Key Basic Research Program of China(973 program,No.2015CB856401)the National Natural Science Foundation of China(Nos.81630031,81571321,and 81571312)+1 种基金the Peking University Medicine Seed Fund for Interdisciplinary Research(No.BMU2017MX021)the Beijing Brain Project(No.Z171100000117016).
文摘Background:Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations.One deleterious effect of early-life stress that manifests in later life is sleep disturbance,but this has not been examined in aged mice and the underlying neural mechanisms remain unknown.Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation,this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.Methods:Twenty aged male C57BL/6 mice (>16 months,n =10 per group) were used in this study.During post-natal days 2 to 9,dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed).When the mice were 16 to 17 months old,their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram.The amount of each sleep-wake stage,mean duration,and stage transition was analyzed.Then,five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry.Group comparisons were carried out using Student t test or analysis of variances when appropriate.Results:Compared with the control mice,the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs.631.33 ± 34.73 min,t17 =2.376,P =0.030),accordingly,non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs.723.54 ± 39.21 min,t17 =2.326,P =0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs.89.39 ± 12.69 min,t17 =3.277,P =0.004).Meanwhile,we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1,16) =81.04,P < 0.001).Conclusion:Early adverse experiences disrupt sleep behaviors in aged mice,which might be associated with the excitatory-inhibitory imbalance in the NAc.
基金supported by the National Key Basic Research Program of China(973 Program,2015CB856401)the Beijing National Science Foundation(7222236)+1 种基金the Capital Medical Development Research Fund(2020-2-4113)the National Natural Science Foundation of China(81630031,81771468,82071528,and 82171529).
文摘Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood,one of which is sleep disturbance.As the corticotropin-releasing hormone(CRH)–corticotropin-releasing hormone receptor 1(CRHR1)system and nucleus accumbens(NAc)play important roles in both stress responses and sleep-wake regulation,in this study we investigated whether the NAc CRH–CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice.Using the limited nesting and bedding material paradigm from postnatal days 2 to 9,we found that early-life stress disrupted sleep-wake behaviors during adulthood,including increased wakefulness and decreased non-rapid eye movement(NREM)sleep time during the dark period and increased rapid eye movement(REM)sleep time during the light period.The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure.Importantly,Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology,whereas NAc Crhr1 knockdown reversed these effects(including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy).Together,our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc,and highlight the critical role of the NAc CRH–CRHR1 system in modulating these negative outcomes evoked by early-life stress.
