Major depressive disorder (MDD) is a common mental illness with high lifetime prevalence close to 20%. Positron emission tomography (PET) studies have reported decreased prefrontal, insular and limbic cerebral glucose metabolism in depressed patients compared with healthy controls. However, the literature has not always been consistent. To evaluate current evidence from PET studies, we conducted a voxel-based meta-analysis of cerebral metabolism in MDD.
Data were collected from databases including PubMed and Web of Science, with the last report up to April 2013. Voxel-based meta-analyses were performed using the revised activation likelihood estimation (ALE) software.
Ten whole-brain-based FDG-PET studies in MDD were included in the meta-analysis, comprising 188 MDD patients and 169 healthy controls. ALE analyses showed the brain metabolism in bilateral insula, left lentiform nucleus putamen and extra-nuclear, right caudate and cingulate gyrus were significantly decreased. However, the brain activity in right thalamus pulvinar and declive of posterior lobe, left culmen of vermis in anterior lobe were significantly increased in MDD patients.
Our meta-analysis demonstrates the specific brain regions where possible dysfunctions are more consistently reported in MDD patients. Altered metabolism in insula, limbic system, basal ganglia, thalamus, and cerebellum and thus these regions are likely to play a key role in the pathophysiology of depression.
Major depressive disorder; Positron emission tomography; Meta-analysis; Activation likelihood estimation
To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers.
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.
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.
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.
The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years.
We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders.
In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.
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?
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.
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.
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.
Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia.
We examined the clinical features in 5,950 Han Chinese women with MDD between 30–60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two data sets. We identified sixteen stressful life events that significantly increase the risk of dysthymia, given the presence of MDD. Low parental warmth, from either mother or father, increases the risk of dysthymia. Highly threatening but short-lived threats (such as rape) are more specific for MDD than dysthymia. While for MDD more severe life events show the largest odds ratio versus controls, this was not seen for cases of MDD with or without dysthymia.
There are increased rates of stressful life events in MDD with dysthymia, but the impact of life events on susceptibility to dysthymia with MDD differs from that seen for MDD alone. The pattern does not fit a simple dose-response relationship, suggesting that there are moderating factors involved in the relationship between environmental precipitants and the onset of dysthymia. It is possible that severe life events in childhood events index a general susceptibility to chronic depression, rather than acting specifically as risk factors for dysthymia.
The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.
Cognitive theorists relate anxiety disorders to the way in which emotional information is processed. The existing research suggests that patients with anxiety disorders tend to allocate their attention toward threat-related information selectively, and this may differ among different types of anxious subjects. The aim of this study was to explore attentional bias in patients with generalized anxiety disorder (GAD) and panic disorder (PD) using the emotional Stroop task and compare the differences between them.
Forty-two patients with GAD, 34 patients with PD, and 46 healthy controls performed the emotional Stroop task with four word types, ie, GAD-related words, PD-related words, neutral words, and positive words.
Patients with GAD and those with PD were slower than healthy controls to respond to all stimuli. Patients with GAD had longer response latencies in color-naming both PD-relevant words and GAD relevant words. Patients with PD had longer response latencies only in color-naming PD-related words, similar to healthy controls.
Patients with GAD and those with PD had a different pattern of attentional bias, and there was insufficient evidence to support the existence of specific attentional bias in patients with PD.
generalized anxiety disorder; panic disorder; attentional bias; emotional Stroop task
This review summarizes the first clinical reports from the CONVERGE consortium: China, Oxford and VCU Experimental Research on Genetic Epidemiology. CONVERGE sets out to investigate the nature and mode of action of the genetic and environmental risk factors for major depressive disorder (MDD). CONVERGE aims to collect 6000 cases of recurrent MDD and 6000 controls. The consortium includes hospitals in 30 cities, all with populations exceeding 5 million, and has collected over 2000 cases and controls. High quality phenotype data on MDD collected in China is now available to determine the source and nature of this highly heterogeneous condition. Analyses reported in a series of papers indicate that the clinical features and risk factors of MDD are sufficiently similar to those in the West that we can confidently predict that the results of subsequent analyses will be widely applicable.
Major depressive disorder; China; Co-morbidity; Anxiety
Studies using event-related potential (ERP) methods have reported a relationship between the cognitive dysfunction of patients with schizophrenia and P300 latency and amplitude, but it remains uncertain whether or not these indices change as cognitive functioning improves with pharmacological treatment.
Pool the results from follow-up studies conducted in China to determine the relationship of treatment with antipsychotic medication to changes in P300 indices.
Studies conducted in China and published in English or Chinese from January 1982 to December 2011 that reported P300 latency and amplitude in patients with schizophrenia before and after treatment with antipsychotic medications were identified by electronic and hand searches, and the 12 studies that met inclusion criteria for the meta-analysis were independently reviewed by two evaluators. The peak P300 amplitude results for the 17 samples reported in the 12 studies were homogenous so a fixed-effects model was used to assess pooled standardized effect size (PSES); but the results for P300 latency were heterogeneous so a random-effects model was used to compute PSES. Publication bias was assessed using Egger's test, Begg's test and funnel plots.
Of the pooled sample of 611 participants, the 502 participants (82.2%) who completed P300 latency and amplitude measures both before and after treatment were included in the meta-analysis. We found that antipsychotic treatment is associated with a small but significant increase in the amplitude of P300 (PSES=0.39, 95% CI [0.26, 0.51], z=6.14, p<0.001) and a small but significant decrease in the latency of P300 (PSES= -0.29, 95% CI [-0.51, -0.07]; z=2.58; p=0.010). There was no significant publication bias in either of the results.
In contrast to meta-analysis from western countries — that are primarily based on cross-sectional studies — the current meta-analysis of follow-up treatment studies of schizophrenia in China found that P300 amplitude and latency both change with pharmacological treatment. These findings suggest that P300 indices, particularly P300 amplitude, could be valuable biomarkers to monitor changes in cognitive functioning during treatment of patients with schizophrenia.
Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting.
Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD.
Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide.
Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample.
The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.
Major depressive disorder; Education; Socio-economic status; Symptom
Post partum depression (PPD) is relatively common in China but its clinical characteristics and risk factors have not been studied. We set out to investigate whether known risk factors for PPD could be found in Chinese women.
A case control design was used to determine the impact of known risk factors for PPD in a cohort of 1970 Chinese women with recurrent DSM-IV major depressive disorder (MDD). In a within-case design we examined the risk factors for PPD in patients with recurrent MDD. We compared the clinical features of MDD in cases with PPD to those without MDD. Odds ratios were calculated using logistic and ordinal regression.
Lower occupational and educational statuses increased the risk of PPD, as did a history of pre-menstrual symptoms, stressful life events and elevated levels of the personality trait of neuroticism. Patients with PPD and MDD were more likely to experience a comorbid anxiety disorder, had a younger age of onset of MDD, have higher levels of neuroticism and dysthymia.
Results obtained in this clinical sample may not be applicable to PPD within the community. Data were obtained retrospectively and we do not know whether the correlations we observe have the same causes as those operating in other populations.
Our results are consistent with the hypothesis that the despite cultural differences between Chinese and Western women, the phenomenology and risk factors for PPD are very similar.
Postpartum depression; Major depressive disorder; Neuroticism; Anxiety disorder
Diagnostic information for psychiatric research often depends on both clinical interviews and medical records. Although discrepancies between these two sources are well known, there have been few studies into the degree and origins of inconsistencies.
We compared data from structured interviews and medical records on 1,970 Han Chinese women with recurrent DSM-IV major depression (MD). Correlations were high for age at onset of MD (0.93) and number of episodes (0.70), intermediate for family history (+0.62) and duration of longest episode (+0.43) and variable but generally more modest for individual depressive symptoms (mean kappa = 0.32). Four factors were identified for twelve symptoms from medical records and the same four factors emerged from analysis of structured interviews. Factor congruencies were high but the correlation of factors between interviews and records were modest (i.e. +0.2 to +0.4).
Structured interviews and medical records are highly concordant for age of onset, and the number and length of episodes, but agree more modestly for individual symptoms and symptom factors. The modesty of these correlations probably arises from multiple factors including i) inconsistency in the definition of the worst episode, ii) inaccuracies in self-report and iii) difficulties in coding medical records where symptoms were recorded solely for clinical purposes.
The personality trait of neuroticism is a risk factor for major depressive disorder (MDD), but this relationship has not been demonstrated in clinical samples from Asia.
We examined a large-scale clinical study of Chinese Han women with recurrent major depression and community-acquired controls.
Elevated levels of neuroticism increased the risk for lifetime MDD (with an odds ratio of 1.37 per SD), contributed to the comorbidity of MDD with anxiety disorders, and predicted the onset and severity of MDD. Our findings largely replicate those obtained in clinical populations in Europe and US but differ in two ways: we did not find a relationship between melancholia and neuroticism; we found lower mean scores for neuroticism (3.6 in our community control sample).
Our findings do not apply to MDD in community-acquired samples and may be limited to Han Chinese women. It is not possible to determine whether the association between neuroticism and MDD reflects a causal relationship.
Neuroticism acts as a risk factor for MDD in Chinese women, as it does in the West and may particularly predispose to comorbidity with anxiety disorders. Cultural factors may have an important effect on its measurement.
Major depressive disorder; Anxiety disorders; Neuroticism
The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD.
We examined the clinical features in 1970 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 dysthymia and between dysthymia and disorders comorbid with major depression.
The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events.
Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships.
The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD.
Major depressive disorder; Dysthymia; Symptom; Comorbidity
Individuals with early-onset depression may be a clinically distinct group with particular symptom patterns, illness course, comorbidity and family history. This question has not been previously investigated in a Han Chinese population.
We examined the clinical features of 1970 Han Chinese women with DSM-IV major depressive disorder (MDD) between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models was used to determine the association between age at onset (AAO) with continuous, binary and discrete characteristic clinical features of MDD.
Earlier AAO was associated with more suicidal ideation and attempts and higher neuroticism, but fewer sleep, appetite and weight changes. Patients with an earlier AAO were more likely to suffer a chronic course (longer illness duration, more MDD episodes and longer index episode), increased rates of MDD in their parents and a lower likelihood of marriage. They tend to have higher comorbidity with anxiety disorders (general anxiety disorder, social phobia and agoraphobia) and dysthymia.
Early AAO in MDD may be an index of a more severe, highly comorbid and familial disorder. Our findings indicate that the features of MDD in China are similar to those reported elsewhere in the world.
Major depressive disorder; Age at onset; Symptom; Comorbidity
In European and US studies, patients with major depressive disorder (MDD) report more stressful life events (SLEs) than controls, but this relationship has rarely been studied in Chinese populations.
Sixteen lifetime SLEs were assessed at interview in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MDD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.
60% of controls and 72% of cases reported at least one lifetime SLE. Fourteen of the sixteen SLEs occurred significantly more frequently in those with MDD (median odds ratio of 1.6). The three SLEs most strongly associated with risk for MDD (OR > 3.0) preceded the onset of MDD the majority of the time: rape (82%), physical abuse (100%) and serious neglect (99%).
Our results may apply to females only. SLEs were rated retrospectively and are subject to biases in recollection. We did not assess contextual information for each life event.
More severe SLEs are more strongly associated with MDD. These results support the involvement of psychosocial adversity in the etiology of MDD in China.
Major depressive disorder; Stressful life event; Social adversity; Symptom
Anxiety disorders are highly prevalent internationally, and constitute a substantial social and economic burden for patients, their families, and society. A number of neuroimaging studies have investigated the etiology of anxiety disorders in China in the last decade. We discuss the findings of these studies, and compare them with the results of neuroimaging studies of anxiety disorders outside China.
A literature search was conducted using the Chinese BioMedical Literature Database, the Chinese Scientific and Technical Periodicals Database, the Chinese Journal Full-text Database, and PubMed, from 1989 to April 2009. We selected neuroimaging studies in which all participants and researchers were Chinese.
Twenty-five studies fit our inclusion criteria. Nine studies examined general anxiety disorder (GAD) and/or panic disorder (PD), eight examined obsessive-compulsive disorder (OCD), and eight examined posttraumatic stress disorder (PTSD). Our literature review revealed several general findings. First, reduced regional cerebral blood flow (rCBF) was found in the frontal lobe and temporal lobe in patients with GAD and PD compared with healthy controls. Second, when viewing images with negative and positive valence, relatively increased or decreased activation was found in several brain areas in patients with GAD and PD, respectively. Third, studies with positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) imaging revealed that OCD patients exhibited hyperperfusion and hypoperfusion in some brain regions compared with healthy controls. Neuroimaging studies of PTSD indicate that the hippocampal volume and the N-acetylaspartic acid (NAA) level and the NAA/creatine ratio in the hippocampus are decreased in patients relative to controls.
Neuroimaging studies within and outside China have provided evidence of specific neurobiological changes associated with anxiety disorders. However, results have not been entirely consistent across different studies of patients with the same diagnoses. International collaborative research using large samples and robust designs should be conducted in future.
anxiety disorders; neuroimaging; GAD; PD; OCD; PTSD
Studies of mental disorders using single photon emission computed tomography (SPECT) have been done for many years in China. Many results have been obtained. We review these findings and introduce them to the outside world.
SPECT papers available on the Chinese Biomedical Bibliographic Database, focusing on depression, schizophrenia, Alzheimer’s disease (AD), vascular dementia (VD), anxiety disorder, and obsessive compulsive disorder (OCD) in China, were reviewed and the results were compared with those obtained outside China.
We found that regional cerebral blood flow (rCBF) was abnormal in mental disorders, but the specificity of the abnormality is not yet consistent. Lower perfusion of rCBF could be seen in frontal, temporal, and parietal lobes of patients with depression, AD, schizophrenia, and VD. It seems that abnormality of the frontal lobe is more common in depression and schizophrenia, but temporal lobe abnormalities are more common in AD and VD. The perfusion of rCBF in the parietal lobe seems to be related to aging. Abnormalities in the occipital lobe and basal ganglia seem to be more associated with vascular problems. Thalamic dysfunction was mainly correlated with VD, and that of the cingulate largely with depression and schizophrenia. Hippocampal abnormalities were associated with AD. There were few reports on changes in anxiety disorders and other mental problems.
There is no specific biological marker of SPECT for individual mental disorders. Further study is needed to provide more specific information on the pathophysiology of mental disorders. It seems that brain abnormalities are similar in Chinese and non Chinese psychiatric patients.
depression; Alzheimer’s disease; vascular dementia; schizophrenia; anxiety disorder; obsessive compulsive disorder; SPECT
A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD.
We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30–60 years of age. Odds Ratios were calculated by logistic regression.
Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous.
The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states. Depression and Anxiety 0:1–6, 2011. © 2011 Wiley-Liss, Inc.
major depression; family history; symptom; life events
Although the diagnosis of melancholia has had a long history, the validity of the current DSM-IV definition remains contentious. We report here the first detailed comparison of melancholic and nonmelancholic major depression (MD) in a Chinese population examining in particular whether these two forms of MD differ quantitatively or qualitatively.
DSM-IV criteria for melancholia were applied to 1,970 Han Chinese women with recurrent MD recruited from 53 provincial mental health centers and psychiatric departments of general medical hospitals in 41 cities. Statistical analyses, utilizing Student's t-tests and Pearson's χ2, were calculated using SPSS 13.0.
Melancholic patients with MD were distinguished from nonmelancholic by being older, having a later age at onset, more episodes of illness and meeting more A criteria. They also had higher levels of neuroticism and rates of lifetime generalized anxiety disorder, panic disorder, and social and agoraphobia. They had significantly lower rates of childhood sexual abuse but did not differ on other stressful life events or rates of MD in their families.
Consistent with most prior findings in European and US populations, we find that melancholia is a more clinically severe syndrome than nonmelancholic depression with higher rates of comorbidity. The evidence that it is a more “biological” or qualitatively distinct syndrome, however, is mixed.
major depression; melancholia; symptom; stressful life events