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1.  Major depression and the metabolic syndrome 
The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM-III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.
doi:10.1375/twin.13.4.347
PMCID: PMC3150840  PMID: 20707705
Depressive disorder; major; Metabolic syndrome; Cardiovascular diseases
2.  Waist Circumference, Not the Metabolic Syndrome, Predicts Glucose Deterioration in Type 2 Diabetes 
Obesity (Silver Spring, Md.)  2008;16(4):869-874.
We sought to assess the relationship between the metabolic syndrome, abdominal obesity, and glucose deterioration amongst patients with type 2 diabetes. Our prospective cohort consisted of 164 adult patients with established diabetes who have a history of poor glycemic control, have just completed an intensive intervention aimed at improved control, and have demonstrated reduced HbA1c prior to enrollment. Waist circumference and presence of metabolic syndrome were assessed at baseline, and patients were followed-up (median 24 months) for assessment of the study outcome, time-to-hyperglycemic relapse, pre-defined as HbA1c >8% and >1% rise over baseline. Kaplan-Meier estimates of relapse-free survival and multivariable Cox regression models were used to quantify the independent effects of the metabolic syndrome and waist circumference on risk of glucose deterioration. Baseline waist circumference was 42.9 ± 5.5 inches. Prevalence of the metabolic syndrome was 80%. During follow-up, 39 patients (24%) experienced hyperglycemic relapse. The metabolic syndrome was not associated with time-to-relapse (p=0.15). The waist circumference component alone however was associated with increased likelihood of hyperglycemic relapse with an unadjusted hazard ratio of 3.4 (95% CI 1.2 – 9.7) and a hazard ratio of 3.2 (95% CI 1.1 – 9.1) after adjusting for age, gender, insulin use, weight change, and physical activity level. The NCEP ATPIII metabolic syndrome had limited ability to predict glucose deterioration in this type 2 diabetes cohort. Waist circumference alone, however, is a strong predictor of future glucose control and may be a parsimonious tool for risk stratification. BMI may also be a useful predictive tool.
OBJECTIVE
To assess the relationship between the metabolic syndrome, abdominal obesity, and glucose deterioration amongst patients with type 2 diabetes.
METHODS AND PROCEDURES
Our prospective cohort consisted of 164 adult patients with established type 2 diabetes who have a history of poor glycemic control, have just completed an intensive intervention aimed at improved control, and have demonstrated reduced HbA1c prior to enrollment. Waist circumference and presence of metabolic syndrome were assessed at baseline, and patients were followed-up (median 24 months) for assessment of the study outcome, time-to-hyperglycemic relapse, pre-defined as HbA1c >8% and >1% rise over baseline. Kaplan-Meier estimates of relapse-free survival and multivariable Cox regression models were used to quantify the independent effects of the metabolic syndrome and waist circumference on risk of glucose deterioration.
RESULTS
Baseline waist circumference was 42.9 ± 5.5 inches. Prevalence of the metabolic syndrome was 80%. During follow-up, 39 patients (24%) experienced hyperglycemic relapse. The metabolic syndrome was not associated with time-to-relapse (p=0.15). The waist circumference component alone however was associated with increased likelihood of hyperglycemic relapse with an unadjusted hazard ratio of 3.4 (95% CI 1.2 – 9.7) and a hazard ratio of 3.2 (95% CI 1.1 – 9.1) after adjusting for age, gender, insulin use, weight change, and physical activity level.
CONCLUSION
The NCEP ATPIII metabolic syndrome had limited ability to predict glucose deterioration in this type 2 diabetes cohort. Waist circumference alone, however, is a strong predictor of future glucose control and may be a parsimonious tool for risk stratification. BMI may also be a useful predictive tool.
doi:10.1038/oby.2008.12
PMCID: PMC4131716  PMID: 18277389
Glucose Control; Insulin Resistance; metabolic syndrome components; BMI; obesity
3.  Predictors of first lifetime episodes of major depression in midlife women 
Psychological medicine  2008;39(1):55-64.
Background
Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition.
Method
The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses.
Results
Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression.
Conclusions
Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife.
doi:10.1017/S0033291708003218
PMCID: PMC2905863  PMID: 18377672
Incident major depression; longitudinal study; menopause; midlife women
4.  Childhood Physical Abuse Is Associated with Incident Metabolic Syndrome in Mid-Life Women 
Objective
Previous research has suggested that childhood emotional abuse, physical abuse, and sexual abuse are associated with an increased risk for ischemic heart disease. Our objective was to examine whether childhood abuse predicted incident metabolic syndrome, a precursor to heart disease, in mid-life women.
Methods
Participants were 342 (114 Black, 228 White) women from the Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN). SWAN included a baseline assessment of premenopausal or early perimenopausal women in midlife (mean age = 45.7), and women were evaluated for presence of the metabolic syndrome over 7 annual follow-up visits. Women were classified as having metabolic syndrome if they met 3 of the following criteria: waist circumference > 88 cm, triglycerides ≥ 150 mg/dl, HDL < 50 mg/dl, SBP ≥ 130 or DBP ≥ 85 mmHg or on blood pressure medication, and fasting glucose ≥ 110 mg/dl or diabetic. The Childhood Trauma Questionnaire is a standardized measure that retrospectively assesses three domains of abuse in childhood and adolescence: emotional, physical, and sexual abuse.
Results
Approximately 34% of the participants reported a history of abuse. Cox model survival analysis showed that physical abuse was associated with incident metabolic syndrome over the course of seven years (HR = 2.12, p = .02), adjusted for ethnicity, age at baseline, and time-dependent menopausal status. Sexual abuse and emotional abuse were unrelated to the metabolic syndrome.
Conclusion
This is the first study to show that a history of childhood abuse, specifically physical abuse, is related to the development of metabolic syndrome in mid-life women.
doi:10.1037/a0027891
PMCID: PMC3641896  PMID: 22775234
childhood abuse; metabolic syndrome; menopause
5.  Relative Androgen Excess During the Menopausal Transition Predicts Incident Metabolic Syndrome in Mid-Life Women: SWAN 
Menopause (New York, N.Y.)  2009;16(2):257-264.
Background
During the menopausal transition, total testosterone remains unchanged while estrogen decreases markedly creating a state of relative androgen excess. We hypothesized that change in the testosterone/estradiol (T/E) ratio during the menopausal transition would be associated with incident metabolic syndrome.
Methods and Results
The association between incident metabolic syndrome and total estradiol, total testosterone, sex hormone binding globulin, the free androgen index (FAI), baseline ratio of total testosterone over total estradiol and the change of this ratio over time was evaluated in a multiethnic cohort of 1,862 pre- and perimenopausal women without diabetes enrolled in the Study of Women’s Health Across the Nation (SWAN). New cases (n=257) of the metabolic syndrome were identified in the cohort during 6296 woman-years of follow-up. The age adjusted total T/E ratio increased 10.1% per year during the 5 years of follow-up. Neither baseline nor change in estradiol were associated with incident metabolic syndrome. Low sex hormone biding globulin, free androgen index and high total testosterone at baseline all increased the risk of metabolic syndrome but their change over time did not. Both baseline total T/E ratio (1.41; 95% CI=1.17-1.1.69; P 0.001) and its rate of change (1.24; 95% CI=1.01-1.52; P 0.04) were associated with increased incident metabolic syndrome independent of ethnicity.
Conclusions
The interaction between testosterone and estradiol during the menopausal transition, rather than the individual change of each over time, is a factor in determination of risk for developing the metabolic syndrome during the menopausal transition. This relationship was independent of ethnicity and other factors associated with prevalent metabolic syndrome prior to the onset of the menopausal transition.
doi:10.1097/gme.0b013e318185e249
PMCID: PMC2950016  PMID: 18971793
Menopause; Testosterone; Estrogen; Metabolic; Syndrome
6.  Two-Year Prospective Study of Major Depressive Disorder in HIV-Infected Men 
Journal of affective disorders  2007;108(3):225-234.
Objective
The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV−) risk-group controls (N=90).
Method
By design participants at entry were without current major depression, substance dependence or major anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging, life events, and psychiatric assessments (Structured Clinical Interview for DSM III-R) were conducted semi-annually for those with AIDS, and annually for all others.
Results
Lifetime prevalence of major depression or other psychiatric disorder did not differ at baseline between HIV+ men and controls. On 2-year follow up those with symptomatic HIV disease were significantly more likely to experience a major depressive episode than were asymptomatic HIV+ individuals and HIV− controls (p<0.05). Episodes were as likely to be first onset as recurrent depression. After baseline disease stage and medical variables associated with HIV infection were controlled, a lifetime history of major depression, or of lifetime psychiatric co-morbidity (two or more psychiatric disorders), predicted subsequent major depressive episode (p <0.05). Neither HIV disease progression during follow-up, nor the baseline presence of neurocognitive impairment, clinical brain imaging abnormality, or marked life adversity predicted a later major depressive episode.
Limitations
Research cohort of men examined before era of widespread use of advanced anti-HIV therapies.
Conclusions
Symptomatic HIV disease, but not HIV infection itself, increases intermediate-term risk of major depression. Prior psychiatric history most strongly predicted future vulnerability.
doi:10.1016/j.jad.2007.10.017
PMCID: PMC2494949  PMID: 18045694
7.  Major Depression During and After the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN) 
Psychological medicine  2011;41(9):1879-1888.
Background
It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to premenopause.
Objectives
To examine whether the odds of experiencing major depression were greater when women were perimenopausal or postmenopausal compared to when they were premenopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms, serum levels or changes in estradiol, follicular stimulating hormone, or testosterone and relevant confounders.
Methods
Participants included the 221 African American and Caucasian women, aged 42–52, who were premenopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women’s Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual, and current major depression at baseline and annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones were obtained annually.
Results
Women were two to four times more likely to experience major depression episode when they were perimenopausal or early postmenopausal. Repeated measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, vasomotor symptoms and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study.
Conclusions
The risk of major depression is greater for women during and immediately after the menopausal transition than when they are premenopausal.
doi:10.1017/S003329171100016X
PMCID: PMC3584692  PMID: 21306662
8.  Intimate Partner Violence and Incident Depressive Symptoms and Suicide Attempts: A Systematic Review of Longitudinal Studies 
PLoS Medicine  2013;10(5):e1001439.
Karen Devries and colleagues conduct a systematic review of longitudinal studies to evaluate the direction of association between symptoms of depression and intimate partner violence.
Please see later in the article for the Editors' Summary
Background
Depression and suicide are responsible for a substantial burden of disease globally. Evidence suggests that intimate partner violence (IPV) experience is associated with increased risk of depression, but also that people with mental disorders are at increased risk of violence. We aimed to investigate the extent to which IPV experience is associated with incident depression and suicide attempts, and vice versa, in both women and men.
Methods and Findings
We conducted a systematic review and meta-analysis of longitudinal studies published before February 1, 2013. More than 22,000 records from 20 databases were searched for studies examining physical and/or sexual intimate partner or dating violence and symptoms of depression, diagnosed major depressive disorder, dysthymia, mild depression, or suicide attempts. Random effects meta-analyses were used to generate pooled odds ratios (ORs). Sixteen studies with 36,163 participants met our inclusion criteria. All studies included female participants; four studies also included male participants. Few controlled for key potential confounders other than demographics. All but one depression study measured only depressive symptoms. For women, there was clear evidence of an association between IPV and incident depressive symptoms, with 12 of 13 studies showing a positive direction of association and 11 reaching statistical significance; pooled OR from six studies = 1.97 (95% CI 1.56–2.48, I2 = 50.4%, pheterogeneity = 0.073). There was also evidence of an association in the reverse direction between depressive symptoms and incident IPV (pooled OR from four studies = 1.93, 95% CI 1.51–2.48, I2 = 0%, p = 0.481). IPV was also associated with incident suicide attempts. For men, evidence suggested that IPV was associated with incident depressive symptoms, but there was no clear evidence of an association between IPV and suicide attempts or depression and incident IPV.
Conclusions
In women, IPV was associated with incident depressive symptoms, and depressive symptoms with incident IPV. IPV was associated with incident suicide attempts. In men, few studies were conducted, but evidence suggested IPV was associated with incident depressive symptoms. There was no clear evidence of association with suicide attempts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depression and suicide are responsible for a substantial proportion of the global disease burden. Depression—an overwhelming feeling of sadness and hopelessness that can last for months or years—affects more than 350 million people worldwide. It is the eleventh leading cause of global disability-adjusted life-years (a measure of overall disease burden), and it affects one in six people at some time during their lives. Globally, about a million people commit suicide every year, usually because they have depression or some other mental illness. Notably, in cross-sectional studies (investigations that look at a population at a single time point), experience of intimate partner violence (IPV, also called domestic violence) is strongly and consistently associated with both depressive disorders and suicide. IPV, like depression and suicide, is extremely common—in multi-country studies, 15%–71% of women report being physically assaulted at some time during their lifetime. IPV is defined as physical, sexual, or psychological harm by a current or former partner or spouse; men as well as women can be the victims of IPV.
Why Was This Study Done?
It may seem obvious to assume that IPV is causally related to subsequent depression and suicidal behavior. However, cross-sectional studies provide no information about causality, and it is possible that depression and/or suicide attempts cause subsequent IPV or that there are common risk factors for IPV, depression, and suicide. For example, individuals with depressive symptoms may be more accepting of partners with characteristics that predispose them to use violence, or early life exposure to violence may predispose individuals to both depression and choosing violent partners. Here, as part of the Global Burden of Disease Study 2010, the researchers investigate the extent to which experience of IPV is associated with subsequent depression and suicide attempts and vice versa in both men and women by undertaking a systematic review and meta-analysis of longitudinal studies that have examined IPV, depression, and suicide attempts. A systematic review uses predefined criteria to identify all the research on a given topic, meta-analysis combines the results of several studies, and longitudinal studies track people over time to investigate associations between specific characteristics and outcomes.
What Did the Researchers Do and Find?
The researchers identified 16 longitudinal studies involving a total of 36,163 participants that met their inclusion criteria. All the studies included women, but only four also included men. All the studies were undertaken in high- and middle-income countries. For women, 11 studies showed a statistically significant association (an association unlikely to have occurred by chance) between IPV and subsequent depressive symptoms. In a meta-analysis of six studies, experience of IPV nearly doubled the risk of women subsequently reporting depressive symptoms. In addition, there was evidence of an association in the reverse direction. In a meta-analysis of four studies, depressive symptoms nearly doubled the risk of women subsequently experiencing IPV. IPV was also associated with subsequent suicide attempts among women. For men, there was some evidence from two studies that IPV was associated with depressive symptoms but no evidence for an association between IPV and subsequent suicide attempt or between depressive symptoms and subsequent IPV.
What Do These Findings Mean?
These findings suggest that women who are exposed to IPV are at increased risk of subsequent depression and that women who are depressed are more likely to be at risk of IPV. They also provide evidence of an association between IPV and subsequent suicide attempt for women. The study provides little evidence for similar relationships among men, but additional studies are needed to confirm this finding. Moreover, the accuracy of these findings is likely to be affected by several limitations of the study. For example, few of the included studies controlled for other factors that might have affected both exposure to IPV and depressive symptoms, and none of the studies considered the effect of emotional violence on depressive symptoms and suicide attempts. Nevertheless, these findings have two important implications. First, they suggest that preventing violence against women has the potential to reduce the global burden of disease related to depression and suicide. Second, they suggest that clinicians should pay attention to past experiences of violence and the risk of future violence when treating women who present with symptoms of depression.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001439.
This study is further discussed in a PLOS Medicine Perspective by Alexander Tsai
The US National Institute of Mental Health provides information on all aspects of depression and of suicide and suicide prevention (in English and Spanish)
The UK National Health Service Choices website provides detailed information about depression, including personal stories about depression, and information on suicide and its prevention; it has a webpage about domestic violence, which includes descriptions of personal experiences
The World Health Organization provides information on depression, on the global burden of suicide and on suicide prevention, and on intimate partner violence (some information in several languages)
MedlinePlus provides links to other resources about depression, suicide, and domestic violence (in English and Spanish)
The charity Healthtalkonline has personal stories about depression and about dealing with suicide
doi:10.1371/journal.pmed.1001439
PMCID: PMC3646718  PMID: 23671407
9.  Duration of Lactation and Incidence of the Metabolic Syndrome in Women of Reproductive Age According to Gestational Diabetes Mellitus Status: A 20-Year Prospective Study in CARDIA (Coronary Artery Risk Development in Young Adults) 
Diabetes  2009;59(2):495-504.
OBJECTIVE
The objective of the study was to prospectively assess the association between lactation duration and incidence of the metabolic syndrome among women of reproductive age.
RESEARCH DESIGN AND METHODS
Participants were 1,399 women (39% black, aged 18–30 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an ongoing multicenter, population-based, prospective observational cohort study conducted in the U.S. Women were nulliparous and free of the metabolic syndrome at baseline (1985–1986) and before subsequent pregnancies, and reexamined 7, 10, 15, and/or 20 years after baseline. Incident metabolic syndrome case participants were identified according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Complementary log-log models estimated relative hazards of incident metabolic syndrome among time-dependent lactation duration categories by gestational diabetes mellitus (GDM) adjusted for age, race, study center, baseline covariates (BMI, metabolic syndrome components, education, smoking, physical activity), and time-dependent parity.
RESULTS
Among 704 parous women (620 non-GDM, 84 GDM), there were 120 incident metabolic syndrome case participants in 9,993 person-years (overall incidence rate 12.0 per 1,000 person-years; 10.8 for non-GDM, 22.1 for GDM). Increased lactation duration was associated with lower crude metabolic syndrome incidence rates from 0–1 month through >9 months (P < 0.001). Fully adjusted relative hazards showed that risk reductions associated with longer lactation were stronger among GDM (relative hazard range 0.14–0.56; P = 0.03) than non-GDM groups (relative hazard range 0.44–0.61; P = 0.03).
CONCLUSIONS
Longer duration of lactation was associated with lower incidence of the metabolic syndrome years after weaning among women with a history of GDM and without GDM, controlling for preconception measurements, BMI, and sociodemographic and lifestyle traits. Lactation may have persistent favorable effects on women's cardiometabolic health.
doi:10.2337/db09-1197
PMCID: PMC2809964  PMID: 19959762
10.  Depressive Symptom Dimensions and Cardiovascular Prognosis among Women with Suspected Myocardial Ischemia: A Report from the NHLBI-Sponsored WISE Study 
Archives of general psychiatry  2009;66(5):499-507.
Context:
Symptoms of depression and cardiovascular disease overlap substantially. Differentiating between dimensions of depressive symptoms may improve our understanding of the relationship between depression and physical health.
Objective:
To compare symptom dimensions of depression as predictors of cardiovascular-related death and events among women with suspected myocardial ischemia.
Design:
Cohort study of women with suspected myocardial ischemia who were evaluated at baseline for history of cardiovascular-related problems, depressive symptoms using the Beck Depression Inventory (BDI), and coronary artery disease severity via coronary angiogram. Principal components analyses (PCA) of the BDI items were conducted to examine differential cardiovascular prognosis according to symptom dimensions of depression.
Setting:
The Women's Ischemia Syndrome Evaluation (WISE), a National Heart, Lung, and Blood Institute (NHLBI)–sponsored multi-center study assessing cardiovascular function using state-of-the-art techniques in women referred for coronary angiography to evaluate chest pain or suspected myocardial ischemia.
Participants:
550 women (mean age = 58.4 [11.2] years) enrolled in WISE and followed for a median of 5.8 years.
Main Outcome Measures:
Cardiovascular-related mortality and events (stroke, myocardial infarction, and congestive heart failure).
Results:
Using a three-factor structure from PCA, somatic/affective (hazards ratio [HR]=1.35, 95% confidence interval [CI]=1.04-1.74) and appetitive (HR=1.42, 95%CI=1.21-1.68) but not cognitive/affective (HR=.89, 95%CI=.70-1.14) symptoms predicted cardiovascular prognosis in adjusted multivariate Cox regression analysis. Using a two-factor structure from PCA, adjusted results indicated that somatic (HR=1.63, 95% CI=1.28-2.08) but not cognitive/affective (HR=.87, 95% CI=.68-1.11) symptoms predicted worse prognosis.
Conclusions:
In a sample of women with suspected myocardial ischemia, somatic but not cognitive/affective depressive symptoms were associated with an increased risk of cardiovascular-related mortality and events. These results support the need to research dimensions of depression in CVD populations and have implications for understanding the connection between depression and CVD.
Unstructured Abstract
Differentiating between dimensions of depressive symptoms may improve our understanding of the relationship between depression and cardiovascular disease (CVD). This study examined depressive symptom dimensions as predictors of cardiovascular-related death and events among women undergoing coronary angiography to evaluate suspected myocardial ischemia (n=550; mean age=58.4 [11.2] years). Baseline evaluation included depressive symptom assessment using the Beck Depression Inventory (BDI) and coronary artery disease severity testing via coronary angiogram. Incidence of the women's cardiovascular-related mortality and events (stroke, myocardial infarction, and congestive heart failure) was tracked for a median of 5.8 years. Principal components analyses (PCA) of the 21 BDI items were conducted to derive depression symptom dimensions. Using a three-factor structure, somatic/affective (HR=1.35, 95%CI=1.04-1.74) and appetitive (HR=1.42, 95%CI=1.21-1.68) but not cognitive/affective (HR=.89, 95%CI=.70-1.14) symptoms predicted cardiovascular prognosis in adjusted multivariate Cox regression analysis. Using a two-factor structure, adjusted results indicated that somatic (HR=1.63, 95% CI=1.28-2.08) but not cognitive/affective (HR=.87, 95% CI=.68-1.11) symptoms predicted prognosis. Thus, in a sample of women with suspected myocardial ischemia, somatic but not cognitive/affective depressive symptoms were associated with worse cardiovascular prognosis. These results support the need to research depressive symptom dimensions in CVD populations and have implications for understanding the connection between depression and CVD.
doi:10.1001/archgenpsychiatry.2009.27
PMCID: PMC2697960  PMID: 19414709
11.  Depressive Symptoms and the Metabolic Syndrome in Childhood and Adulthood 
Objective
To examine the reciprocal associations between depressive symptoms and clinical definitions of the metabolic syndrome in childhood and adulthood.
Design
Population-based prospective cohort study of 921 participants (538 women and 383 men) in Finland. The components of the metabolic syndrome were measured in childhood (mean age 12 years) and again in adulthood (mean age 33 years). A revised version of the Beck Depression Inventory was used to assess depressive symptoms at the mean ages of 24 and 33.
Main Outcome Measures
Metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), the European Group for the Study of Insulin Resistance, and the International Diabetes Federation criteria.
Results
In women, depressive symptoms were associated with increased risk of the metabolic syndrome in adulthood (odds ratio for NCEP metabolic syndrome per 1 SD increase in depressive symptoms 1.40, 95% confidence interval 1.05-1.85). The metabolic syndrome in childhood, in turn, predicted higher levels of depressive symptoms in adulthood (p= 0.03). In men, no associations were found between depressive symptoms and the clinical definitions of the metabolic syndrome.
Conclusion
The process linking depressive symptoms with the metabolic syndrome may go into both directions and may begin early in life.
doi:10.1037/a0012646
PMCID: PMC3166561  PMID: 19210024
metabolic syndrome; depressive symptoms; obesity; cardiovascular disease; childhood
12.  Prospective Study of Serum Adiponectin and Incident Metabolic Syndrome 
Diabetes Care  2013;36(6):1547-1553.
OBJECTIVE
Increased adiponectin levels may play a protective role in the development of metabolic abnormalities, but prospective studies of the predictive value of serum adiponectin to identify individuals at high risk of new-onset metabolic syndrome are lacking. We investigated whether serum adiponectin predicts incident cases of the metabolic syndrome in a population-based longitudinal study.
RESEARCH DESIGN AND METHODS
A prospective cohort study was conducted of 2,044 adults (831 men and 1,213 women) aged 40–70 years without metabolic syndrome examined in 2005–2008 (baseline) and 2008–2011 (follow-up). Baseline serum adiponectin concentrations were measured by radioimmunoassay.
RESULTS
During an average of 2.6 years of follow-up, 153 men (18.4%) and 199 women (16.4%) developed metabolic syndrome. In multivariable-adjusted models, the odds ratio for incident metabolic syndrome comparing the highest with the lowest quartiles of adiponectin levels was 0.25 (95% CI 0.14–0.47) in men and 0.45 (0.28–0.74) in women. While serum adiponectin did not improve the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components, the net reclassification improvement and the integrated discrimination improvement of prediction models including adiponectin were significantly higher compared with those of models not including adiponectin among men, with a significant difference between men and women (P = 0.001).
CONCLUSIONS
Increased adiponectin is an independent protective factor for incident metabolic syndrome in men and women, and it may have a clinical role in predicting new-onset metabolic syndrome among men.
doi:10.2337/dc12-0223
PMCID: PMC3661834  PMID: 23275369
13.  Domestic Violence and Perinatal Mental Disorders: A Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(5):e1001452.
Louise Howard and colleagues conduct a systematic review and meta-analysis to estimate the prevalence and odds of experience of domestic violence experience among women with antenatal and postnatal mental health disorders.
Please see later in the article for the Editors' Summary
Background
Domestic violence in the perinatal period is associated with adverse obstetric outcomes, but evidence is limited on its association with perinatal mental disorders. We aimed to estimate the prevalence and odds of having experienced domestic violence among women with antenatal and postnatal mental disorders (depression and anxiety disorders including post-traumatic stress disorder [PTSD], eating disorders, and psychoses).
Methods and Findings
We conducted a systematic review and meta-analysis (PROSPERO reference CRD42012002048). Data sources included searches of electronic databases (to 15 February 2013), hand searches, citation tracking, update of a review on victimisation and mental disorder, and expert recommendations. Included studies were peer-reviewed experimental or observational studies that reported on women aged 16 y or older, that assessed the prevalence and/or odds of having experienced domestic violence, and that assessed symptoms of perinatal mental disorder using a validated instrument. Two reviewers screened 1,125 full-text papers, extracted data, and independently appraised study quality. Odds ratios were pooled using meta-analysis.
Sixty-seven papers were included. Pooled estimates from longitudinal studies suggest a 3-fold increase in the odds of high levels of depressive symptoms in the postnatal period after having experienced partner violence during pregnancy (odds ratio 3.1, 95% CI 2.7–3.6). Increased odds of having experienced domestic violence among women with high levels of depressive, anxiety, and PTSD symptoms in the antenatal and postnatal periods were consistently reported in cross-sectional studies. No studies were identified on eating disorders or puerperal psychosis. Analyses were limited because of study heterogeneity and lack of data on baseline symptoms, preventing clear findings on causal directionality.
Conclusions
High levels of symptoms of perinatal depression, anxiety, and PTSD are significantly associated with having experienced domestic violence. High-quality evidence is now needed on how maternity and mental health services should address domestic violence and improve health outcomes for women and their infants in the perinatal period.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Domestic violence—physical, sexual, or emotional abuse by an intimate partner or family member—is a major public health problem and although more common in women, can also affect men. Due to the nature of the problem, it is difficult to collect accurate figures on the scale of domestic violence, but a study by the World Health Organization in ten countries found that 15%–71% of women aged 15–49 years reported physical and/or sexual violence by an intimate partner at some point in their lives. Women experiencing domestic violence have significant short- and long-term health problems, particularly regarding their mental health: experience of domestic violence can lead to a range of mental health disorders such as depression, psychosis, eating disorders, and even suicide attempts.
Why Was This Study Done?
As perinatal mental health disorders are among the commonest health problems in pregnancy and the postpartum period, and given the rate of domestic violence during pregnancy (previous studies have suggested a domestic violence prevalence of 4%–8% during pregnancy and the postnatal period), it is plausible that there may be a link between perinatal mental health disorders and having experienced domestic violence. Indeed, previous reviews have suggested the existence of such an association but were limited by the small number of included studies and focused on depression only, rather than the full range of antenatal and postnatal mental health disorders. So in this study the researchers systematically reviewed published studies to provide more robust estimates of the prevalence of having experienced domestic violence among women with antenatal and postnatal mental health disorders; the researchers also used a meta-analysis to estimate the odds (chance) of having experienced domestic violence among women with antenatal and postnatal mental health disorders.
What Did the Researchers Do and Find?
The researchers searched multiple databases and hand searched three relevant journals using key search terms to identify all types of relevant studies. Using specific criteria, the researchers retrieved and assessed over 1,000 full papers, of which 67 met the criteria for their systematic review. The researchers assessed the quality of each selected study and included only those studies that used validated diagnostic instruments and screening tools to assess mental health disorders in their calculations of the pooled (combined) odds ratio (OR) through meta-analysis.
Using these methods, in cross-sectional studies (studies conducted at one point in time), the researchers found that women with probable depression in the antenatal period reported a high prevalence and increased odds of having experienced partner violence during their lifetime (OR = 3), during the past year (OR = 2.8), and during pregnancy (OR = 5). The results were similar for the postnatal period. The evidence was less robust for anxiety disorders: among women with probable anxiety in the antenatal period, the researchers found an OR of 2.9 of having experienced lifetime partner violence. The odds were less in the postnatal period (OR = 1.4) In their analysis of longitudinal studies (follow-up studies over a period of time), the researchers found an increased odds of probable postnatal depression both among women who reported having ever experienced partner violence in their lifetime (OR = 2.9) and among women who reported having experienced partner violence during pregnancy (OR = 3.1). The researchers also found a combined prevalence estimate of 12.7% for probable depression during the postnatal period following experiences of partner violence during pregnancy. Because of limited data, the researchers could not calculate an OR of the association between probable antenatal depression and later experiences of partner violence.
What Do These Findings Mean?
These findings suggest that women with high levels of symptoms of perinatal mental health disorders—antenatal and postnatal anxiety, depression, and post-traumatic stress disorder—have a high prevalence and increased odds of having experienced domestic violence both over their lifetime and during pregnancy. However, these findings cannot prove causality, they fail to show a two-way association (that is, perinatal mental health disorders leading to subsequent domestic violence), and no information on other perinatal mental disorders, such as eating disorders and puerperal psychosis, was available. The variation of the quality of the included studies also limits the results, highlighting the need for high-quality data to suggest how maternity and mental health services could address domestic violence and improve health outcomes for women and their infants in the future. Nevertheless, this study emphasizes the importance of identifying and responding to possible domestic violence among women attending antenatal and mental health services.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001452.
The World Health Organization provides information and statistics about violence against women and also about mental health disorders during pregnancy
The UK Royal College of Psychiatrists has information for professionals and patients about mental health disorders during pregnancy
doi:10.1371/journal.pmed.1001452
PMCID: PMC3665851  PMID: 23723741
14.  Metabolic syndrome and risk of incident diabetes: findings from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study 
Background
Several aspects concerning the relationship between the metabolic syndrome and incident diabetes are incompletely understood including the magnitude of the risk estimate, potential gender differences in the associations between the metabolic syndrome and incident diabetes, the associations between the components of the metabolic syndrome and incident diabetes, and whether the metabolic syndrome provides additional prediction beyond its components. To shed light on these issues, we examined the prospective association between the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) and diabetes.
Methods
We used data for 2796 men and women aged 35–65 years from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study followed for an average of 6.9 years. This analysis employed a case-cohort design that included 697 participants who developed diabetes and 2099 participants who did not. Incident diabetes was identified on the basis of self-reports and verified by contacting the patient's attending physician.
Results
The adjusted hazard ratio for the NCEP definition was 4.62 (95% confidence interval [CI]: 3.90–5.48) and that for the IDF definition was 4.59 (95% CI: 3.84–5.50). The adjusted hazard ratios for the NCEP but not IDF definition were higher for women than men. When participants who had no cardiometabolic abnormalities were used as the reference group for the NCEP definition, the adjusted hazard ratio for having 3 or more abnormalities increased to 22.50 (95% CI: 11.21–45.19). Of the five components, abdominal obesity and hyperglycemia were most strongly associated with incident diabetes.
Conclusion
In this study population, both definitions of the metabolic syndrome provided similar estimates of relative risk for incident diabetes. The increase in risk for participants with the metabolic syndrome according to the NCEP definition was very large when contrasted with the risk among those who had no cardiometabolic abnormalities.
doi:10.1186/1475-2840-7-35
PMCID: PMC2627822  PMID: 19077281
15.  Subthreshold Depressive Disorder in Adolescents: Predictors of Escalation to Full-Syndrome Depressive Disorders 
Objectives
Subthreshold depressive disorder is one of the best established risk factors for the onset of full-syndrome depressive disorders. However, many youths with subthreshold depressive disorder do not develop full-syndrome depression. We examined predictors of escalation to full-syndrome depressive disorders in a community sample of 225 adolescents with subthreshold depressive disorder.
Method
Criteria for subthreshold depressive disorder were an episode of depressed mood or loss of interest or pleasure lasting at least 1 week and at least two of the seven other DSM-IV-associated symptoms for major depression. Participants were assessed four times from mid-adolescence to age 30 years using semistructured diagnostic interviews.
Results
The estimated risk for escalation to full-syndrome depressive disorders was 67%. Five variables accounted for unique variance in predicting escalation: severity of depressive symptoms, medical conditions/symptoms, history of suicidal ideation, history of anxiety disorder, and familial loading for depression. Adolescents with three or more risk factors had an estimated 90% chance of escalating to full-syndrome depressive disorder, compared with 47% of adolescents with fewer than three risk factors.
Conclusions
These data may be useful in identifying a subgroup of youths with subthreshold depressive disorder who are at especially high risk for escalating to full-syndrome depressive disorders.
doi:10.1097/CHI.0b013e3181a56606
PMCID: PMC2866498  PMID: 19465876
16.  Burden of Depressive Disorders by Country, Sex, Age, and Year: Findings from the Global Burden of Disease Study 2010 
PLoS Medicine  2013;10(11):e1001547.
In this paper, Ferrari and colleagues analyzed the burden of depressive disorders in GBD 2010 and identified depressive disorders as a leading cause of burden. The authors present severity proportions; burden by country, region, age, sex, and year; as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Please see later in the article for the Editors' Summary
Background
Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Methods and Findings
Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders.
Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%–10.8%) of global YLDs and dysthymia for 1.4% (0.9%–2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%–3.2%) of global DALYs and dysthymia for 0.5% (0.3%–0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%–3.8%) to 3.8% (3.0%–4.7%) of global DALYs.
Conclusions
GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depressive disorders are common mental disorders that occur in people of all ages across all world regions. Depression—an overwhelming feeling of sadness and hopelessness that can last for months or years—can make people feel that life is no longer worth living. People affected by depression lose interest in the activities they used to enjoy and can also be affected by physical symptoms such as disturbed sleep. Major depressive disorder (MDD, also known as clinical depression) is an episodic disorder with a chronic (long-term) outcome and increased risk of death. It involves at least one major depressive episode in which the affected individual experiences a depressed mood almost all day, every day for at least 2 weeks. Dysthymia is a milder, chronic form of depression that lasts for at least 2 years. People with dysthymia are often described as constantly unhappy. Both these subtypes of depression (and others such as that experienced in bipolar disorder) can be treated with antidepressant drugs and with talking therapies.
Why Was This Study Done?
Depressive disorders were a leading cause of disease burden in the 1990 and 2000 Global Burden of Disease (GBD) studies, collaborative scientific efforts that quantify the health loss attributable to diseases and injuries in terms of disability adjusted life years (DALYs; one DALY represents the loss of a healthy year of life). DALYs are calculated by adding together the years of life lived with a disability (YLD, a measure that includes a disability weight factor reflecting disease severity) and the years of life lost because of disorder-specific premature death. The GBD initiative aims to provide data that can be used to improve public-health policy. Thus, knowing that depressive disorders are a leading cause of disease burden worldwide has helped to prioritize depressive disorders in global public-health agendas. Here, the researchers analyze the burden of MDD and dysthymia in GBD 2010 by country, region, age, and sex, and calculate the burden of suicide and ischemic heart disease attributable to depressive disorders (depression is a risk factor for suicide and ischemic heart disease). GBD 2010 is broader in scope than previous GBD studies and quantifies the direct burden of 291 diseases and injuries and the burden attributable to 67 risk factors across 187 countries.
What Did the Researchers Do and Find?
The researchers collected data on the prevalence, incidence, remission rates, and duration of MDD and dysthymia and on the excess deaths caused by these disorders from published articles. They pooled these data using a statistical method called Bayesian meta-regression and calculated YLDs for MDD and dysthymia using disability weights collected in population surveys. MDD accounted for 8.2% of global YLDs in 2010, making it the second leading cause of YLDs. Dysthymia accounted for 1.4% of global YLDs. MDD and dysthymia were also leading causes of DALYs, accounting for 2.5% and 0.5% of global DALYs, respectively. The regional variation in the burden was greater for MDD than for dysthymia, the burden of depressive disorders was higher in women than men, the largest proportion of YLDs from depressive disorders occurred among adults of working age, and the global burden of depressive disorders increased by 37.5% between 1990 and 2010 because of population growth and ageing. Finally, MDD explained an additional 16 million DALYs and 4 million DALYs when it was considered as a risk factor for suicide and ischemic heart disease, respectively. This “attributable” burden increased the overall burden of depressive disorders to 3.8% of global DALYs.
What Do These Findings Mean?
These findings update and extend the information available from GBD 1990 and 2000 on the global burden of depressive disorders. They confirm that depressive disorders are a leading direct cause of the global disease burden and show that MDD also contributes to the burden allocated to suicide and ischemic heart disease. The estimates of the global burden of depressive disorders reported in GBD 2010 are likely to be more accurate than those in previous GBD studies but are limited by factors such as the sparseness of data on depressive disorders from developing countries and the validity of the disability weights used to calculate YLDs. Even so, these findings reinforce the importance of treating depressive disorders as a public-health priority and of implementing cost-effective interventions to reduce their ubiquitous burden.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001547.
The US National Institute of Mental Health provides information on all aspects of depression
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
More personal stories about depression are available from healthtalkonline.org
MedlinePlus provides links to other resources about depression (in English and Spanish)
The World Health Organization provides information on depression and on the global burden of disease (in several languages)
Information about the Global Burden of Disease initiative is available
beyondblue provides many resources on depression
The Queensland Centre for Mental Health Research provides information on epidemiology and the global burden of disease specifically for mental disorders
doi:10.1371/journal.pmed.1001547
PMCID: PMC3818162  PMID: 24223526
17.  Increased Plasma DPP4 Activity Is an Independent Predictor of the Onset of Metabolic Syndrome in Chinese over 4 Years: Result from the China National Diabetes and Metabolic Disorders Study 
PLoS ONE  2014;9(3):e92222.
Aims
To determine whether fasting plasma Dipeptidyl Peptidase 4 (DPP4) activity and active Glucagon-Like Peptide-1 (GLP-1) were predictive of the onset of metabolic syndrome.
Methods
A prospective cohort study was conducted of 2042 adults (863 men and 1,179 women) aged 18-70 years without metabolic syndrome examined in 2007(baseline) and 2011(follow-up). Baseline plasma DPP4 activity was determined as the rate of cleavage of 7-amino-4- methylcoumarin (AMC) from the synthetic substrate H-glycyl-prolyl-AMC and active GLP-1 was determined by enzymoimmunoassay.
Results
During an average of 4 years of follow-up, 131 men (15.2%) and 174 women (14.8%) developed metabolic syndrome. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in insulin resistance over a 4-year period (P<0.01). In multivariable-adjusted models, the odds ratio (OR) for incident metabolic syndrome comparing the highest with the lowest quartiles of DPP4 activity and active GLP-1 were 2.82, 0.45 for men and 2.48, 0.36 for women respectively. Furthermore, plasma DPP4 activity significantly improved the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components (Both P<0.01).
Conclusions
DPP4 activity is an important predictor of the onset of insulin resistance and metabolic syndrome in apparently healthy Chinese men and women. This finding may have important implications for understanding the aetiology of metabolic syndrome.
Trial Registration
#TR-CCH-Chi CTR-CCH-00000361
doi:10.1371/journal.pone.0092222
PMCID: PMC3960228  PMID: 24647445
18.  Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women 
PLoS Medicine  2011;8(12):e1001141.
An Pan and colleagues examined data from two Nurses' Health Studies and found that extended periods of rotating night shift work were associated with a modestly increased risk of type 2 diabetes, partly mediated through body weight.
Background
Rotating night shift work disrupts circadian rhythms and has been associated with obesity, metabolic syndrome, and glucose dysregulation. However, its association with type 2 diabetes remains unclear. Therefore, we aimed to evaluate this association in two cohorts of US women.
Methods and Findings
We followed 69,269 women aged 42–67 in Nurses' Health Study I (NHS I, 1988–2008), and 107,915 women aged 25–42 in NHS II (1989–2007) without diabetes, cardiovascular disease, and cancer at baseline. Participants were asked how long they had worked rotating night shifts (defined as at least three nights/month in addition to days and evenings in that month) at baseline. This information was updated every 2–4 years in NHS II. Self-reported type 2 diabetes was confirmed by a validated supplementary questionnaire. We documented 6,165 (NHS I) and 3,961 (NHS II) incident type 2 diabetes cases during the 18–20 years of follow-up. In the Cox proportional models adjusted for diabetes risk factors, duration of shift work was monotonically associated with an increased risk of type 2 diabetes in both cohorts. Compared with women who reported no shift work, the pooled hazard ratios (95% confidence intervals) for participants with 1–2, 3–9, 10–19, and ≥20 years of shift work were 1.05 (1.00–1.11), 1.20 (1.14–1.26), 1.40 (1.30–1.51), and 1.58 (1.43–1.74, p-value for trend <0.001), respectively. Further adjustment for updated body mass index attenuated the association, and the pooled hazard ratios were 1.03 (0.98–1.08), 1.06 (1.01–1.11), 1.10 (1.02–1.18), and 1.24 (1.13–1.37, p-value for trend <0.001).
Conclusions
Our results suggest that an extended period of rotating night shift work is associated with a modestly increased risk of type 2 diabetes in women, which appears to be partly mediated through body weight. Proper screening and intervention strategies in rotating night shift workers are needed for prevention of diabetes.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Around 346 million people worldwide have diabetes—a chronic disease affecting blood glucose levels, which over time may lead to serious damage in many body systems. In 2004, an estimated 3.4 million people died from consequences of high blood sugar, with more than 80% of deaths occurring in low-and middle-income countries. Type 2 diabetes accounts for 90% of people with diabetes and is largely the result of excess body weight and physical inactivity, which causes the body to use insulin ineffectively. One strategy in the public health response to the increasing prevalence and incidence of type 2 diabetes is to focus on the prevention and management of obesity by targeting risk factors of obesity.
Previous studies have suggested that rotating night shift work, which is common and becoming increasingly prevalent in countries worldwide, is associated with an increased risk of obesity and metabolic syndrome, conditions closely related to type 2 diabetes.
Why Was This Study Done?
Some studies have investigated the association between rotating night shift work and type 2 diabetes but have experienced methodological problems (such as minimal information on the rotating shift work, small sample sizes, and limited study populations), which make interpretation of the results difficult. In this study, the researchers attempted to overcome these methodological issues by prospectively examining the relationship between duration of rotating night shift work and risk of incident type 2 diabetes and, also if the duration of shift work was associated with greater weight gain, in two large cohorts of women in the United States.
What Did the Researchers Do and Find?
The researchers used data from the Nurses' Health Study I (NHS I, established in 1976 and included 121,704 women) and the Nurses' Health Study II (NHS II, established in 1989 and included 116,677 women), in which participating women completed regular questionnaires about their lifestyle practices and the development of chronic diseases. In both studies, the women also gave information about how long they had done rotating night shifts work (defined as at least three nights/month in addition to 19 days and evenings in that month), and this information was updated at regular intervals over the study follow-up period (18 years). The comparison group was women who did not report a history of rotating night shift work.
To assess the incidence of diabetes in both cohorts, the researchers sent a supplementary questionnaire to women who reported a diagnosis of diabetes, which asked about the symptoms, diagnostic tests, and medical management: if at least one of the National Diabetes Data Group criteria was reported, the researchers considered confirmed a diagnosis of type 2 diabetes. The researchers then used statistical methods (time-dependent Cox proportional hazards models) to estimate the hazard ratios of the chance of women working rotating shifts developing type 2 diabetes as a ratio of the chance of women not working rotating shifts developing diabetes.
The researchers found that in NHS I, 6,165 women developed type 2 diabetes and in NHS II 3,961 women developed type 2 diabetes. Using their statistical models, the researchers found that the duration of rotating night shift work was strongly associated with an increased risk of type 2 diabetes in both cohorts. The researchers found that in both cohorts, compared with women who reported no rotating night shift work, the HR of women developing type 2 diabetes, increased with the numbers of years working rotating shifts (the HRs of working rotating shifts for 1–2, 3–9, 10–19, and ≥20 years were 0.99, 1.17, 1.42, and 1.64, respectively, in NHS I, and in NHS II, 1.13, 1.34, 1.76, and 2.50, respectively). However, these associations were slightly weaker after the authors took other factors into consideration, except for body mass index (BMI).
What Do These Findings Mean?
These findings show that in these women, there is a positive association between rotating night shift work and the risk of developing type 2 diabetes. Furthermore, long duration of shift work may also be associated with greater weight gain. Although these findings need to be confirmed in men and other ethnic groups, because a large proportion of the working population is involved in some kind of permanent night and rotating night shift work, these findings are of potential public health significance. Additional preventative strategies in rotating night shift workers should therefore be considered.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001141.
This study is further discussed in a PLoS Medicine Perspective by Mika Kivimki and colleagues
Wikipedia has information about the Nurses’ Health study (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Detailed information about the Nurses’ Health Study is available
The World Health Organization provides comprehensive information about all kinds of diabetes
For more information about diabetes that is useful for patients see Diabetes UK
doi:10.1371/journal.pmed.1001141
PMCID: PMC3232220  PMID: 22162955
19.  Predictors of the Onset of Manic Symptoms and a (Hypo)Manic Episode in Patients with Major Depressive Disorder 
PLoS ONE  2014;9(9):e106871.
Objective
One third of patients with a major depressive episode also experience manic symptoms or, even, a (hypo)manic episode. Retrospective studies on the temporal sequencing of symptomatology suggest that the majority of these patients report depressive symptoms before the onset of manic symptoms. However, prospective studies are scarce and this study will, therefore, prospectively examine the onset of either manic symptoms or a (hypo)manic episode in patients with a major depressive disorder. In addition, we will consider the impact of a large set of potential risk factors on both outcomes.
Methodology
Four-year follow-up data were used to determine the onset of manic symptoms as well as a CIDI-based (hypo)manic episode in a large sample (n = 889, age: 18–65 years) of outpatients with a major depressive disorder and without manic symptoms at baseline. Baseline vulnerability (i.e., sociodemographics, family history of depression, childhood trauma, life-events) and clinical (i.e., isolated manic symptoms, depression characteristics, and psychiatric comorbidity) factors were considered as potential risk factors.
Results
In our sample of depressed patients, 15.9% developed manic symptoms and an additional 4.7% developed a (hypo)manic episode during four years. Baseline isolated manic symptoms and comorbid alcohol dependence predicted both the onset of manic symptoms and a (hypo)manic episode. Low education only predicted the onset of manic symptoms, whereas male gender, childhood trauma and severity of depressive symptoms showed strong associations with, especially, the onset of (hypo)manic episodes.
Conclusions
A substantial proportion (20.6%) of patients with a major depressive disorder later developed manic symptoms or a (hypo)manic episode. Interestingly, some identified risk factors differed for the two outcomes, which may indicate that pathways leading to the onset of manic symptoms or a (hypo)manic episode might be different. Our findings indirectly support a clinical staging model.
doi:10.1371/journal.pone.0106871
PMCID: PMC4178019  PMID: 25259889
20.  Obesity and the three-year longitudinal course of bipolar disorder 
Bipolar disorders  2013;15(3):284-293.
Objectives
Despite substantial cross-sectional evidence that obesity is associated with increased medical and psychiatric burden in bipolar disorder (BD), few longitudinal studies have examined this topic.
Methods
Subjects with BD (n = 1,600) who completed both Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were included. Analyses examined the association between obesity at Wave 1, and the subsequent course of BD, and of psychiatric and medical comorbidities, between Wave 1 and Wave 2.
Results
BD subjects with obesity (n = 506; 29.43%), compared to BD subjects without obesity (n = 1,094; 70.57%) were significantly more likely to have a major depressive episode and to receive counseling for depression during follow-up, more likely to report a lifetime suicide attempt, and less likely to develop new onset alcohol use disorders. These differences were no longer significant, however, after controlling for baseline demographic variables. No significant differences in new episodes or treatment of mania/hypomania were observed. After controlling for demographic variables, obese subjects remained significantly more likely to report any new-onset medical condition [odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.63–3.30], and new-onset hypertension (OR = 1.81, 95% CI: 1.16–2.82) and arthritis (OR = 1.64, 95% CI: 1.07–2.52). Obese subjects were significantly more likely to report physician-diagnosed diabetes (OR = 6.98, 95% CI: 4.27–11.40) and hyperlipidemia (OR = 2.32, 95% CI: 1.63–3.30) (assessed in Wave 2 only). The incidence of heart attacks was doubled among obese subjects, although this difference was not statistically significant.
Conclusions
The association between obesity and increased prospective depressive burden appears to be explained by baseline demographic variables. In contrast, obesity independently predicts the accumulation of medical conditions among adults with BD. Treatment of obesity could potentially mitigate the psychiatric and medical burden of BD.
doi:10.1111/bdi.12035
PMCID: PMC3620842  PMID: 23286532
bipolar disorder; epidemiologic; longitudinal; obesity
21.  Metabolic Syndrome and Risk of Development of Atrial Fibrillation 
Circulation  2008;117(10):1255-1260.
Background
The metabolic syndrome consists of a cluster of atherosclerotic risk factors, many of which also have been implicated in the genesis of atrial fibrillation (AF). However, the precise role of the metabolic syndrome in the development of AF is unknown.
Methods and Results
This prospective, community-based, observational cohort study was based on an annual health check-up program in Japan. We studied 28 449 participants without baseline AF. We used 2 different criteria for the metabolic syndrome—the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) and those of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)—to study the risk of development of new-onset AF. The metabolic syndrome was present in 3716 subjects (13%) and 4544 subjects (16%) using the NCEP-ATP III and AHA/NHLBI definitions, respectively. During a mean follow-up of 4.5 years, AF developed in 265 subjects (105 women). Among the metabolic syndrome components, obesity (age- and sex-adjusted hazard ratio [HR], 1.64), elevated blood pressure (HR, 1.69), low high-density lipoprotein cholesterol (HR, 1.52), and impaired insulin tolerance (HR, 1.44 [NCEP-ATP III] and 1.35 [AHA/NHLBI]) showed an increased risk for AF. The association between the metabolic syndrome and AF remained significant in subjects without treated hypertension or diabetes by the NCEP-ATP III definition (HR, 1.78) but not by the AHA/NHLBI definition (HR, 1.28).
Conclusions
The metabolic syndrome was associated with increased risk of AF. The metabolic derangements of the syndrome may be important in the pathogenesis of AF.
doi:10.1161/CIRCULATIONAHA.107.744466
PMCID: PMC2637133  PMID: 18285562
arrhythmia; diabetes mellitus; hypercholesterolemia; hypertension; metabolic syndrome X; risk factors; obesity
22.  Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes 
PLoS Medicine  2013;10(3):e1001403.
In a systematic review and meta-analysis, Glen Spielmans and colleagues find that adjunctive atypical antipsychotic medications are associated with small-to-moderate improvements in depressive symptoms in patients with depression, but there is little evidence for improvement on measures of quality of life, and these medications are linked to adverse events such as weight gain.
Background
Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk–benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression.
Methods and Findings
We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48–2.73), OFC (OR, 1.42; 95% CI, 1.01–2.0), quetiapine (OR, 1.79; 95% CI, 1.33–2.42), and risperidone (OR, 2.37; 95% CI, 1.31–4.30).
The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58–2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87–1.93), quetiapine (OR, 1.53, 95% CI, 1.17–2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16–2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery–Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49).
Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events.
Conclusions
Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Everyone feels miserable occasionally. But for people who are clinically depressed, feelings of sadness and hopelessness and physical symptoms such as sleeping badly can last for months or years and can make them feel life is no longer worth living. Depression affects one in six people at some time during their life. Clinicians diagnose depression by asking their patients a series of questions about their feelings and symptoms. The answer to each question is given a score, and the total score from the questionnaire (“depression rating scale”) indicates the severity of depression. Treatment of depression often involves talking treatments (psychotherapy) such as cognitive behavioral therapy, which helps people change negative ways of thinking and behaving and antidepressant drugs, most commonly “selective serotonin reuptake inhibitors” such as fluoxetine and paroxetine.
Why Was This Study Done?
Atypical antipsychotic medications (for example, aripiprazole, olanzapine/fluoxetine combination [OFC], quetiapine, and risperidone) are also widely prescribed for the treatment of depression. These drugs, which were developed to treat mental illnesses that are characterized by a loss of contact with reality, are used as adjunctive therapy for depression. That is, they are used in addition to antidepressant drugs. Clinicians wrote nearly four million prescriptions for adjunctive treatment of depression with atypical antipsychotic medications in 2007–2008 in the US alone. However, it is not known whether the benefits of using these drugs to treat depression outweigh their side effects, which include weight gain, sedation, and akathisia (a feeling of inner restlessness resulting in an urge to move, which may or may not be accompanied by increased movement). Here, the researchers undertake a systematic review and meta-analysis of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis is a statistical approach that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 14 short-term randomized controlled trials (duration 4–12 weeks) that compared adjunctive antipsychotic medications (aripiprazole, OFC, quetiapine, or risperidone) to placebo (dummy drug) in the treatment of depression that had not responded to antidepressant medication alone. All four drugs had statistically significant effects (effects unlikely to have happened by chance) on remission, which was most commonly defined as a score of less than eight at the study end point on the Montgomery–Asberg Depression Rating Scale. The researchers calculated the number of patients that would have to be treated for one patient to achieve remission (number needed to treat, or NNT). For OFC, the NNT was 19; for all the other drugs it was nine. All the drugs except OFC also significantly improved response rates (defined as a 50% improvement in depression rating score). However, the medications provided little or no benefit in terms of functioning and quality of life, except for risperidone, which had a small-to-moderate effect on quality of life. Finally, treatment with atypical antipsychotic medications was linked to several adverse effects, including weight gain (all four drugs) and akathisia (aripiprazole).
What Do These Findings Mean?
These results suggest that atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms. However, clinicians should interpret this conclusion cautiously for several reasons. First, adjunctive treatment with atypical antipsychotics provided only small-to-moderate benefits. Moreover, shortcomings in study design and data reporting methods may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events. Second, this study provides little evidence that adjunctive treatment with atypical antipsychotics improves patients' quality of life or reduces their functional impairment. Finally, this study highlights abundant evidence of potential treatment-related harm. This evaluation of the safety and efficacy of adjunctive treatments for clinical depression provides critical insights that should help clinicians better understand the risk–benefit profiles of this approach to the treatment of major depressive disorder.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001403.
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish); it has a webpage on mental health medications that includes information about atypical antipsychotics
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
More personal stories about depression are available from healthtalkonline.org
The UK charity Mind provides information on depression and on antipsychotic drugs; Mind also includes personal stories about depression on its website
MedlinePlus provides links to other resources about depression (in English and Spanish)
Healthy Skepticism is an international nonprofit membership association that aims to improve health by reducing harm from misleading health information
doi:10.1371/journal.pmed.1001403
PMCID: PMC3595214  PMID: 23554581
23.  Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults 
The relation between serum uric acid and metabolic syndrome is observed not only with frank hyperuricemia but also with serum uric acid levels within the normal range. The current “normal” range set for hyperuricemia often fails to identify patients with potential metabolic disorders. We investigate the association between serum uric acid within the normal range and incident metabolic syndrome risk, and further to determine the optimal cut-off value of serum uric acid for the diagnosis or prediction of metabolic syndrome. A total of 7399 Chinese adults (2957 men and 4442 women; ≥20 years) free of metabolic syndrome were followed for 3 years. During the 3-year follow-up, 1190 normouricemic individuals developed metabolic syndrome (16.1%). After adjusting the associated variables, the top quartile of serum uric acid levels was associated with higher metabolic syndrome development compared with the bottom quartile in men (hazard ratio (HR), 1.29; p<0.05) and women (HR, 1.62; p<0.05). ROC curve analysis indicated that the optimal cut-off values for serum uric acid to identify metabolic syndrome were 6.3 mg/dl in men and 4.9 mg/dl in women. Our results suggested that high baseline serum uric acid levels within the normal range predict future development of metabolic syndrome after 3 y of follow-up.
doi:10.3164/jcbn.12-65
PMCID: PMC3541417  PMID: 23341696
serum uric acid; cutoff value; metabolic syndrome; follow-up
24.  Independent Associations of Fasting Insulin, Glucose, and Glycated Haemoglobin with Stroke and Coronary Heart Disease in Older Women 
PLoS Medicine  2007;4(8):e263.
Background
Evidence suggests that variations in fasting glucose and insulin amongst those without frank type 2 diabetes mellitus are important determinants of cardiovascular disease. However, the relative importance of variations in fasting insulin, glucose, and glycated haemoglobin as risk factors for cardiovascular disease in women without diabetes is unclear. Our aim was to determine the independent associations of fasting insulin, glucose, and glycated haemoglobin with coronary heart disease and stroke in older women.
Methods and Findings
We undertook a prospective cohort study of 3,246 British women aged 60–79 y, all of whom were free of baseline coronary heart disease, stroke, and diabetes, and all of whom had fasting glucose levels below 7 mmol/l. Fasting insulin and homeostasis model assessment for insulin sensitivity (HOMA-S) were linearly associated with a combined outcome of coronary heart disease or stroke (n = 219 events), but there was no association of fasting glucose or glycated haemoglobin with these outcomes. Results were similar for coronary heart disease and stroke as separate outcomes. The age, life-course socioeconomic position, smoking, and physical activity adjusted hazard ratio for a combined outcome of incident coronary heart disease or stroke per one standard deviation of fasting insulin was 1.14 (95% CI 1.02–1.33). Additional adjustment for other components of metabolic syndrome, low-density lipoprotein cholesterol, fasting glucose, and glycated haemoglobin had little effect on this result.
Conclusions
Our findings suggest that in women in the 60–79 y age range, insulin resistance, rather than insulin secretion or chronic hyperglycaemia, is a more important risk factor for coronary heart disease and stroke. Below currently used thresholds of fasting glucose for defining diabetes, neither fasting glucose nor glycated haemoglobin are associated with cardiovascular disease.
From a prospective study of women aged 60-79 years, Debbie Lawlor and colleagues conclude that insulin resistance is an important risk factor for coronary heart disease and stroke.
Editors' Summary
Background.
Narrowing of the vessels that take blood to the heart and brain is a common form of cardiovascular disease—i.e., a disorder of the heart and blood vessels. It is a major cause of illness and death. By starving the heart and brain of oxygen, this condition causes coronary heart disease (CHD; heart problems such as angina and heart attacks) and strokes. A major risk factor for CHD and strokes is diabetes, a common chronic disease characterized by high levels of sugar (glucose) in the blood. In people who don't have diabetes, the hormone insulin controls blood-sugar levels. Insulin, which is released by the pancreas after eating, “instructs” insulin-responsive muscle and fat cells to absorb the glucose (released from food) from the bloodstream. In the very early stages of type 2 diabetes (the commonest type of diabetes, also called “adult onset” or “noninsulin-dependent” diabetes”), muscle and fat cells become unresponsive to insulin, so blood-sugar levels increase. This is called “insulin resistance.” The pancreas responds by making more insulin. As a result, people with insulin resistance have high blood levels of both insulin (hyperinsulinemia) and glucose (hyperglycemia). Eventually, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and type 2 diabetes is the result.
Why Was This Study Done?
It is not yet clear whether it is insulin resistance or reduced insulin secretion that is responsible for the association between diabetes and cardiovascular disease. Physicians would like to know this information to help them to prevent CHD and strokes in their patients. There is evidence that variations in fasting glucose levels (blood glucose measured more than 8 h after eating), which provide an indication of how well pancreatic cells are producing insulin, and in fasting insulin levels, which provide an indication of insulin resistance, determine cardiovascular disease risk among people without type 2 diabetes, but the relative importance of these risk factors is unclear. In this study, the researchers have investigated whether markers of insulin resistance (fasting hyperinsulinemia) and of altered insulin secretion (fasting hyperglycemia, and increased glycated hemoglobin, which indicates how much sugar has been in the blood over the past few months) are associated with CHD and strokes in elderly women without diabetes. Their aim is to gain new insights into how diabetes affects cardiovascular disease risk.
What Did the Researchers Do and Find?
The researchers measured glucose, insulin, and glycated hemoglobulin in fasting blood samples taken from about 3,000 women aged 60–79 y when they enrolled in the British Women's Heart and Health Study. None of the women had CHD at enrollment, none had had a stroke, none had diagnosed diabetes, and all had a fasting blood glucose below 7 mmol/l (a higher reading indicates diabetes). After monitoring the women for nearly 5 y for CHD and strokes, the researchers looked for statistical associations between the occurrence of cardiovascular disease and markers of insulin resistance and reduced insulin secretion. They found that fasting insulin levels, but not fasting glucose or glycated hemoglobin levels, were associated with CHD and stroke, even after allowing for other factors that affect cardiovascular disease risk such as smoking and physical activity. In other words, raised fasting insulin levels increased the women's risk of developing cardiovascular disease.
What Do These Findings Mean?
These results indicate that in elderly women without diabetes, fasting insulin (a marker of insulin resistance) is a better predictor of future cardiovascular disease risk than fasting glucose or glycated hemoglobin (markers of reduced insulin secretion). This suggests that insulin resistance might be the main mechanism linking type 2 diabetes to CHD and stroke in elderly women. (Elderly women are known to run a high risk of developing these conditions, but they have been relatively neglected in previous studies of the risk factors for cardiovascular disease.) However, because relatively few women developed CHD during the study and even fewer had a stroke, this conclusion needs confirming in larger studies, preferably ones that include more rigorous tests of insulin resistance and secretion and also include women from more ethnic backgrounds than this study did. If the association between fasting insulin levels and cardiovascular disease risk is confirmed, therapeutic interventions or lifestyle interventions (for example, increased physical activity or weight loss) that prevent or reverse insulin resistance might reduce cardiovascular disease risk better than interventions that prevent chronic hyperglycemia.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040263.
MedlinePlus encyclopedia page on coronary heart disease, stroke, and diabetes (in English and Spanish)
Information for patients and caregivers from the US National Diabetes Information Clearinghouse on diabetes, including information on insulin resistance and on diabetes, heart disease, and stroke
Information on the British Women's Heart and Health Study
doi:10.1371/journal.pmed.0040263
PMCID: PMC1952205  PMID: 17760500
25.  Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life 
Bipolar disorders  2009;11(6):637-649.
Objectives
Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders. We addressed these issues by examining data from a prospective longitudinal community study to (i) determine the cumulative incidence of mood episodes and disorders in the first three decades of life; (ii) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa; and (iii) determine the clinical and treatment characteristics of these subjects.
Methods
Using the Munich-Composite International Diagnostic Interview, clinically trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects (aged 14–24 at baseline and 21–34 at third follow-up).
Results
The estimated cumulative incidence at age 33 was 2.9% for manic, 4.0% for hypomanic, 29.4% for major depressive, and 19.0% for minor depressive episodes; overall, 26.0% had unipolar major depression, 4.0% bipolar depression, 1.5% unipolar mania, and 3.6% unipolar hypomania (no major depression). Overall, 0.6% and 1.8% had unipolar mania or hypomania, respectively, without indication for even minor depression. A total of 3.6% of the initial unipolar major depression cases subsequently developed (hypo)mania, with particularly high rates in adolescent onset depression (< 17 years: 9%). A total of 49.6% of the initial unipolar mania cases subsequently developed major depression and 75.6% major or minor depression. While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases, bipolar cases did not significantly differ in mania characteristics from unipolar mania cases.
Conclusions
Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood, a time period when both the recognition and the intervention rates by the healthcare system are rather low. ‘Conversion’ to bipolar disorder is limited in initial unipolar depression, but common in initial unipolar mania. The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings.
doi:10.1111/j.1399-5618.2009.00738.x
PMCID: PMC2796427  PMID: 19689506
bipolar disorder; community study; conversion; epidemiology; mood episode

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