Jill M. Cyranowski

Evidence of dysregulated peripheral oxytocin release among depressed women.

Objective: Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Methods: Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20-minute baseline, 10-minute task, and 30-minute recovery periods. Results: The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Conclusions: Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women. HPA = hypothalamic-pituitary-adrenal; MDD = major depressive disorder; SCID-IV = Structured Clinical Interview for Axis I DSM-IV disorders; HRSD-17 = 17-item Hamilton Rating Scale for Depression; BDI = Beck Depression Inventory; BAI = Beck Anxiety Inventory; IIP = Inventory of Interpersonal Problems; AUC = area under the curve; pg/ml = picograms per milliliter; CSF = cerebrospinal fluid; PVN = paraventricular nucleus; SON = supraoptic nucleus.

Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN)

BACKGROUND It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders. METHOD Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Womens 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 at 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 a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. 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, VMS 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 pre-menopausal.

Brief Interpersonal Psychotherapy for Depressed Mothers Whose Children Are Receiving Psychiatric Treatment

OBJECTIVE Depressed mothers of children with psychiatric illness struggle with both their own psychiatric disorder and the demands of caring for ill children. When maternal depression remains untreated, mothers suffer, and psychiatric illness in their offspring is less likely to improve. This randomized, controlled trial compared the interpersonal psychotherapy for depressed mothers (IPT-MOMS), a nine-session intervention based on standard interpersonal psychotherapy, to treatment as usual for depressed mothers with psychiatrically ill offspring. METHOD Forty-seven mothers meeting DSM-IV criteria for major depression were recruited from a pediatric mental health clinic where their school-age children were receiving psychiatric treatment and randomly assigned to IPT-MOMS (N=26) or treatment as usual (N=21). Mother-child pairs were assessed at three time points: baseline, 3-month follow-up, and 9-month follow-up. Child treatment was not determined by the study. RESULTS Compared to subjects assigned to treatment as usual, subjects assigned to IPT-MOMS showed significantly lower levels of depression symptoms, as measured by the Hamilton Depression Rating Scale, and higher levels of functioning, as measured by the Global Assessment of Functioning, at 3-month and 9-month follow-ups. Compared to the offspring of mothers receiving treatment as usual, the offspring of mothers assigned to IPT-MOMS showed significantly lower levels of depression as measured by the Childrens Depressive Inventory at the 9-month follow-up. CONCLUSIONS Assignment to IPT-MOMS was associated with reduced levels of maternal symptoms and improved functioning at the 3- and 9-month follow-ups compared to treatment as usual. Maternal improvement preceded improvement in offspring, suggesting that maternal changes may mediate child outcomes.

Schemas, Sexuality, and Romantic Attachment

Ones self-views are powerful regulators of both cognitive processing and behavioral responding. Sexual self-schemas are cognitive generalizations about sexual aspects of the self. The bivariate sexual self-schema model, which posits independent effects of positive and negative components of womens sexual self-views, was tested. Three hundred eighteen female undergraduates completed anonymous questionnaires, including the Sexual Self-Schema Scale and assessments of sexual responses and romantic attachment patterns. Results extended knowledge of positive-negative schema group contrasts and distinguished the response patterns of the aschematic and co-schematic groups. As predicted, aschematics reported low levels of sexual desire, arousal, and anxiety, and weak romantic attachments, whereas co-schematics endorsed conflicting positive and negative responses to sexual-romantic cues. In addition, path analyses supported the bivariate model. Finally, findings are related to theories of attachment representations within the cognitive hierarchy of the self.

Women’s Sexuality: Behaviors, Responses, and Individual Differences

Classic and contemporary approaches to the assessment of female sexuality are discussed. General approaches, assessment strategies, and models of female sexuality are organized within the conceptual domains of sexual behaviors, sexual responses (desire, excitement, orgasm, and resolution), and individual differences, including general and sex-specific personality models. Where applicable, important trends and relationships are highlighted in the literature with both existing reports and previously unpublished data. The present conceptual overview highlights areas in sexual assessment and model building that are in need of further research and theoretical clarification.

Associations between depressive symptoms and inflammatory/hemostatic markers in women during the menopausal transition.

Objective: To test whether depressive symptoms are related to inflammatory and hemostatic markers in women approaching menopause. Methods: A total of 3292 women enrolled in the Study of Womens Health Across the Nation (SWAN) were followed for five years and had measures of Center for Epidemiologic Studies-Depression and high sensitivity C-reactive protein, Factor VIIc, fibrinogen, plasminogen activator inhibitor Type 1(PAI-1), and tissue-type plasminogen activator antigen (tPA-ag) up to four times during the follow-up period. Women were pre- or early perimenopausal status at study entry and were of Caucasian, African American, Hispanic, Japanese, or Chinese race/ethnicity. Results: Unadjusted longitudinal mixed regression models showed that over a 5-year period, higher depressive symptoms were related to higher fibrinogen, PAI-1, and tPA-ag levels, all p < .0001. Taking into account health history, medication use, ethnicity, aging, and menopausal status, the depressive symptoms were related to fibrinogen, p < .01, and PAI-1, p < .05. Depressive symptoms were related only to fibrinogen in models that also included body mass index, p < .05. Conclusions: Depressive symptoms may be associated with cardiovascular risk in perimenopausal women in part through hypercoagulability. This is the first study to test the association of depressive symptoms and hemostatic and inflammatory markers across time. CHD = coronary heart disease; PAI-1 = plasminogen activator inhibitor Type 1; hs-CRP = high sensitivity C-reactive protein; BMI = body mass index; SWAN = Study of Womens Health Across the Nation; CES-D = Center for Epidemiologic Studies-Depression; tPA-ag = tissue-type plasminogen activator antigen; IL = interleukin.

Are there Bi-directional Associations between Depressive Symptoms and C-Reactive Protein in Mid-life Women?

OBJECTIVE To test whether depressive symptoms are related to subsequent C-reactive protein (CRP) levels and/or whether CRP levels are related to subsequent depressive symptoms in mid-life women. METHODS Women enrolled in the Study of Womens Health Across the Nation (SWAN) were followed for 7years and had measures of CES-Depression scores and CRP seven times during the follow-up period. Women were pre- or early peri-menopausal at study entry and were of Caucasian, African American, Hispanic, Japanese, or Chinese race/ethnicity. Analyses were restricted to initially healthy women. RESULTS Longitudinal mixed linear regression models adjusting for age, race, site, time between exams, and outcome variable at year X showed that higher CES-D scores predicted higher subsequent CRP levels and vice versa over a 7-year period. Full multivariate models adjusting for body mass index, physical activity, medications, health conditions, and other covariates showed that higher CRP levels at year X predicted higher CES-D scores at year X+1, p=0.03. Higher depressive symptoms predicted higher subsequent CRP levels at marginally significant levels, p=0.10. CONCLUSIONS Higher CRP levels led to higher subsequent depressive symptoms, albeit the effect was small. The study demonstrates the importance of considering bi-directional relationships for depression and other psychosocial factors and risk for heart disease.

Development of the NIH PROMIS ® Sexual Function and Satisfaction measures in patients with cancer.

INTRODUCTION We describe the development and validation of the Patient-Reported Outcomes Measurement Information System(®) Sexual Function and Satisfaction (PROMIS(®) SexFS; National Institutes of Health) measures, version 1.0, for cancer populations. AIM To develop a customizable self-report measure of sexual function and satisfaction as part of the U.S. National Institutes of Health PROMIS Network. METHODS Our multidisciplinary working group followed a comprehensive protocol for developing psychometrically robust patient-reported outcome measures including qualitative (scale development) and quantitative (psychometric evaluation) development. We performed an extensive literature review, conducted 16 focus groups with cancer patients and multiple discussions with clinicians, and evaluated candidate items in cognitive testing with patients. We administered items to 819 cancer patients. Items were calibrated using item-response theory and evaluated for reliability and validity. MAIN OUTCOME MEASURES The PROMIS SexFS measures, version 1.0, include 81 items in 11 domains: Interest in Sexual Activity, Lubrication, Vaginal Discomfort, Erectile Function, Global Satisfaction with Sex Life, Orgasm, Anal Discomfort, Therapeutic Aids, Sexual Activities, Interfering Factors, and Screener Questions. RESULTS In addition to content validity (patients indicate that items cover important aspects of their experiences) and face validity (patients indicate that items measure sexual function and satisfaction), the measure shows evidence for discriminant validity (domains discriminate between groups expected to be different) and convergent validity (strong correlations between scores on PROMIS and scores on conceptually similar older measures of sexual function), as well as favorable test-retest reliability among people not expected to change (interclass correlations from two administrations of the instrument, 1 month apart). CONCLUSIONS The PROMIS SexFS offers researchers a reliable and valid set of tools to measure self-reported sexual function and satisfaction among diverse men and women. The measures are customizable; researchers can select the relevant domains and items comprising those domains for their study.

Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro

One potential pathway by which depression may impact health is through modulation of immune function. Depressed individuals have been shown to display reductions in measures of cellular immune competence as well as elevated markers of systemic inflammation. The current study assessed the in vitro production of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha by peripheral blood mononuclear cells (PBMCs) in response to mitogen stimulation within a community-based sample of 79 midlife women. Results indicate that midlife women with higher levels of depressive symptoms (as assessed with the Center for Epidemiologic Studies Depression scale) and greater body mass index (BMI) displayed diminished production of IL-6, IL-1beta, and TNF-alpha by stimulated PBMCs, as compared with their less-depressed counterparts. These relationships remained after controlling for such health-related variables as age, recent sleep disruption, physical activity level, and self-reported medical history. In contrast, depressive symptoms were not significantly associated with circulating levels of the same proinflammatory cytokines (IL-6, IL-1beta, and TNF-alpha) obtained from serum samples available for a subset of 62 of the study participants. Moreover, circulating proinflammatory cytokine levels were not significantly associated with the in vitro proinflammatory cytokine production outcomes. Further research is needed to clarify the clinical significance of the current study findings, and the extent to which in vitro tests of stimulated proinflammatory cytokine production are associated with other measures of cellular immune function and/or circulating markers of systemic inflammation obtained across various study populations.

Adult separation anxiety: psychometric properties of a new structured clinical interview

Separation anxiety has traditionally been characterized and assessed as a disorder that is unique to childhood. Yet the core symptoms of separation anxiety, i.e. excessive and often disabling distress when faced with actual or perceived separation from major attachment figures, may persist or even arise during adulthood. We report on the psychometric properties of a new structured clinical interview designed to assess symptoms of separation anxiety as experienced both during childhood and adulthood. This instrument, called the Structured Clinical Interview for Separation Anxiety Symptoms (or SCI-SAS), was administered as part of an assessment battery to 91 adult psychiatric outpatients and 20 non-psychiatric controls. Results indicate that this instrument displays excellent psychometric properties, including good internal consistency, a clear factor structure, and exceptional levels of convergent and discriminate validity. These results highlight the feasibility and potential clinical utility of assessing age-appropriate symptoms of separation anxiety experienced during adulthood.