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Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences. ClinicalTrials.gov NCT00006180.

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Roger E. Meyer for his comments on earlier drafts of this paper and to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided invaluable guidance throughout all stages of this project, as well as Robert Asarnow, who was an important mentor during the review process. In addition, we acknowledge the contributions of Gail Inoff–Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

The mortality of chronic heart failure (CHF) doubles either when CHF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by ≈40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed basal and stress-mediated arterial NE appearance. Severely depressed patients had significant increases in mean around-the-clock levels of CSF NE (P < 0.02), plasma NE (P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF NE, plasma NE, and cortisol all rose together throughout the night and peaked in the morning. Each fell to control values after ECT. Mildly-to-moderately melancholic patients also had increased basal (P < 0.05) and stress-related (P < 0.03) arterial NE-appearance rates. Severely melancholic depressed, medication-free patients had around-the-clock increases in plasma NE levels capable of increasing mortality in CHF. Twenty-four-hour indices of central noradrenergic, adrenomedullary, and adrenocortical secretion were also elevated. Concurrent diurnal rhythms of these secretions could potentiate their cardiotoxicity. Even mildly-to-moderately depressed melancholic patients had clinically relevant increases in the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression.

There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at- risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.

Individuals with melancholic major depression exhibit basal hypercortisolism and an attenuated ACTH response to exogenous corticotropin-releasing hormone (CRH) infusion. Given the greater incidence of depression in children of depressed parents, we examined the ACTH and cortisol responses to ovine CRH (oCRH) infusion in 63 adolescent offspring of mothers with major depression, bipolar illness, or no psychiatric illness. Psychiatric and observational assessments of these families had been conducted over the course of 10 years preceding this study. We examined the children's responses to CRH in relation to maternal characteristics and family environment and found the following: (a) cortisol responses were negatively related to chronic family stress and (b) offspring of depressed mothers with an avoidant personality disorder showed an exaggerated ACTH response. In addition, adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to oCRH infusion than those in early puberty. Further, offspring with early histories of mood problems, and those who developed major depressive disorder as young adults, did not exhibit basal hypercortisolism but did show an attenuated ACTH response to CRH. Our results add to the growing body of literature showing the influence of maternal characteristics and environmental factors on hypothalamic–pituitary–adrenal axis patterns in children.We acknowledge the efforts of our predecessors on this project, whose work made this study possible. In addition, we thank Ann Mayfield, Sara Torvik, and Patricia Kasdan for their recruitment efforts and Sue Harris and Hayley Kleitz for their editorial comments on the manuscript. Finally, we thank all of the mothers and their children who have dedicated their time to this study over the course of 20 years.

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability–stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided support and guidance throughout all stages of this project. We are also thankful to Robert Asarnow for his advice and encouragement, and to Roger E. Meyer and Daniel N. Klein for their comments on earlier drafts of this paper. In addition, we acknowledge the contributions of Gail Inoff-Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

OBJECTIVES: This study sought to estimate the rate of compliance with American Academy of Pediatrics guidelines for well child care in the first 6 months of life and to determine risks for inadequate care. METHODS: The study included 7776 infants whose mothers participated in both the 1988 National Maternal and Infant Health Survey and its 1991 longitudinal follow-up and whose mothers or pediatric providers supplied information about their medical care. Regression analysis was used to determine the probability of incomplete compliance with guidelines for well child care in relation to several socioeconomic risks. RESULTS: Fifty-eight percent of White infants, 35% of African American infants, and 37% of Hispanic infants obtained all recommended well child care. African American race was the biggest risk for inadequate care (odds ratio = 1.7, 95% confidence interval = 1.5, 1.9), followed by low levels of maternal education, low income, and poor prenatal care. The risk for African American infants persisted across socioeconomic levels. CONCLUSIONS: The racial disparities identified suggest that cultural barriers to seeking preventive care need further study and that programs aimed at reducing these barriers need to be developed.

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.