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Summary Control over the number of mtDNA molecules per cell appears to be tightly regulated, but the mechanisms involved are largely unknown. Reversible alterations in the amount of mtDNA occur in response to stress suggesting that control over the amount of mtDNA is involved in stress-related diseases including major depressive disorder (MDD). Using low-coverage sequence data from 10,442 Chinese women to compute the normalized numbers of reads mapping to the mitochondrial genome as a proxy for the amount of mtDNA, we identified two loci that contribute to mtDNA levels: one within the TFAM gene on chromosome 10 (rs11006126, p value = 8.73 × 10 −28 , variance explained = 1.90%) and one over the CDK6 gene on chromosome 7 (rs445, p value = 6.03 × 10 −16 , variance explained = 0.50%). Both loci replicated in an independent cohort. CDK6 is thus a new molecule involved in the control of mtDNA. We identify increased rates of heteroplasmy in women with MDD, and show from an experimental paradigm using mice that the increase is likely due to stress. Furthermore, at least one heteroplasmic variant is significantly associated with changes in the amount of mtDNA (position 513, p value = 3.27 × 10 −9 , variance explained = 0.48%) suggesting site-specific heteroplasmy as a possible link between stress and increase in amount of mtDNA. These findings indicate the involvement of mitochondrial genome copy number and sequence in an organism’s response to stress. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Discussion 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: 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. Methods: We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60years 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. Results: 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. Limitations: 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. Conclusions: 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. [Copyright &y& Elsevier]

Abstract: Background: 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. Methods: 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. Results: 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%). Limitations: 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. Conclusions: More severe SLEs are more strongly associated with MDD. These results support the involvement of psychosocial adversity in the etiology of MDD in China. [Copyright &y& Elsevier]

Abstract: Background: 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. Methods: We examined the clinical features of 1970 Han Chinese women with DSM-IV major depressive disorder (MDD) between 30 and 60years 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. Results: 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. Conclusions: 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. [Copyright &y& Elsevier]

Background: Anxiety often precedes depression. The anxiety response styles theory of comorbidity suggests anxious individuals with a tendency to ruminate or make hopeless attributions about anxiety symptoms (negative anxiety response styles [NARS]) are more vulnerable to subsequent depressive symptoms. However, this theory has never been tested in adolescence, when the anxiety-depression transition may frequently occur, or using an extended (one-year) follow-up period.Method: 128 early adolescent girls (M=12.39 years) participated with caregivers in a one-year longitudinal study. At baseline and follow-up, participants completed diagnostic interviews and self-report measures assessing child NARS and brooding rumination.Results: T1 NARS predicted longitudinal elevations in depressive symptoms and increased associations between T1 anxiety and T2 depressive symptoms.Limitations: This study examines anxiety and depression comorbidity using a community sample. The sample is relatively low on sociodemographic diversity.Conclusions: Results support the anxiety response styles theory, with potential implications for early identification of anxious youth at risk for later development of comorbid depression. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: 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. Methods: We examined a large-scale clinical study of Chinese Han women with recurrent major depression and community-acquired controls. Results: 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). Limitations: 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. Conclusions: 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. [Copyright &y& Elsevier]