Changchun, China
Changchun, China

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Cai N.,University of Oxford | Bigdeli T.B.,Virginia Commonwealth University | Kretzschmar W.,University of Oxford | Lei Y.,University of Oxford | And 105 more authors.
Nature | Year: 2015

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified2, despite analysis of more than 9,000 cases3. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P= 2.53 × 10-10), the other in an intron of the LHPP gene (P = 6.45 × 10-12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness. © 2015 Macmillan Publishers Limited. All rights reserved.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 56 more.
Type: | Journal: Journal of affective disorders | Year: 2014

The relationship between age at onset (AAO) and major depression (MD) has been studied in US, European and Chinese populations. However, larger sample studies are needed to replicate and extend earlier findings.We re-examined the relationship between AAO and the clinical features of recurrent MD in Han Chinese women by analyzing the phase I (N=1848), phase II (N=4169) and total combined data (N=6017) from the CONVERGE project. Linear, logistic, multiple linear and multinomial logistic regression models were used to determine the association of AAO with continuous, binary and categorical variables.The effect size of the association between AAO and clinical features of MD was quite similar in the phase I and phase II samples. These results confirmed that MD patients with earlier AAO tended to suffer more severe, recurrent and chronic illness and cases of MD with earlier AAO showed increased neuroticism, greater family history and psychiatric comorbidity. In addition, we showed that earlier AAO of MD in Han Chinese women was associated with premenstrual symptoms, postnatal depression, a highly authoritarian or cold childhood parental rearing style and a reduced probability for having melancholia.Data were collected retrospectively through interview and recall bias may have affected the results.MD with earlier AAO in Han Chinese women shows a distinct set of clinical features which are similar to those reported in Western populations.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 56 more.
Type: | Journal: Journal of affective disorders | Year: 2014

Phobic fears are common in the general population and among individuals with major depression (MD). We know little about the prevalence, clinical correlates, and structure of phobic fears in Chinese women with MD.We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used exploratory factor analysis to examine the structure of these phobic fears. We examined the relationship between individual phobic fears and the severity of MD, neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia using logistic regression models.The frequency of phobic fears ranged from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly associated with more severe MD, high neuroticism, and co-morbid panic disorder, generalized anxiety disorder and dysthymia. Our factor analysis suggested four underlying subgroups of phobic fears which differed in their clinical correlates, severity and patterns of comorbidity.Data were collected retrospectively through interview and recall bias may have affected the results.Phobic fears are correlated with comorbid MD and more severe MD. These phobic fears clearly subdivide into four subgroups that differ meaningfully from each other.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 55 more.
Type: Journal Article | Journal: PloS one | Year: 2014

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.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 54 more.
Type: | Journal: Journal of affective disorders | Year: 2015

We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum).Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations.A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2-2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1-1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5-0.8), but more childbirths (OR 1.2).Data were obtained retrospectively through interview and recall bias may have affected the results.MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Shantou University, Hubei University and 54 more.
Type: Journal Article | Journal: Psychological medicine | Year: 2014

The symptoms of major depression (MD) are clinically diverse. Do they form coherent factors that might clarify the underlying nature of this important psychiatric syndrome?Symptoms at lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age 30 years with recurrent DSM-IV MD. Exploratory factor analysis (EFA) and confirmatoryfactor analysis (CFA) were performed in Mplus in random split-half samples.The preliminary EFA results were consistently supported by the findings from CFA. Analyses of the nine DSM-IV MD symptomatic A criteria revealed two factors loading on: (i) general depressive symptoms; and (ii) guilt/suicidal ideation. Examining 14 disaggregated DSM-IV criteria revealed three factors reflecting: (i) weight/appetite disturbance; (ii) general depressive symptoms; and (iii) sleep disturbance. Using all symptoms (n = 27), we identified five factors that reflected: (i) weight/appetite symptoms; (ii) general retarded depressive symptoms; (iii) atypical vegetative symptoms; (iv) suicidality/hopelessness; and (v) symptoms of agitation and anxiety.MD is a clinically complex syndrome with several underlying correlated symptom dimensions. In addition to a general depressive symptom factor, a complete picture must include factors reflecting typical/atypical vegetative symptoms, cognitive symptoms (hopelessness/suicidal ideation), and an agitated symptom factor characterized by anxiety, guilt, helplessness and irritability. Prior cross-cultural studies, factor analyses of MD in Western populations and empirical findings in this sample showing risk factor profiles similar to those seen in Western populations suggest that our results are likely to be broadly representative of the human depressive syndrome.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 56 more.
Type: Journal Article | Journal: PloS one | Year: 2014

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.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Shantou University, Jiangsu University and 54 more.
Type: Journal Article | Journal: PloS one | Year: 2014

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.


PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 55 more.
Type: Journal Article | Journal: PloS one | Year: 2014

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.


PubMed | Ningbo Kang Ning Hospital, King Abdulaziz University, Hebei Medical University, Kangning Hospital and 36 more.
Type: Journal Article | Journal: Current biology : CB | Year: 2015

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individuals somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

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