Author
Hong Deng
Bio: Hong Deng is an academic researcher from Sichuan University. The author has contributed to research in topics: Major depressive disorder & Positive and Negative Syndrome Scale. The author has an hindex of 11, co-authored 25 publications receiving 1132 citations.
Papers
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University of Oxford1, Virginia Commonwealth University2, Capital Medical University3, Nanjing Medical University4, Hebei Medical University5, Harbin Medical University6, Shantou University7, Sichuan University8, Sun Yat-sen University9, Chongqing University10, Jinan University11, Xi'an Jiaotong University12, Shanxi Medical University13, Zhengzhou University14, Lanzhou University15, Central South University16, Jiangsu University17, Wuhan University18, Zhejiang Chinese Medical University19, China Medical University (PRC)20, Kanazawa Medical University21, Tianjin First Center Hospital22, Tongji University23, Fourth Military Medical University24, Max Planck Society25, Shanghai Jiao Tong University26, Fudan University27, Peking Union Medical College28, University of Copenhagen29, Macau University of Science and Technology30, King Abdulaziz University31, East China Normal University32
TL;DR: 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, two loci contributing to risk of MDD on chromosome 10 are identified: one near the SIRT1 gene and the other in an intron of the LHPP gene.
Abstract: Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene.
745 citations
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Wellcome Trust Centre for Human Genetics1, Chang Gung University2, Max Planck Society3, University of Granada4, University of Cambridge5, National Institute for Health Research6, Sichuan University7, Harbin Medical University8, Zhengzhou University9, China Medical University (PRC)10, Chongqing Medical University11, Nanjing Medical University12, Zhejiang Chinese Medical University13, Capital Medical University14, Hebei Medical University15, Sun Yat-sen University16, Shanxi Medical University17, Jiangsu University18, University of Oxford19, Peking Union Medical College20, Virginia Commonwealth University21, East China Normal University22
TL;DR: It is demonstrated that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state and have important implications for understanding how stress causes the disease.
205 citations
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Wellcome Trust Centre for Human Genetics1, Virginia Commonwealth University2, Shanghai Mental Health Center3, XinHua Hospital4, Shanxi Medical University5, China Medical University (PRC)6, Capital Medical University7, Sun Yat-sen University8, Jiangsu University9, Harbin Medical University10, Chongqing Medical University11, Sichuan University12, Lanzhou University13, Shantou University14, Tongji University15, Jinan University16, Tianjin First Center Hospital17
TL;DR: Three subtypes were most consistently identified in analyses: severe, atypical and non-suicidal, which may represent a pathoplastic variant reflecting Chinese cultural influences.
Abstract: Background Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally? Method Symptoms at their 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. Latent class analysis (LCA) was performed in Mplus. RESULTS; Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct. Conclusions MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
58 citations
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Wellcome Trust Centre for Human Genetics1, Virginia Commonwealth University2, Shanghai Mental Health Center3, XinHua Hospital4, Shanxi Medical University5, China Medical University (PRC)6, Capital Medical University7, Sun Yat-sen University8, Jiangsu University9, Harbin Medical University10, Chongqing Medical University11, Sichuan University12, Lanzhou University13, Shantou University14, Tongji University15, Jinan University16, Tianjin First Center Hospital17
TL;DR: 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 inWestern populations suggest that the results are likely to be broadly representative of the human depressive syndrome.
Abstract: Background 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? Method 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. Results 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. Conclusions 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.
47 citations
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Fudan University1, Shanghai Mental Health Center2, China Medical University (PRC)3, Zhengzhou University4, XinHua Hospital5, Shanxi Medical University6, Capital Medical University7, Sun Yat-sen University8, Jiangsu University9, Harbin Medical University10, Hebei Medical University11, Chongqing Medical University12, Sichuan University13, Lanzhou University14, Shantou University15, Tongji University16, Jinan University17, Wuhan University18, Tianjin First Center Hospital19, Wellcome Trust Centre for Human Genetics20, Clinical Trial Service Unit21, Virginia Commonwealth University22
TL;DR: CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA, and among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes.
Abstract: Background
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?
Method
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.
Results
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.
Conclusions
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.
41 citations
Cited by
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Wellcome Trust Sanger Institute1, University of Michigan2, University of Oxford3, University of Geneva4, University of Exeter5, Greifswald University Hospital6, National Research Council7, University of Bristol8, University of Colorado Boulder9, Fred Hutchinson Cancer Research Center10, University of Washington11, SUNY Downstate Medical Center12, Erasmus University Rotterdam13, University of Trieste14, VU University Amsterdam15, King's College London16, South London and Maudsley NHS Foundation Trust17, University of Edinburgh18, Harvard University19, National Institutes of Health20, Harokopio University21, Innsbruck Medical University22, Broad Institute23, Lund University24, University of Helsinki25, Norwegian University of Science and Technology26, University of Cambridge27, University of Minnesota28, Technische Universität München29, University of North Carolina at Chapel Hill30, University of Toronto31, McGill University32, Leiden University33, University of Pennsylvania34, University of Groningen35, Utrecht University36, Churchill Hospital37
TL;DR: A reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies.
Abstract: We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
2,149 citations
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TL;DR: A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent and significant loci and finds important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia.
Abstract: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
1,898 citations
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15 Sep 2016
TL;DR: An overview of the current evidence of major depressive disorder, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment, is provided.
Abstract: Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment.
1,728 citations
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Royal Edinburgh Hospital1, King's College London2, Centre for Mental Health3, University of Glasgow4, University of Edinburgh5, Medical Research Council6, University of Münster7, University of Melbourne8, University of Freiburg9, University of Queensland10, Harvard University11, Charité12, Broad Institute13, University of North Carolina at Chapel Hill14, Karolinska Institutet15
TL;DR: A genetic meta-analysis of depression found 269 associated genes that highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.
Abstract: Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
1,312 citations
01 Jan 2016
TL;DR: In this article, a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry is presented.
Abstract: We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
1,261 citations