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Cai N.,University of Oxford | Chang S.,Chang Gung University | Li Y.,University of Oxford | Li Q.,BGI Shenzhen | And 70 more authors.
Current Biology

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 individual's 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. © 2015 Elsevier Ltd All rights reserved. Source

Yang F.,Shanghai JiaoTong University | Zhao H.,Zhejiang Traditional Chinese Medical Hospital | Wang Z.,Jiangsu University | Tao D.,Xinhua Hospital of Zhejiang Province | And 57 more authors.
Journal of Affective Disorders

Background 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. Methods 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. Results 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. Limitations Data were collected retrospectively through interview and recall bias may have affected the results. Conclusions MD with earlier AAO in Han Chinese women shows a distinct set of clinical features which are similar to those reported in Western populations. © 2014 Published by Elsevier B.V. Source

Zhu Y.,Liaoning Medical University | Zhang H.,Liaoning Medical University | Shi S.,Shanghai Mental Health Center | Shi S.,Fudan University | And 60 more authors.

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. © 2013 Zhu et al. Source

Li Y.,Oxford Genetics | Aggen S.,Virginia Commonwealth University | Shi S.,Shanghai Mental Health Center | Shi S.,Fudan University | And 58 more authors.
Psychological Medicine

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. © Cambridge University Press 2014. Source

Wu W.,Jiangsu University | Wang Z.,Jiangsu University | Wei Y.,Jiangsu University | Zhang G.,Jiangsu University | And 62 more authors.

Background: 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. Results: 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. Conclusions: 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. © 2013 Wu et al. Source

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