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1.  A comparison of the clinical characteristics of Chinese patients with recurrent major depressive disorder with and without dysthymia☆ 
Journal of Affective Disorders  2011;135(1-3):106-110.
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.
PMCID: PMC3221043  PMID: 21824660
Major depressive disorder; Dysthymia; Symptom; Comorbidity
2.  Age at onset of major depressive disorder in Han Chinese women: Relationship with clinical features and family history☆ 
Journal of Affective Disorders  2011;135(1-3):89-94.
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.
PMCID: PMC3210897  PMID: 21782247
Major depressive disorder; Age at onset; Symptom; Comorbidity
3.  Clinical features and risk factors for post-partum depression in a large cohort of Chinese women with recurrent major depressive disorder 
Journal of Affective Disorders  2012;136(3):983-987.
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.
PMCID: PMC3315022  PMID: 21824665
Postpartum depression; Major depressive disorder; Neuroticism; Anxiety disorder
4.  Clinical Features of Patients with Dysthymia in a Large Cohort of Han Chinese Women with Recurrent Major Depression 
PLoS ONE  2013;8(12):e83490.
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.
PMCID: PMC3873934  PMID: 24386213
5.  Examining the relationship between lifetime stressful life events and the onset of major depression in Chinese women☆ 
Journal of Affective Disorders  2011;135(1-3):95-99.
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.
PMCID: PMC3210899  PMID: 21821294
Major depressive disorder; Stressful life event; Social adversity; Symptom
6.  Associations of Educational Attainment, Occupation, Social Class and Major Depressive Disorder among Han Chinese Women 
PLoS ONE  2014;9(1):e86674.
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.
Principal findings
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.
PMCID: PMC3909008  PMID: 24497966
7.  The relationship between neuroticism, major depressive disorder and comorbid disorders in Chinese women 
Journal of Affective Disorders  2011;135(1-3):100-105.
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.
PMCID: PMC3220767  PMID: 21824661
Major depressive disorder; Anxiety disorders; Neuroticism
8.  Patterns of co-morbidity with anxiety disorders in Chinese women with recurrent major depression 
Psychological Medicine  2011;42(6):1239-1248.
Studies conducted in Europe and the USA have shown that co-morbidity between major depressive disorder (MDD) and anxiety disorders is associated with various MDD-related features, including clinical symptoms, degree of familial aggregation and socio-economic status. However, few studies have investigated whether these patterns of association vary across different co-morbid anxiety disorders. Here, using a large cohort of Chinese women with recurrent MDD, we examine the prevalence and associated clinical features of co-morbid anxiety disorders.
A total of 1970 female Chinese MDD patients with or without seven co-morbid anxiety disorders [including generalized anxiety disorder (GAD), panic disorder, and five phobia subtypes] were ascertained in the CONVERGE study. Generalized linear models were used to model association between co-morbid anxiety disorders and various MDD features.
The lifetime prevalence rate for any type of co-morbid anxiety disorder is 60.2%. Panic and social phobia significantly predict an increased family history of MDD. GAD and animal phobia predict an earlier onset of MDD and a higher number of MDD episodes, respectively. Panic and GAD predict a higher number of DSM-IV diagnostic criteria. GAD and blood-injury phobia are both significantly associated with suicidal attempt with opposite effects. All seven co-morbid anxiety disorders predict higher neuroticism.
Patterns of co-morbidity between MDD and anxiety are consistent with findings from the US and European studies; the seven co-morbid anxiety disorders are heterogeneous when tested for association with various MDD features.
PMCID: PMC3339636  PMID: 22126712
Co-morbid anxiety disorders; major depression
9.  A comparison of the clinical characteristics of women with recurrent major depression with and without suicidal symptomatology 
Psychological Medicine  2012;42(12):2591-2598.
The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms.
We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD.
Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9–6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt.
This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.
PMCID: PMC3488812  PMID: 22716960
Co-morbidity; major depression; suicidal ideation; suicide; women
10.  Prospective, population-based study of the transition from major depressive disorder to bipolar disorder 
It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder.
We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions.
Approximately 1 in 20 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, Black race/ethnicity, and less than high school education. Clinical characteristics of depression (e.g., age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (Odds Ratio=2.20; 95% Confidence Interval=1.47, 3.30) and generalized anxiety disorder (OR=1.58; CI=1.06, 2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR=1.26; CI=1.12, 1.42) and past-year problems with one's social support group (OR=1.79; CI=1.19, 2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest.
A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD, and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder.
PMCID: PMC3703739  PMID: 22394428
unipolar; bipolar; depression; mania; epidemiology
11.  Psychosocial Features Associated with Lifetime Comorbidity of Major Depression and Anxiety Disorders Among a Community Sample of Mid-Life Women: The SWAN Mental Health Study 
Depression and anxiety  2012;29(12):1050-1057.
In clinical samples, comorbidity between depressive and anxiety disorders is associated with greater symptom severity and elevated suicide risk. Less is known, however, regarding the long-term psychosocial impact that a lifetime history of both MDD and one or more anxiety disorders has in community samples. This report evaluates clinical, psychological, social, and stress-related characteristics associated with a lifetime history of MDD and anxiety.
Data from 915 women aged 42–52 who were recruited as part of the the Study of Women's Health Across the Nation Mental Health Study were used to examine clinical and psychosocial features across groups of women with a SCID-diagnosed lifetime history of MDD alone, anxiety alone, both MDD and anxiety, or neither MDD nor anxiety.
As compared with women with a history of either MDD or anxiety alone, women with a comorbid history were more likely to report recurrent MDD, multiple and more severe lifetime anxiety disorders, greater depressive and anxiety symptoms, diminished social support, and more past-year distressing life events. Exploratory analyses indicated that women with a comorbid history also report more childhood abuse/neglect and diminished self-esteem, as compared with women with a history of either disorder alone.
Midlife women with a comorbid history that includes both MDD and anxiety disorders report diminished social support, more symptomatic distress, and a more severe and recurrent psychiatric history. Future research is needed to clarify the biological and psychosocial risk factors associated with this comorobid profile, and to develop targeted interventions for this at-risk group.
PMCID: PMC3592574  PMID: 22930404
major depressive disorder; anxiety disorders; comorbidity; child abuse; social support; stress, psychological
Depression and Anxiety  2011;29(1):10-15.
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.
PMCID: PMC3429856  PMID: 22065525
major depression; family history; symptom; life events
13.  Cognitive trio: relationship with major depression and clinical predictors in Han Chinese women 
Psychological Medicine  2013;43(11):2265-2275.
Previous studies support Beck's cognitive model of vulnerability to depression. However, the relationship between his cognitive triad and other clinical features and risk factors among those with major depression (MD) has rarely been systematically studied.
The three key cognitive symptoms of worthlessness, hopelessness and helplessness were assessed during their lifetime worst episode in 1970 Han Chinese women with recurrent MD. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.
Compared to patients who did not endorse the cognitive trio, those who did had a greater number of DSM-IV A criteria, more individual depressive symptoms, an earlier age at onset, a greater number of episodes, and were more likely to meet diagnostic criteria for melancholia, postnatal depression, dysthymia and anxiety disorders. Hopelessness was highly related to all the suicidal symptomatology, with ORs ranging from 5.92 to 6.51. Neuroticism, stressful life events (SLEs) and a protective parental rearing style were associated with these cognitive symptoms.
During the worst episode of MD in Han Chinese women, the endorsement of the cognitive trio was associated with a worse course of depression and an increased risk of suicide. Individuals with high levels of neuroticism, many SLEs and high parental protectiveness were at increased risk for these cognitive depressive symptoms. As in Western populations, symptoms of the cognitive trio appear to play a central role in the psychopathology of MD in Chinese women.
PMCID: PMC3807662  PMID: 23425530
Cognitive trio; Han Chinese women; major depression; suicide; symptoms
14.  Prepregnancy body mass index, gestational weight gain and the likelihood of major depression during pregnancy 
The Journal of clinical psychiatry  2009;70(9):1290-1296.
We assessed the relation between prepregnancy body mass index (BMI) and the likelihood of major depressive disorder (MDD) during pregnancy and test whether this association was modified by gestational weight gain.
Women (n=242) were enrolled at <20 weeks gestation into a prospective cohort study. Diagnosis of MDD was made with the Structured Clinical Interview for DSM-IV at 20, 30, and 36 weeks. Gestational weight gain was compared with the 1990 Institute of Medicine weight gain recommendations. To assess the independent association between prepregnancy BMI and the odds of MDD, MDD at each time point was used as the dependent measure in a multivariable longitudinal logistic regression model employing generalized estimating equations.
There was a strong, positive dose-response association between prepregnancy BMI and the likelihood of MDD (p=0.002). Compared with a BMI of 18, the adjusted odds ratios (95% confidence interval) for BMIs of 23, 28, and 33 were 1.4 (1.1, 1.7), 1.9 (1.3, 2.9), and 2.6 (1.4, 4.3), respectively. Gestational weight gain significantly modified this effect. Among women with weight gains within and above the 1990 IOM recommendations, pregravid overweight was associated with a greater likelihood of major depression. In contrast, all women with weight gains below recommended levels had an elevated odds of depression, regardless of their pregravid BMI (p<0.05).
Because pregravid overweight, poor gestational weight gain, and major depression all pose substantial risks for fetal development and birth outcomes, health care providers should monitor depression levels in these women to facilitate appropriate depression intervention.
PMCID: PMC2760651  PMID: 19607761
15.  Single versus Recurrent Depression History: Differentiating risk-factors among current U.S. Smokers 
Drug and alcohol dependence  2010;109(1-3):90-95.
The strong relationship between persistent tobacco use and Major Depressive Disorder (MDD) has motivated clinical trials of specialized treatments targeting smokers with a history of MDD. Meta-analyses suggest positive responses to specialized treatments have been observed consistently among smokers with history of recurrent rather than a single episode of MDD. Approximately 15% of current US smokers have a history of recurrent MDD. Little is known about the risk factors that contribute to persistent smoking and differentiate these at-risk smokers. US.
The National Comorbidity Survey – Replication (NCS-R) included a survey of 1560 smokers participants aged 18 and older in the United States. Lifetime history of MDD was categorized according to chronicity: No History (No MDD), single episode (MDD-S) and recurrent depression (MDD-R). The relationship between the chronicity of MDD, smoking characteristics, cessation history, nicotine dependence, comorbidity with psychiatric disorders, and current functional impairments were examined.
MDD-R smokers reported fewer lifetime cessation efforts, smoked more cigarettes, had higher levels of nicotine dependence, had higher rates of co-morbid psychiatric disorders and greater functional impairment than smokers with No MDD. MDD-S smokers were not consistently distinguished from No MDD smokers on cessation attempts, level of daily smoking, nicotine dependence or functional impairment indices.
The study highlights the importance of chronicity when characterizing depression related risk of persistent smoking behavior. Although, clinical trials suggest MDD-R smokers specifically benefit from specialized behavioral treatments, these services are not widely available and more efforts are needed to engage MDD-R smokers in efficacious treatments. Abstract Word Count: 249
PMCID: PMC2890270  PMID: 20074868
Smoking; Depression; Recurrent Depression; Nicotine Dependence; Item
16.  A Neuropeptide Y Variant (rs16139) Associated with Major Depressive Disorder in Replicate Samples from Chinese Han Population 
PLoS ONE  2013;8(2):e57042.
This study aimed to investigate the single nucleotide polymorphisms (SNPs) of neuropeptide Y (NPY) and major depressive disorder (MDD) in Chinese Han population.
Prospective and randomized studies were carried out.
A total of 700 patients (324 male and 376 female; mean age = 40±14.9 years) with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls (313 male and 360 female; mean age = 41.9±17.2 years) were used to investigate the relationship between SNPs of NPY and the pathogenesis of MDD. A total of 417 patients (195 male and 202 female; mean age = 36±14.2 years) diagnosed with MDD and 314 healthy controls (153 male and 161 female; mean age = 37.9±14.2 years) from Chinese Han population were used to verify the relationship between SNPs of NPY and the pathogenesis of MDD.
Intervention and outcome
Ligase detection reactions were performed to detect the SNP sites of NPY. A series of statistical methods was carried out to investigate the correlation between the NPY gene SNP and MDD.
Statistical analysis showed a significant correlation between the SNP sites rs16139 in NPY and the morbidity of depression. Patients with MDD have a lower frequency of A-allele in rs16139 in replicate samples from Chinese Han population. However, the frequency varied between male and female patients.
The gene polymorphism loci rs16139 was closely related to MDD in Chinese Han population.
PMCID: PMC3584142  PMID: 23468908
17.  Clinical features and correlates of major depressive disorder in individuals with body dysmorphic disorder 
Journal of affective disorders  2006;97(1-3):129-135.
Body dysmorphic disorder (BDD) and major depressive disorder (MDD) appear highly comorbid. However, MDD in individuals with BDD has received little investigation.
The prevalence and characteristics of comorbid MDD were assessed in 178 BDD subjects. BDD subjects with current comorbid MDD (n=68) were compared to BDD subjects without current comorbid MDD (n=96) on demographic and clinical characteristics. Predictors of current MDD were determined using logistic regression.
74.2% of subjects had lifetime MDD, and 38.2% had current MDD. The melancholic subtype was most common, and a majority of depressed subjects had recurrent episodes. Mean onset of BDD occurred at a younger age than MDD. Subjects with current comorbid MDD had many similarities to those without MDD, although those with comorbid MDD had more severe BDD. Subjects with comorbid MDD were also more likely to have an anxiety or personality disorder, as well as a family history of MDD. They also had greater social anxiety, suicidality, and poorer functioning and quality of life. Current MDD was independently predicted by a personality disorder and more severe BDD.
It is unclear how generalizable the results are to the community or to subjects ascertained for MDD who have comorbid BDD. The study lacked a comparison group such as MDD subjects without BDD.
MDD is common in individuals with BDD. Individuals with current MDD had greater morbidity in some clinically important domains, including suicidality, functioning, and quality of life. A personality disorder and more severe BDD independently predicted the presence of current MDD.
PMCID: PMC1741857  PMID: 16893571
Body dysmorphic disorder; Dysmorphophobia; Depression; Mood disorders; Affective disorders; Somatoform disorders
18.  The Oft-Neglected Role of Parietal EEG Asymmetry and Risk for Major Depressive Disorder 
Psychophysiology  2011;48(1):82-95.
Relatively less right parietal activity may reflect reduced arousal and signify risk for major depressive disorder (MDD). Inconsistent findings with parietal electroencephalographic (EEG) asymmetry, however, suggest issues such as anxiety comorbidity and sex differences have yet to be resolved. Resting parietal EEG asymmetry was assessed in 306 individuals (31% male) with (n = 143) and without (n = 163) a DSM-IV diagnosis of lifetime MDD and no comorbid anxiety disorders. Past MDD+ women displayed relatively less right parietal activity than current MDD+ and MDD- women, replicating prior work. Recent caffeine intake, an index of arousal, moderated the relationship between depression and EEG asymmetry for women and men. Findings suggest that sex differences and arousal should be examined in studies of depression and regional brain activity.
PMCID: PMC3000438  PMID: 20525011
19.  Incident and Recurrent Major Depressive Disorder and Coronary Artery Disease Severity in Acute Coronary Syndrome Patients 
Journal of psychiatric research  2007;42(8):670-675.
There is recent evidence that acute coronary syndrome (ACS) patients with first time incident major depressive disorder (MDD) and those with recurrent MDD represent different subtypes among individuals with ACS and comorbid depression. However, few studies have examined whether or not these subtypes differ in coronary artery disease (CAD) severity. We assessed whether those with incident MDD (in-hospital MDD and negative for history of MDD) or recurrent MDD (in-hospital MDD and a positive history of MDD) differ in angiographically documented CAD severity. Within 1 week of admission for ACS, 88 patients completed a clinical interview to assess current and past diagnosis of MDD. CAD severity was assessed in all patients by coronary angiography. A hierarchical regression analysis showed that neither in-hospital MDD status, nor history of MDD were significant predictors of CAD severity, but the interaction term between in-hospital MDD status and history of MDD was a significant predictor of CAD severity, after controlling for age, sex and ethnicity. Follow-up analyses showed that patients with first-time, incident MDD had significantly more severe CAD compared to patients with recurrent MDD (p = 0.043). To conclude, our study adds to the growing evidence that patients with incident MDD should be considered as a clinically distinct subtype from those with recurrent MDD. Possible mechanisms for differing CAD severity by angiogram between these two subtypes are proposed and implications for prognosis and treatment are discussed.
PMCID: PMC2398720  PMID: 17709116
Acute Coronary Syndrome; Coronary Artery Disease; Myocardial Infarction; Angiogram; Incident Major Depressive Disorder; Recurrent Major Depressive Disorder
20.  The role of fear and anxiety in the familial risk for major depression: a three-generation study 
Psychological medicine  2008;38(11):1543-1556.
The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression.
Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD.
In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns.
These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.
PMCID: PMC2904071  PMID: 18275630
Anxiety; depression; fear; mediator; multi-generation
21.  Characterization of major depressive disorder using a multiparametric classification approach based on high resolution structural images 
Major depressive disorder (MDD) is one of the most disabling mental illnesses. Previous neuroanatomical studies of MDD have revealed regional alterations in grey matter volume and density. However, owing to the heterogeneous symptomatology and complex etiology, MDD is likely to be associated with multiple morphometric alterations in brain structure. We sought to distinguish first-episode, medication-naive, adult patients with MDD from healthy controls and characterize neuroanatomical differences between the groups using a multiparameter classification approach.
We recruited medication-naive patients with first-episode depression and healthy controls matched for age, sex, handedness and years of education. High-resolution T1-weighted images were used to extract 7 morphometric parameters, including both volumetric and geometric features, based on the surface data of the entire cerebral cortex. These parameters were used to compare patients and controls using multivariate support vector machine, and the regions that informed the discrimination between the 2 groups were identified based on maximal classification weights.
Thirty-two patients and 32 controls participated in the study. Both volumetric and geometric parameters could discriminate patients with MDD from healthy controls, with cortical thickness in the right hemisphere providing the greatest accuracy (78%, p ≤ 0.001). This discrimination was informed by a bilateral network comprising mainly frontal, temporal and parietal regions.
The sample size was relatively small and our results were based on first-episode, medication-naive patients.
Our investigation demonstrates that multiple cortical features are affected in medication-naive patients with first-episode MDD. These findings extend the current understanding of the neuropathological underpinnings of MDD and provide preliminary support for the use of neuroanatomical scans in the early detection of MDD.
PMCID: PMC3937284  PMID: 24083459
22.  The Relationship between Childhood Trauma History and the Psychotic Subtype of Major Depression 
Acta psychiatrica Scandinavica  2009;121(6):462-470.
Increasing evidence exists linking childhood trauma and primary psychotic disorders, but there is little research on patients with primary affective disorders with psychotic features.
The sample consisted of adult outpatients diagnosed with Major Depressive Disorder (MDD) at clinic intake using a structured clinical interview. Patients with MDD with (n = 32) versus without psychotic features (n = 591) were compared as to their rates of different types of childhood trauma.
Psychotic MDD patients were significantly more likely to report histories of physical (OR = 2.81) or sexual abuse (OR = 2.75) compared with nonpsychotic MDD patients. These relationships remained after controlling for baseline differences. Within the subsample with comorbid posttraumatic stress disorder, patients with psychotic MDD were significantly more likely to report childhood physical abuse (OR = 3.20).
Results support and extend previous research by demonstrating that the relationship between childhood trauma and psychosis is found across diagnostic groups.
PMCID: PMC3671385  PMID: 19764926
major depression; childhood trauma; psychosis; posttraumatic stress disorder
23.  Prevalence and natural course of late-life depression in China primary care: A population based study from an urban community 
Journal of affective disorders  2012;141(1):86-93.
Primary care is the most promising venue for the management of late-life depression in China. The current study was designed to establish the prevalence of major depressive disorder among older adults in primary care, and to examine the correlates, and the natural course of late-life depression over a year.
A sample of 1275 adults aged over 60 years was recruited from a primary care clinic in urban China for screening with PHQ-9, and 262 participants stratified by PHQ-9 score were interviewed to collect the presence of major depressive disorder (MDD), the availability of social support, and physical health and functional status. Participants were followed up for 12 months at 3-month intervals.
The estimated prevalence of MDD was 11.3% with the SCID interview. Increasing age, female gender, and lower educational level, living alone, low support from family, high medical illness burden, and impairment of daily function were significantly associated with MDD in later life. Less than 1% of these patients received treatments. More than 60% of patients with MDD at baseline remained depressed throughout the 12 month follow-up period; and only 3 patients had been treated during the 12-month follow-up.
The correlates of late-life depression observed here may not necessarily serve as risk factors guiding the development of future prevention strategies.
In an urban Chinese primary care setting, late-life depression was found to be a common condition. Few patients with MDD received treatment for their condition, and the majority remained depressed over the following year.
PMCID: PMC3566241  PMID: 22464006
Late-life depression; Chinese primary care; Prevalence; Correlates; Natural course
24.  An exploratory factor analysis of nutritional biomarkers associated with major depression in pregnancy 
Public health nutrition  2011;15(6):1078-1086.
Major depressive disorder (MDD) during pregnancy increases the risk of adverse maternal and infant outcomes. Maternal nutritional status may be a modifiable risk factor for antenatal depression. We evaluated the association between patterns in mid-pregnancy nutritional biomarkers and MDD.
Prospective cohort study
Pittsburgh, Pennsylvania, USA
Women who enrolled at ≤20 weeks gestation had a diagnosis of MDD made with the Structured Clinical Interview for DSM-IV at 20-, 30-, and 36-week study visits. A total of 135 women contributed 345 person-visits. Non-fasting blood drawn at enrollment was assayed for red cell essential fatty acids, plasma folate, homocysteine, and ascorbic acid; serum 25-hydroxyvitamin D, retinol, vitamin E, carotenoids, ferritin, and soluble transferrin receptors. Nutritional biomarkers were entered into principal components analysis.
Three factors emerged: Factor 1, Essential Fatty Acids; Factor 2, Micronutrients; and Factor 3, Carotenoids. MDD was prevalent in 21.5% of women. In longitudinal multivariable logistic models, there was no association between the Essential Fatty Acid or Micronutrient patterns and MDD either before or after adjustment for employment, education, or prepregnancy BMI. In unadjusted analysis, women with Carotenoid factor scores in the middle and upper tertiles were 60% less likely than women in the bottom tertile to have MDD during pregnancy, but after adjustment for confounders, the associations were no longer statistically significant.
While meaningful patterns were derived using nutritional biomarkers, significant associations with MDD were not observed in multivariable adjusted analyses. Larger, more diverse samples are needed to understand nutrition-depression relationships during pregnancy.
PMCID: PMC3309065  PMID: 22152590
diet patterns; biomarkers; pregnancy; depression
25.  Exploring Age of Onset as a Causal Link between Major Depression and Nonmedical Use of Prescription Medications 
Drug and alcohol dependence  2011;120(1-3):99-104.
Nonmedical use of prescription medications (NUPM) has been associated with major depression (MDD), but the specific processes by which they might interact and influence one another are understudied. This investigation attempted to clarify the relationship between MDD and NUPM by examining whether age of MDD onset influenced current and past NUPM and by examining whether age of NUPM onset influenced lifetime or past year MDD.
These goals were met though use of data from the 2005–2007 National Survey on Drug Use and Health. Analyses utilized design-based logistic regression, and current age and order of MDD onset and NUPM initiation were examined in interactions with age of MDD or NUPM onset.
For each year MDD onset was delayed, odds of lifetime, past year, past 30-day NUPM and substance dependence from NUPM were decreased by 2.3%, 2.6%, 1.9% and 2.3%, respectively. Earlier NUPM onset increased odds of past year (3.8%) and lifetime MDD (4.3%) in young adults, and lifetime MDD (2.5%) in the 26–34 age group. Current age also interacted with age of MDD onset, with effects on NUPM pronounced in the 65 and older cohort. Order of MDD/NUPM onset generally did not interact with age of MDD onset, but it did interact with age of NUPM onset; the effects of NUPM onset on past year MDD were only significant in those with NUPM first.
These results highlight the need for further investigations of the interactions between depression and NUPM, particularly to evaluate potential causal relationships.
PMCID: PMC3206988  PMID: 21802221
Nonmedical prescription use; Major Depression; Age of Onset; Etiology

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