Objectives

We sought to obtain preliminary data regarding the efficacy of omega-3 fatty acids for major depressive disorder associated with the menopausal transition. Secondary outcomes were assessed for vasomotor symptoms (or hot flashes).

Methods

After a single-blind placebo lead-in, participants received 8 weeks of treatment with open-label omega-3 fatty acid capsules (eicosapentaenoic acid and docosahexaenoic acid, 2 g/d). The Montgomery-Asberg Depression Rating Scale (MADRS) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries and the Hot Flash Related Daily Interference Scale. Blood samples for plasma pretreatment and post treatment essential fatty acid assays were obtained. Because of the small sample size, data were analyzed using nonparametric techniques.

Results

Of 20 participants treated with omega-3 fatty acids, 19 (95%) completed the study. None discontinued because of adverse effects. The pretreatment and final mean MADRS scores were 24.2 and 10.7, respectively, reflecting a significant decrease in MADRS scores (P G 0.0001). The response rate was 70% (MADRS score decrease of Q50%), and the remission rate was 45% (final MADRS score of e7). Responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders did (P = 0.03). Hot flashes were present in 15 (75%) participants. Among those with hot flashes at baseline, the number of hot flashes per day improved significantly from baseline (P = 0.02) and Hot Flash Related Daily Interference Scale scores decreased significantly (P = 0.006).

Conclusions

These data support further study of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition.

This unit describes techniques and approaches that can be used to study the functions of the ADP-ribosylation factor (Arf) GTP-binding proteins in cells. There are 6 mammalian Arfs and many more Arf-like proteins (Arls) and these proteins are conserved in eukaryotes from yeast to man. Like all GTPases, Arfs cycle between GDP-bound, inactive and GTP-bound active conformations, facilitated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) that catalyze GTP binding and hydrolysis respectively. Here we describe approaches that can be taken to examine the localization and function of Arf and Arl proteins in cells (Protocol 1). We also provide a simple protocol for measuring activation (GTP-binding) of specific Arf proteins in cells using a pull-down assay (Protocol 2). We then discuss approaches that can be taken to assess function of GEFs and GAPs in cells (Protocol 3).

Context

Concerns for the risks of hormone therapy have resulted in its decline and a demand for non-hormonal treatments with demonstrated efficacy for hot flashes.

Objective

Determine the efficacy and tolerability of 10–20 mg/day escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity and bother of menopausal hot flashes.

Design, Setting and Patients

Randomized, double-blind, placebo-controlled, parallel arm trial for 8 weeks in a sample stratified by race (African American n=95; white n=102) and conducted at 4 MsFlash network sites between July 2009 and June 2010. Of 205 women randomized, 194 (95%) completed week 8 (intervention endpoint), and 183 completed post-treatment follow-up.

Main Outcome Measures

Primary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries. Secondary outcomes were hot flash "bother" recorded on daily diaries and clinical improvement (hot flash frequency >=50% decrease from baseline).

Results

Hot flash frequency was 9.78/day (SD 5.60) at baseline. At week 8, reduction in hot flash frequency was greater in the escitalopram group versus placebo (−4.60, SD 4.28 and −3.20, SD 4.76, respectively, P=0.004). Fifty-five percent of the escitalopram group (versus 36% of the placebo group) reported >=50% decreases in hot flash frequency (P=0.009). Differences in decreases in the severity and bother of hot flashes were significant (P=0.003 and P=0.013, respectively), paralleling the decreases in hot flash frequency. Three weeks after treatment ended, hot flash frequency increased in the escitalopram group to the level of the placebo group, which remained stable in the follow-up interval (P=0.020). Overall discontinuation due to side effects was 4% (7 drug, 2 placebo).

Conclusion

Escitalopram 10–20 mg/day provides non-hormonal off-label treatment for menopausal hot flashes that is effective and well-tolerated in healthy women.

Backgroud

Peripartum major depressive disorder (MDD) is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population.

Methods

274 women with a prior history of MDD were genotyped for 5-HTTLPR and serially evaluated in late pregnancy (gestational weeks 31-40), early postpartum (week 1-8) and late postpartum (week 9-24) for diagnosis of a current major depressive episode (MDE) and depressive symptom severity.

Results

5-HTTLPR S-allele carrier status predicted the occurrence of a MDE in the early postpartum period only (OR = 5.13, p = 0.017). This association persisted despite continued antidepressant treatment.

Conclusions

The 5-HTTLPR genotype may be a clinically relevant predictor of early postpartum depression in an at-risk population.

This study examined the association between vulnerability to depression and smoking behavior in college students in 1214 college students (54% female), and evaluated gender and expectancies of negative affect reduction as moderators or mediators of this relationship. Depression vulnerability predicted smoking in females, but not males. The relationship between depression vulnerability and smoking status was mediated by expectancies of negative affect reduction in females only. Female college students who are vulnerable to depression may smoke because they expect smoking to relieve negative affect. Smoking interventions for college females may increase in effectiveness by targeting depression and emphasizing mood regulation.

Objective

Approximately 6–8% of postpartum women suffer from major depressive disorder (MDD) but only a few controlled trials have investigated the efficacy of pharmacological treatments. The current study determined the relative efficacy of paroxetine compared to placebo in the treatment of acute postpartum MDD.

Method

This was an 8-week, multi-center, parallel, placebo-controlled trial of paroxetine for treatment of postpartum depression. Subjects were eligible if they had an onset of MDD after, but within 3 months of delivery and had a minimum score of 16 on the 17-item Hamilton Rating Scale for Depression (HRS-D17) at intake. Seventy women were randomly assigned to either immediate-release paroxetine or matching placebo and 31 completed the trial. Subjects were reassessed with the HRS-D17, the Inventory of Depressive Symptomatology-Self Report (IDS-SR) form and the Clinical Global Impression (CGI) Scales.

Results

Both groups improved over time and did not differ significantly on HRS-D17 or the IDS-SR at follow-up. However, greater improvement in overall clinical severity was found for the paroxetine (CGI-S =1.8 ±1.4) compared with the control group (CGI-S=3.1 ± 1.4; p=0.05). The paroxetine group also had a significantly higher rate of remission, compared to the placebo group (37% vs 15%; OR=3.5; 95% CI = 1.1–11.5). The rate of adverse effects did not differ significantly between groups.

Conclusion

Study results were limited by lower than expected enrollment and higher than anticipated attrition. Nonetheless, paroxetine treatment was associated with a significantly higher rate of remission among women with postpartum onset of MDD.

In a prospective, longitudinal, population-based study of 643 women participating in the Harvard Study of Moods and Cycles we examined whether psychosocial variables predicted a new or recurrent onset of an anxiety disorder. Presence of anxiety disorders was assessed every six months over three years via structured clinical interviews. Among individuals who had a new episode of anxiety, we confirmed previous findings that history of anxiety, increased anxiety sensitivity (the fear of anxiety related sensations), and increased neuroticism were significant predictors. We also found trend level support for assertiveness as a predictor of anxiety onset. However, of these variables, only history of anxiety and anxiety sensitivity provided unique prediction. We did not find evidence for negative life events as a predictor of onset of anxiety either alone or in interaction with other variables in a diathesis-stress model. These findings from a prospective longitudinal study are discussed in relation to the potential role of such predictors in primary or relapse prevention efforts.

Introduction

The aim of this prospective repeated measures, mixed-methods observational study was to assess whether depressive, anxiety, and stress symptoms are associated with postpartum relapse to smoking.

Methods

A total of 65 women who smoked prior to pregnancy and had not smoked during the last month of pregnancy were recruited at delivery and followed for 24 weeks. Surveys administered at baseline and at 2, 6, 12, and 24 weeks postpartum assessed smoking status and symptoms of depression (Beck Depression Inventory [BDI]), anxiety (Beck Anxiety Inventory [BAI]), and stress (Perceived Stress Scale [PSS]). In-depth interviews were conducted with women who reported smoking.

Results

Although 92% of the participants reported a strong desire to stay quit, 47% resumed smoking by 24 weeks postpartum. Baseline factors associated with smoking at 24 weeks were having had a prior delivery, not being happy about the pregnancy, undergoing counseling for depression or anxiety during pregnancy, and ever having struggled with depression (p < .05). In a repeated measures regression model, the slope of BDI scores from baseline to the 12-week follow-up differed between nonsmokers and smokers (−0.12 vs. +0.11 units/week, p = .03). The slope of PSS scores also differed between nonsmokers and smokers (−0.05 vs. +0.08 units/week, p = .04). In qualitative interviews, most women who relapsed attributed their relapse and continued smoking to negative emotions.

Discussion

Among women who quit smoking during pregnancy, a worsening of depressive and stress symptoms over 12 weeks postpartum was associated with an increased risk of smoking by 24 weeks.

There is increasing interest in endocytosis that occurs independently of clathrin coats and the fates of membrane proteins internalized by this mechanism. The appearance of clathrin-independent endocytic and membrane recycling pathways seems to vary with different cell types and cargo molecules. In this review we focus on studies that have been performed using Hela and COS cells as model systems for understanding this membrane trafficking system. These endosomal membranes contain signaling molecules including H-Ras, Rac1, Arf6 and Rab proteins, and a lipid environment rich in cholesterol and PIP2 providing a unique platform for cell signaling. Furthermore, activation of some of these signaling molecules (H-Ras, Rac and Arf6) can switch the constitutive form of clathrin-independent endocytosis into a stimulated one, associated with PM ruffling and macropinocytosis.

Approximately 10,000 undergraduates from 12 Texas colleges and universities and 350 health care students completed a Web-based survey assessing the prevalence and awareness of cigarette smoking. There were few differences between health care and undergraduate students on trying smoking or quitting smoking. Health care students reported lower rates of current smoking than undergraduate students, even though both groups demonstrated similar knowledge of tobacco-related health risks. Gender differences are discussed. Findings suggest that tobacco awareness programs should continue to target young adults as an at-risk population, and that health care training programs should place a greater emphasis on tobacco cessation.

Objective

Prenatal antidepressant use has been associated with shorter pregnancy duration and an increased risk for preterm birth. This study measured saliva levels of estriol, a hormone which increases exponentially in the few weeks before spontaneous labor, in pregnant women with and without antidepressant treatment.

Method

Saliva estriol levels were obtained across the day at three time points during pregnancy in 77 subjects with either a history of DSM-IV major depressive disorder (MDD) who were treated with antidepressants in pregnancy (Group 1), a history of DSM-IV major depressive disorder who were not treated or had limited exposure to antidepressants during pregnancy (Group 2), and a normal control group (Group 3).

Results

Mean estriol levels in the second half of pregnancy were significantly higher for Group 1 (h/o MDD, on meds) than Group 2 (h/o MDD, off meds) or Group 3 (control).

Conclusions

Prenatal antidepressant use was associated with significantly higher saliva estriol levels in the second half of pregnancy. Whether estriol reflects a causal mechanism by which women on antidepressants have shorter pregnancy duration remains to be further studied.

ARNO is a soluble guanine nucleotide exchange factor (GEF) for the Arf family of GTPases. Although in biochemical assays ARNO prefers Arf1 over Arf6 as a substrate, its localization in cells at the plasma membrane (PM) suggests an interaction with Arf6. In this study, we found that ARNO activated Arf1 in HeLa and COS-7 cells resulting in the recruitment of Arf1 on to dynamic PM ruffles. By contrast, Arf6 was activated less by ARNO than EFA6, a canonical Arf6 GEF. Remarkably, Arf6 in its GTP-bound form recruited ARNO to the PM and the two proteins could be immunoprecipitated. ARNO binding to Arf6 was not mediated through the catalytic Sec7 domain, but via the pleckstrin homology (PH) domain. Active Arf6 also bound the PH domain of Grp1, another ARNO family member. This interaction was direct and required both inositol phospholipids and GTP. We propose a model of sequential Arf activation at the PM whereby Arf6-GTP recruits ARNO family GEFs for further activation of other Arf isoforms.

Background

Although tobacco use in the United States has declined over the past 20 years, cigarette use among college students remains high. Additional research is thus needed to determine how university tobacco control policies and preventive education programs affect college students' smoking behaviors.

Methods

Approximately 13,000 undergraduate students at 12 universities or colleges in the state of Texas completed a web-based survey. College smoking policies were obtained from a survey of college administrators and from college websites. Logistic regression analyses were conducted to estimate the effects of individual smoking policies and programs on the odds of cigarette smoking.

Results

Of the individual programs, only having a preventive education program on campus was associated with lower odds of smoking. The existence of smoking cessation programs and designated smoking areas were associated with higher odds of smoking. Policies governing the sale and distribution of cigarettes were insignificantly associated with smoking.

Conclusion

Rather than focusing on policies restricting cigarette sales and use, college administrators should consider implementing or expanding tobacco prevention and education programs to further reduce student smoking rates.