The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Iron Deficiency and Risk of Maternal Depression in Pregnancy: An Observational Study.

OBJECTIVE: Maternal depression during pregnancy can affect both the mother and her family. Although research has suggested that iron deficiency is associated with depression in the general population, this link has not been examined during the antenatal period. Our objective was to determine whether iron deficiency is associated with maternal depression during middle to late pregnancy. METHODS: A retrospective study was conducted using the medical records of patients seen at the Women's Health Concerns Clinic at St. Joseph's Healthcare Hamilton in Hamilton, Ontario between 2009 and 2016. Women with serum ferritin data during middle to late pregnancy (>20 weeks' gestation) (N = 142) were categorized as either iron deficient (ferritin <12 µg/L) or iron sufficient. Edinburgh Postnatal Depression Scale (EPDS) scores and the odds of developing antenatal depression (EPDS ≥12) between the two groups were compared. RESULTS: Iron deficient pregnant women scored significantly higher on the EPDS (10.14 ± 5.69 vs. 7.87 ± 5.75; P = 0.03) and were more likely to develop antenatal depression (45% vs. 25%; P = 0.02) compared with women who were not. The odds of developing antenatal depression were two and one half times higher among iron deficient women (adjusted OR 2.51; 95% CI 1.14-5.52). CONCLUSION: These findings suggest that iron deficiency is associated with higher levels of depression during pregnancy. Although these results require replication, iron deficiency may be an important risk factor for maternal depression during pregnancy.

Association between cannabis use and methadone maintenance treatment outcomes: an investigation into sex differences.

BACKGROUND: Cannabis will soon become legalized in Canada, and it is currently unclear how this will impact public health. Methadone maintenance treatment (MMT) is the most common pharmacological treatment for opioid use disorder (OUD), and despite its documented effectiveness, a large number of patients respond poorly and experience relapse to illicit opioids. Some studies implicate cannabis use as a risk factor for poor MMT response. Although it is well established that substance-use behaviors differ by sex, few of these studies have considered sex as a potential moderator. The current study aims to investigate sex differences in the association between cannabis use and illicit opioid use in a cohort of MMT patients. METHODS: This multicentre study recruited participants on MMT for OUD from Canadian Addiction Treatment Centre sites in Ontario, Canada. Sex differences in the association between any cannabis use and illicit opioid use were investigated using multivariable logistic regression. A secondary analysis was conducted to investigate the association with heaviness of cannabis use. RESULTS: The study included 414 men and 363 women with OUD receiving MMT. Cannabis use was significantly associated with illicit opioid use in women only (OR = 1.82, 95% CI 1.18, 2.82, p = 0.007). Heaviness of cannabis use was not associated with illicit opioid use in men or women. CONCLUSIONS: This is the largest study to date examining the association between cannabis use and illicit opioid use. Cannabis use may be a sex-specific predictor of poor response to MMT, such that women are more likely to use illicit opioids if they also use cannabis during treatment. Women may show improved treatment outcomes if cannabis use is addressed during MMT.

A statistical method to calculate blood contamination in the measurement of salivary hormones in healthy women.

OBJECTIVES: Previous studies have reported that salivary concentrations of certain hormones correlate with their respective serum levels. However, most of these studies did not control for potential blood contamination in saliva. In the present study we developed a statistical method to test the amount of blood contamination that needs to be avoided in saliva samples for the following hormones: cortisol, estradiol, progesterone, testosterone and oxytocin. DESIGN & METHODS: Saliva and serum samples were collected from 38 healthy, medication-free women (mean age=33.8±7.3yr.; range=19-45). Serum and salivary hormonal levels and the amount of transferrin in saliva samples were determined using enzyme immunoassays. RESULTS: Salivary transferrin levels did not correlate with salivary cortisol or estradiol (up to 3mg/dl), but they were positively correlated with salivary testosterone, progesterone and oxytocin (p<0.05). After controlling for blood contamination, only cortisol (r=0.65, P<0.001) and progesterone levels (r=0.57, P=0.002) displayed a positive correlation between saliva and serum. Our analyses suggest that transferrin levels higher than 0.80, 0.92 and 0.64mg/dl should be avoided for testosterone, progesterone and oxytocin salivary analyses, respectively. CONCLUSIONS: We recommend that salivary transferrin is measured in research involving salivary hormones in order to determine the level of blood contamination that might affect specific hormonal salivary concentrations.

Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology of Obsessive-Compulsive Disorder: A Critical Review.

Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric disorder affecting between 1.6 and 3.2% of the population. A number of studies have previously reported increased incidence of OCD, or exacerbation of preexisting symptoms in females during reproductive events. Since these periods are known to involve fluctuating levels of gonadal hormones, these steroids have been suggested to be involved in modulating the course of the disorder. However, to date, only a few studies have measured hormone levels and obsessive-compulsive (OC) symptoms concurrently; thus, direct evidence for this relationship is limited. In turn, investigations into neurotransmission in OC individuals have been more extensive, and have implicated the serotonergic, dopaminergic, and glutamatergic neurotransmitter systems in OCD pathology. There is evidence suggesting that reproductive hormones estrogens and progesterone can modulate neurotransmission in the aforementioned signaling pathways by regulating the expression of receptors and channels, as well as the synthesis and release of the neurotransmitter itself. Overall, estrogen and progesterone appear to enhance serotonin signaling, which has been associated with improved OC symptoms. The effect of the gonadal hormones in dopaminergic and glutamatergic signaling is much more variable, highlighting the need for further research in this field. The existing evidence shows that gonadal hormones can have profound impacts on neurotransmission in the brain, leading to the conclusion that the hormonal fluctuations during reproductive events are a plausible factor contributing to the change in OCD course during these times.

Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study.

OBJECTIVE: Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. METHODS: Thirty-three healthy pregnant women were recruited from the Women's Health Concerns Clinic at St. Joseph's Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. RESULTS: Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. CONCLUSIONS: Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study

Objective: Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Methods: Thirty-three healthy pregnant women were recruited from the Women’s Health Concerns Clinic at St. Joseph’s Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Results: Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. Conclusions: Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

Association between cannabis use and treatment outcomes in patients receiving methadone maintenance treatment: a systematic review protocol.

BACKGROUND: With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups. METHODS/DESIGN: The search will be conducted on the following electronic databases using a predefined search strategy: MEDLINE, EMBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two authors (LZ and MB) will independently screen articles using predetermined inclusion/exclusion criteria and will extract data from included articles using a pilot-tested data extraction form. Disagreements at all stages of the screening process will be settled through discussion, and when consensus cannot be reached, a third author (ZS) will be consulted. An assessment of quality and risk of bias will be conducted on all included articles, and a sensitivity analysis will be used to compare results of studies with high and low risk of bias. We will perform random- and fixed-effects meta-analyses, if appropriate, with heterogeneity calculated using the I (2) statistic and formal evaluation of publication bias. DISCUSSION: Results of this systematic review will elucidate the association between cannabis use and methadone maintenance treatment outcomes. We will provide evidence that will be useful to clinicians regarding whether monitoring cannabis use during MMT is advantageous for optimizing MMT outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029372.

Genetic Differential Susceptibility to Socioeconomic Status and Childhood Obesogenic Behavior: Why Targeted Prevention May Be the Best Societal Investment.

IMPORTANCE: Genes may work by modulating the way individuals respond to environmental variation, and these discrete and differential genes vs environmental interactions may not be readily captured in simple association studies. OBJECTIVE: To determine whether children carrying the 7-repeat allele of the DRD4 gene living under adverse economic conditions have worse-than-average fat intake compared with those living in a healthy environment. DESIGN, SETTING, AND PARTICIPANTS: Data from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were used to study 4-year-old children from Montreal, Quebec, Canada and Hamilton, Ontario, Canada. A total of 190 children (94 girls and 96 boys) had height and weight measured and complete food diaries and were therefore eligible for the study. The study is derived from a birth cohort started in June 2003 and still ongoing. The last age of follow-up was at 6 years. EXPOSURES: Social environment was characterized based on the gross family income, and DNA was genotyped for the 7-repeat allele of the DRD4 gene. MAIN OUTCOMES AND MEASURES: Fat intake. RESULTS: The 5 steps to distinguish the differential susceptibility from other types of interaction were followed, and the study confirms that differential susceptibility is a relevant model to address the association between the 7-repeat allele of DRD4 and food choices in girls. Of the 190 children, 112 did not have the DRD4 7-repeat allele and 78 did. Baseline characteristics did not differ in these 2 groups. Although not different in several confounders, such as maternal educational level, maternal smoking during gestation, birth weight, and breastfeeding duration, girls carrying the 7-repeat allele of the DRD4 gene and living in adverse socioeconomic conditions have increased fat intake compared with girls who are noncarriers (DRD4 7+ mean, 33.95% of calories derived from fat; 95% CI, 28.76%-39.13%; DRD4 7- mean, 28.76%; 95% CI, 26.77%-30.83%). However, girls carrying the 7-repeat allele of the same gene and living in better socioeconomic conditions have decreased fat intake compared with noncarriers (DRD4 7+ mean, 29.03% of calories derived from fat; 95% CI, 26.69%-31.51%; DRD4 7- mean, 31.88%; 95% CI, 30.28%-33.58%). CONCLUSIONS AND RELEVANCE: Alleles previously considered to be obesity risk alleles might in fact function as plasticity alleles, determining openness to environmental modification and/or intervention, as seen in the girls in this study. This finding has important implications for obesity prevention and social pediatrics.

Sex differences in substance use, health, and social functioning among opioid users receiving methadone treatment: a multicenter cohort study.

BACKGROUND: Despite the growing numbers of men and women with opioid use disorder in Canada, sex-specific issues in treatment have not been re-examined in the current population of patients with opioid addiction. We aimed to evaluate sex differences in substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid use disorder in Ontario, Canada. METHODS: We recruited 503 participants with opioid dependence disorder receiving methadone maintenance treatment. We collected data on demographics, treatment characteristics, psychiatric history, addiction severity, and drug use patterns through urinalysis. We performed adjusted univariate analyses and logistic regression to identify distinct factors affecting men and women. RESULTS: Among our sample of 54 % (n = 266) men and 46 % women (n = 226) with mean age 38.3 years, less than half of participants were employed (35.6 %) and married (31.8 %) and had completed a high school education (27.9 %). Compared to men, women had frequent physical and psychological health problems, family history of psychiatric illness, and childcare responsibilities and began using opioids through a physician prescription. Men had higher rates of employment, cigarette smoking, and cannabis use compared to women. CONCLUSIONS: Our results have revealed different patterns of substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid addiction in Ontario, Canada. This information can be used to develop an integrative treatment regimen that caters to the individual needs of men and women, as well as to inform methadone treatment protocols to include specialized services (including vocational counseling, childcare and parenting assistance, medical assistance, relationship or domestic violence counseling, etc.) and increase their availability and accessibility on a larger scale.

Working memory in pregnant women: Relation to estrogen and antepartum depression.

This article is part of a Special Issue "Estradiol and cognition". Subjective changes in concentration and memory are commonly reported by women during the second or third trimesters of pregnancy, but the nature of the problem is poorly understood. We hypothesized that these self-reports might reflect difficulties in working memory (WM). It was further hypothesized that antepartum depression (depression arising during pregnancy) may play an etiological role, either on its own or due to secondary changes in endocrine function or sleep. Using WM tasks that emphasized executive control processes mediated by the prefrontal cortex (PFC) we compared pregnant women tested at 34-36 weeks of gestation (n = 28) with age- and education-matched non-pregnant controls (n = 26). All pregnant women were screened for depression. Evidence of a WM disturbance was found, and was evident only among pregnant women showing depressive symptoms. In contrast, pregnant women who were not depressed showed WM performance that equalled, or even significantly exceeded, non-pregnant controls. No significant differences were observed on control tests of other cognitive functions. Multiple regression revealed that serum estradiol concentrations, along with severity of depressive affect but not sleep disruption, significantly predicted variation in the WM scores. In agreement with studies of estradiol and WM in other contexts, higher estradiol was associated with better WM, while higher levels of depressive symptoms predicted poorer WM. We conclude that memory disturbance during gestation might not be as widespread as commonly believed, but can be seen among women experiencing antepartum depression. The high level of WM performance found in healthy, non-depressed, pregnant women is discussed from an adaptationist perspective.

Comparative efficacy of the generalized anxiety disorder 7-item scale and the Edinburgh Postnatal Depression Scale as screening tools for generalized anxiety disorder in pregnancy and the postpartum period.

OBJECTIVE: About 24.1% of pregnant women suffer from at least 1 anxiety disorder, 8.5% of whom suffer specifically from generalized anxiety disorder (GAD). GAD is often associated with major depressive disorder (MDD). During the perinatal period, the presence of physical and somatic symptoms often makes differentiation between depression and anxiety more challenging. To date, no screening tools have been developed to detect GAD in the perinatal population. We investigated the psychometric properties of the GAD 7-item Scale (GAD-7) as a screening tool for GAD in pregnant and postpartum women. METHODS: Two hundred and forty perinatal women (n = 155 pregnant and n = 85 postpartum) referred for psychiatric consultation were enrolled. On the day of initial assessment, all women completed the GAD-7 and the Edinburgh Postnatal Depression Scale (EPDS). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based diagnoses were made by experienced psychiatrists. Scores from the GAD-7 and EPDS were compared with the clinical diagnoses to evaluate the psychometric properties of the GAD-7 and EPDS when used as a screening tool for GAD. RESULTS: The GAD-7 yielded a sensitivity of 61.3% and specificity of 72.7% at an optimal cut-off score of 13. Compared with the EPDS and the EPDS-3A subscale, the GAD-7 displayed greater accuracy and specificity over a greater range of cut-off scores and more accurately identified GAD in patients with comorbid MDD. CONCLUSION: Our findings suggest that the GAD-7 represents a clinically useful scale for the detection of GAD in perinatal women.

Association between the seven-repeat allele of the dopamine-4 receptor gene (DRD4) and spontaneous food intake in pre-school children.

BACKGROUND: Studies in adults show associations between the hypofunctional seven-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), increased eating behaviour and/or obesity, particularly in females. We examined whether 7R is associated with total caloric intake and/or food choices in pre-schoolers. METHODS: 150 four-year-old children taking part in a birth cohort study in Canada were administered a snack test meal in a laboratory setting. Mothers also filled out a food frequency questionnaire to address childrens' habitual food consumption. Total caloric and individual macronutrient intakes during the snack meal and specific types of foods as reported in the food diaries were compared across 7R allele carriers vs. non-carriers, using current BMI as a co-variate. RESULTS: We found significant sex by genotype interactions for fat and protein intake during the snack test. Post hoc testing revealed that in girls, but not boys, 7R carriers ate more fat and protein than did non-carriers. Based on the food diaries, across both sexes, 7R carriers consumed more portions of ice cream and less vegetables, eggs, nuts and whole bread, suggesting a less healthy pattern of habitual food consumption. CONCLUSION: The 7R allele of DRD4 influences macronutrient intakes and specific food choices as early as four years of age. The specific pattern of results further suggests that prior associations between the 7R allele and adult overeating/obesity may originate in food choices observable in the preschool years. Longitudinal follow-up of these children will help establish the relevance of these findings for obesity risk and prevention.

Association study of the estrogen receptor gene ESR1 with postpartum depression--a pilot study.

Perinatal mood disorders, such as postpartum depression (PPD), are costly for society, with potentially serious consequences for mother and child. While multiple genes appear to play a role in PPD susceptibility, the contributions of specific genetic variations remain unclear. Previously implicated as a candidate gene, the estrogen receptor alpha gene (ESR1) is a key player in mediating hormonal differences during pregnancy and the postpartum period. This study addresses genetic factors in perinatal mood disorders, testing nine polymorphisms in ESR1. Two hundred fifty-seven postpartum women were screened for mood disorders, including 52 women with PPD and 32 without any symptoms of mood disorders. We detected a significant association for the upstream TA microsatellite repeat with Edinburgh Postnatal Depression Scale scores (p = 0.007). The same variant was also associated with the occurrence of PPD. Separately, 11 candidate functional polymorphisms in 7 additional genes were genotyped to investigate gene-gene interaction with the ESR1 TA repeat, identifying a potential interaction with the serotonin transporter. Our results support a role for ESR1 in the etiology of PPD, possibly through the modulation of serotonin signaling. Our findings for ESR1 could have broad implications for other disorders and therapies that involve estrogens.

Sensitivity and specificity of the Mood Disorder Questionnaire as a screening tool for bipolar disorder during pregnancy and the postpartum period.

BACKGROUND: Previous studies have shown that one-quarter of women with bipolar disorder relapse during pregnancy, and nearly half of bipolar women relapse during the postpartum period. The perinatal period is also associated with an elevated risk for new-onset mood disorder. Bipolar disorder is often unrecognized, and there is often a significant delay between illness onset and proper diagnosis and treatment. The objective of this cross-sectional psychometric study was to investigate the use of the Mood Disorder Questionnaire (MDQ) as a screening tool for bipolar disorder in a community-based population of pregnant and postpartum women. METHOD: 150 women with a mean age of 30.1 years (standard deviation = 5.5 years; range, 17-43 years) who had been referred to a women's mental health program for psychiatric assessment during pregnancy (n = 95) or the postpartum period (n = 55) were enrolled between June 2010 and December 2011. All women completed the MDQ on the day of their first assessment, and the sensitivity and specificity of the MDQ were calculated against DSM-IV-based clinical diagnoses provided by experienced psychiatrists. RESULTS: A total of 18 women (12% of the sample) were diagnosed with bipolar disorder (6 with bipolar I disorder, 10 with bipolar II disorder, and 2 with bipolar disorder not otherwise specified). The traditional scoring of the MDQ yielded poor sensitivity (39%) and excellent specificity (91%). The best-fitting model was a modified scoring algorithm using cutoff scores of 7 or more symptoms on the MDQ without the supplementary questions, yielding excellent sensitivity (89%) and specificity (84%). CONCLUSIONS: The MDQ is a useful instrument for screening for bipolar disorder during both pregnancy and the postpartum period. Considering that perinatal women have an elevated risk of both first-onset and relapse of bipolar disorder, particularly during the postpartum period, routine use of screening tools in perinatal programs is encouraged.

The Premenstrual Symptoms Screening Tool revised for adolescents (PSST-A): prevalence of severe PMS and premenstrual dysphoric disorder in adolescents.

The Premenstrual Symptoms Screening Tool was modified for use in adolescents and piloted in 578 girls at three international sites. Nearly one third (29.6%) reported experiencing severe PMS or PMDD, with irritability being the most commonly reported symptom. Rates of menstrual-related pain were high, particularly in those with severe PMS or PMDD. Severe PMS and PMDD present with similar rates and symptoms in adolescents as in adults, and the Premenstrual Symptoms Screening Tool modified for adolescents is a fast, reliable tool to screen for these syndromes in adolescents.

The rapid effects of estrogen: a mini-review.

Estrogen is regulated through two intracellular receptors, estrogen receptor alpha and estrogen receptor beta, through a classic nuclear-initiated response. Recently, estrogen has also been shown to act more rapidly and it is proposed that these fast effects may be the consequence of membrane localized estrogen receptors that act through the second messengers. Although the identification of these receptors remains to be elucidated, the possible role that they play in female-specific mood disorders is of particular interest, especially in times of major hormonal fluctuation. The purpose of this mini-review is to outline the recent literature regarding the rapid effects of estrogen, to explore the intracellular signaling pathways that may be involved in this regulation as well as the connection between estrogen and serotonin neurotransmission and finally, to look into the antidepressant role that estrogen may have, with particular emphasis on female-specific mood disorders.

Omega-3 supplements in pregnancy: are we too late to identify the possible benefits?

OBJECTIVE: Postpartum depression (PPD) is a common and recurring illness. Most women who experience PPD do not seek professional help; for those who do, the available treatment options are not supported by extensive research evidence. Several lines of research have linked omega-3 fatty acids (omega-3) supplementation with a reduced risk of PPD. Although it has been suggested that women in the perinatal period consume sufficient omega-3 to potentially prevent PPD, there is a lack of definitive research evidence. This pilot study surveyed pregnant women's current use of omega-3, multivitamin, and other supplements, as well as their attitudes toward omega-3 research during pregnancy, to assess the feasibility of pregnant women's participation in a large randomized controlled trial evaluating omega-3 supplementation. METHODS: Women attending prenatal clinics over a three-week period were invited to participate in a survey. The survey contained an information letter that was followed by a brief questionnaire assessing the use of nutritional supplements and opinions regarding the likelihood of participating in a clinical trial during pregnancy. RESULTS: Of the 176 women who completed the survey, six women were in the first trimester of pregnancy, 82 were in the second trimester, and 87 were in the third trimester. One hundred fifty-nine respondents (90.3%) reported taking a multivitamin supplement but none were taking a supplement that contained omega-3; only 20 (11.4%) were taking omega-3. Seventy-eight women (44.4%) responded that they would participate in a clinical study evaluating the effects of fish oil on their health. CONCLUSION: The results of our study indicate that many pregnant women take prenatal multivitamins and nutritional supplements, that there are currently few pregnant women attending clinics at our hospitals who are supplementing with omega-3, and that pregnant women would be willing to participate in a clinical trial evaluating the effects of omega-3.

New women-specific diagnostic modules: the Composite International Diagnostic Interview for Women (CIDI-VENUS).

The World Health Organization-Composite International Diagnostic Interview (WHO-CIDI) is a highly structured interview for the assessment of mental disorders, based on the definitions and criteria of the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Over the past decade it has become evident that the CIDI does not sufficiently address the assessment needs of women. Women are affected by most mental disorders, particularly mood and anxiety disorders, approximately twice as frequently as men. Women-specific disorders, such as Premenstrual Syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), psychiatric disorders during pregnancy and postpartum as well as during the perimenopause, menopause and beyond are not addressed by the standard CIDI diagnostic modules. In addition, the CIDI in its current form does not address the potential effect that female reproductive milestones may have on diagnosis, treatment and prevention of mental disorders in women. Our aim was to develop a new women specific platform (CIDI-VENUS; CIDI-V) to be embedded in the existing CIDI that will address the above mentioned current deficiencies. Guided by a team of experts in the field of Women's Mental Health from Canada and Germany the following modules were developed: 1) A complete menstrual history and comprehensive contraceptive history with a link to the Premenstrual Symptoms Screening Tool (PSST). 2) A complete perinatal history of pregnancies, miscarriages, terminations, still births, death of a child, with details of current pregnancy including gestation and expected date of confinement, labour history and breastfeeding, history of tobacco, alcohol, and other substance use including prescription drugs during pregnancy and postpartum, a section on specific phobias and on recurrent obsessive/compulsive thoughts/behaviours (OCD) related to the baby with a link to the Perinatal Obsessive-Compulsive Scale (POCS), as well as a link to the Edinburgh Postnatal Depression Scale (EPDS). 3). A detailed history of use of hormone therapy (e.g. pills, patches, implants, etc.) with a focus on (peri-) menopausal women, differentiating between physical and psychological symptoms with a link to the Menopause Visual Analogue Scales (M-VAS) and to the Greene Climacteric Scale. 4) An iterative module concluding each CIDI section to specify the course of mental disorders during the reproductive stages and menopausal transition. While retaining core diagnostic sections and diagnostic algorithms, the CIDI-V is enriched by women-specific diagnostic modules, providing a wealth of clinically relevant information about women's mental health, not available anywhere else in our current psychiatric diagnostic instruments.

The effect of depression on heart rate variability during pregnancy. A naturalistic study.

Depression during pregnancy has been associated with a number of adverse outcomes, but the underlying physiological mechanisms involved remain unclear. The purpose of this study was to examine the effects of maternal depression during pregnancy on the autonomic modulation of heart rate, in a naturalistic setting. Eighty-one pregnant women were studied between 25 and 31 weeks of gestation and were identified as either Depressed (n = 46), or healthy, Control (n = 35), based on depression scores and lifetime psychiatric history. Subjects wore a 24-h Holter recorder to measure time-domain and frequency-domain of heart rate variability (HRV). Pregnant women in the Depressed Group had significantly reduced time-domain measures: standard deviation of all 24-h NN intervals (SDNN) and the standard deviation of the averages of NN intervals in all 5-min segments of the entire recording (SDANN) (P = 0.013, 0.016, respectively), as well as higher heart rates while asleep (P = 0.028), compared to Controls, after controlling for age, smoking, and antidepressant (AD) medication. The low frequency/high frequency (LF/HF) ratio during the sleeping hours was associated with higher depression scores (R = 0.24; P = 0.041). HRV measures improved in women taking AD medication. The autonomic nervous system may be affected in women experiencing depression during pregnancy, indicating a possible decreased parasympathetic (vagal) influence. Women taking AD medication showed some improvement in HRV measures. These data suggest that psychophysiological changes occur in women experiencing depression during pregnancy.