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To evaluate the association between maternal age, parity, gestational number (singleton vs twin), newborn gender and self-reported postpartum depressive symptoms (PDS) in a large multinational sample using survey data from a digital telephone application.Women using the Flo app answered a survey (available in 10 languages) from January 2018 to April 2020. A survey question asking about emotional state was used to determine the presence of PDS. Chi-squared statistics were used to compare groups. A weighted mean prevalence was calculated based upon the socioeconomic status and reproductive population of each country in 2020.Over a million women from 138 countries participated. Of all respondents, 9.4% endorsed PDS. The weighted mean prevalence of PDS was 11%. We found that PDS decreased with advancing age. First-time mothers reported higher rates of PDS. Twin births were associated with a higher symptom burden than singleton births and mothers of twins in the oldest age group reported the greatest burden. We did not find a clinically significant difference in rates of PDS between mothers of singleton girls and boys.To our knowledge, this study is the first to examine risk factors for postpartum symptoms using the same survey across a large international population. These results can further research and clinical aims to identify and treat maternal depression more effectively.Data was aggregated, thereby limiting analysis of individual associations. The survey was self-report and not diagnostic for postpartum depression. Generalizability of risks of postpartum depression should be approached with caution.

Recent research has implicated allopregnanolone (ALLO), a neuroactive steroid and metabolite of progesterone, in perinatal mood and anxiety symptoms. We sought to add to the limited literature examining ALLO and mood and anxiety at multiple time points across the peripartum. We measured mood and anxiety symptoms and ALLO levels by ELISA at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in N = 73 women with prior histories of mood and/or anxiety disorders and N = 38 healthy controls. Analytic methods included multivariate and logistic regressions with linear mixed effect models. Among all participants (N = 111), higher ALLO levels at W6 were associated with higher depression and anxiety scores: each one unit increase in log ALLO at W6 was associated with a 2.54 point increase on the Edinburgh Postnatal Depression Scale (EPDS) (95% CI: 0.73 to 4.33) and an 8.0 point increase on the Perinatal Anxiety Screening Scale (PASS) (95% CI: 3.82 to 12.6). In addition, the nature of the relationship between log ALLO level and psychological measures changed across time; from T2 to W6 for EPDS, β = 3.73 (95% CI:1.16, 6.30), p = 0.0045; for PASS β = 9.78 (95% CI:3.77, 15.79), p = 0.0014); from T3 to W6, for (EPDS, β = 2.52 (95% CI:0.08, 4.96), p = 0.043; for PASS β = 7.33 (95% CI:1.63, 13.02), p = 0.018). The relationship of log ALLO to mood and anxiety symptoms was the same among women with and without psychiatric histories. Our exploratory findings indicate that the relationship between ALLO and mood and anxiety symptoms may change across the peripartum.

Perinatal depression affects 10% to 20% of women in the United States during pregnancy, the postpartum period, or both, but it can be difficult to recognize. Identifying and treating this problem can reduce the alarming number of suicides among depressed perinatal women and the possible adverse effects of untreated maternal depression on their child's cognitive and behavioral development. In this review, we discuss the latest developments in screening, treatment, and prevention methods.

Premenstrual symptoms, including physical and mood symptoms, affect a large proportion of women worldwide. Data on premenstrual symptoms across nations and age groups is limited. In the present study, we leveraged a large international dataset to explore patterns in premenstrual symptom frequency with age. A survey was administered to users of the Flo mobile application (app), aged 18 to 55. The survey queried app users about a range of premenstrual symptoms. Respondents were asked whether they experienced each symptom every menstrual cycle, some cycles, or never. Age was also captured and categorized as 18–27, 28–37, 38–47, 48–55. Data was summarized and Pearson’s chi square test for count data assessed differences in symptom frequency by age group. A sample of 238,114 app users from 140 countries responded to the survey. The most common symptoms reported were food cravings (85.28%), mood swings or anxiety (64.18%), and fatigue (57.3%). Absentmindedness, low libido, sleep changes, gastrointestinal symptoms, weight gain, headaches, sweating or hot flashes, fatigue, hair changes, rashes, and swelling were significantly more frequent with increasing age (p’s

ObjectiveEarly life stress (ELS) increases the risk for postpartum depression (PPD). The patients with depression who experienced ELS tend to be treatment refractory. However, the mechanism by which ELS is involved in the pathophysiology of PPD remains unclear. We investigated the longitudinal effects of ELS on the hypothalamic-pituitary-adrenal (HPA) axis and behaviors in the postpartum period through mouse and human studies.MethodsBehavioral tests (tail suspension, forced swim, and three-chamber social interaction tests) and measurement of plasma hormone levels were administered at postpartum in female mice with or without exposure to social isolation during late adolescence. Effects of a glucocorticoid receptor antagonist, a serotonin reuptake inhibitor, or a GABAA receptor modulator on their behaviors were examined at one week postpartum. Human plasma cortisol levels from women with ELS were also examined at second and third trimesters as well as two and six weeks postpartum.ResultsWe observed that adolescent social isolation caused an aberrantly sustained elevation of glucocorticoids via dysregulation of the HPA axis, leading to long-lasting postpartum behavioral changes in female mice. The postpartum behavioral changes elicited by this ELS were not ameliorated by the medicines currently used for PPD treatment. However, a post-delivery treatment with a glucocorticoid receptor antagonist effectively ameliorated the behavioral changes in mice. We also demonstrated a significant impact of ELS on the HPA axis dysregulation and PPD in women.ConclusionsWe provide experimental evidence that suggest a mechanism-driven therapeutic strategy (repurposing a GR antagonist) for at least some cases of treatment refractory PPD.

STUDY OBJECTIVES: Postpartum depression (PPD) occurs in 15% to 20% of mothers worldwide and is associated with adverse outcomes for mother and child. Prior research has established a relationship between concurrent sleep quality and PPD. We conducted a secondary analysis in 45 women with mood disorders to study overall sleep quality (and individual components of sleep), measured in the early postpartum period, as a predictor of subsequent PPD. METHODS: We measured sleep quality using the Pittsburgh Sleep Quality Index (PSQI; subscale and total scores) at 1 month postpartum (and during the third trimester). We measured depressive symptoms using the Inventory of Depressive Symptoms, Self-Report (IDS-SR) at 3 months postpartum. We used bivariate and multivariate linear regression models to study the association between PSQI and IDS scores. RESULTS: We found that higher global PSQI scores as well as higher component scores for self-reported sleep quality, sleep latency, sleep efficiency, sleep medication usage, and daytime dysfunction, measured 1 month postpartum, were associated with increased IDS scores (at 3 months postpartum (P = .01, .01, .01, .003, < .001, respectively). We did not find an association between poor sleep quality in the third trimester and PPD. CONCLUSIONS: Poor sleep quality in the early postpartum period independently predicts development of later PPD. This is clinically significant and highlights the importance of sleep interventions as an immediate postpartum therapeutic tool. CITATION: McEvoy KM, Rayapati D, Washington Cole KO, Erdly C, Payne JL, Osborne LM. Poor postpartum sleep quality predicts subsequent postpartum depressive symptoms in a high-risk sample. J Clin Sleep Med. 2019;15(9):1303–1310.

Purpose of Review To provide an overview of existing studies on alterations in gonadal and neuroactive steroids (NASs) and mood symptoms among women with polycystic ovary syndrome (PCOS). Recent Findings Recent studies have demonstrated a previously underappreciated association between PCOS and comorbid depression and anxiety. However, most studies on affective symptoms among women with PCOS have been cross-sectional, limiting our knowledge about fluctuations in symptoms over the menstrual cycle and reproductive lifespan for women with PCOS, as well as the potential interplay between NAS alterations and mood symptoms. Changes in the NAS allopregnanolone (ALLO) have been implicated in several reproductive-related psychiatric disorders (e.g., premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD)) as well as in normal reproductive functioning, warranting further investigation for its potential role in the psychiatric symptoms observed in women with PCOS. Summary Prospective studies evaluating associations between psychiatric symptoms and NAS are needed to elucidate the biological causes of the increased rates of psychiatric symptoms among women with PCOS and inform clinical treatment. ALLO, with its role in normal reproductive function, menstrual dysregulation among women with PCOS, and reproductive-related psychiatric conditions, makes it a particularly intriguing candidate for future investigation.

Objective Peripartum depression is a leading contributor to peripartum morbidity and mortality. Despite the evidence for relative safety, many patients and providers remain reluctant to use or modify psychotropics in the peripartum period. We hypothesized that depressed women in the peripartum period taking psychiatric medications would not experience dose adjustments. Methods Women with a prior history of either Major Depressive Disorder or Bipolar Affective Disorder were followed through pregnancy and the postpartum period (N = 229). Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS), with a score ≥ 13 indicating likely depression. Data analysis included descriptive statistics, chi-square tests, and logistic regression. Results Antepartum depression was more common than postpartum depression (PPD; 29% vs. 20%); 38% of women with antepartum depression also had PPD. Regression analysis revealed that, although depressed women in pregnancy were not more likely to have a dose adjustment than nondepressed women (OR: 1.9, 95% CI: 0.8-4.6), depressed women in the postpartum were more likely to receive a medication change than nondepressed women (OR: 6.3, 95% CI: 2.0-20.4). Conclusions In a naturalistic study, more medication adjustments for depression occurred in the postpartum than in pregnancy. This may indicate that antepartum depression is undertreated.

Postpartum depression (PPD) is a serious and common complication of childbirth that can have deleterious effects not only on the mother but on the cognitive and behavioral development of exposed children. Brexanolone is a novel, soluble synthetic formulation of the natural hormone allopregnanolone and acts as a positive allosteric modulator of the gamma-aminobutyric acid A receptor (GABAA). Allopregnanolone levels dramatically decrease during the postpartum time-period and some studies indicate lower serum levels of allopregnanolone during pregnancy in women that go on to develop PPD.Areas covered: The author provides an overview of brexanolone as a treatment option for PPD including coverage of its pharmacokinetics, efficacy, safety, and tolerability. Furthermore, the author gives her expert perspectives on its use and its standing in the treatment armamentarium moving forward.Expert opinion: Brexanolone represents a breakthrough for psychiatry due to its novel mechanism of action, its rapid onset of action, and its sustained effects without continued administration. It is appropriate for use in women with moderate to severe PPD. Experience with the medication and further research is needed to clarify whether the current recommended dosing regimen is required for efficacy.

Active peripartum psychiatric illness is associated with adverse outcomes for exposed pregnancies/children. Likely due to high rates of obesity, pregnant women with psychiatric illness also have higher rates of preeclampsia, cesarean section, and gestational diabetes. Postpartum depression is associated with lower IQ, slower language development, and behavioral problems in exposed children. Discontinuing psychiatric medications for pregnancy increases risk for relapse significantly, and the postpartum time period is high risk for developing psychiatric illness. Obstetricians-gynecologists are front-line providers for psychiatric care of women during peripartum. This article provides a framework and knowledge base for management of psychiatric illness during peripartum.

Purpose: Pathological worry is a major feature of anxiety in the peripartum, and we sought to examine the factor structure, validity, and reliability in the peripartum of a scale used to measure worry in the general population (the Penn State Worry Questionnaire, PSWQ). Materials and Methods: Pregnant/postpartum women (N = 295) were followed at up to six visits, which included completion of the PSWQ and other psychological scales. Principal components analysis, descriptive statistics, paired t-tests, chi-square tests, and mixed linear regression models were used to evaluate scale reliability and validity. Results: Most participants (63%) reported a history of a mood disorder, 40% an anxiety disorder, and 18% both. Mean PSWQ score at entry was 47.19 (of a possible 80). PSWQ scores were positively correlated with conceptually related measures (correlations 0.55–0.76, all p

BACKGROUND. Anxiety in pregnancy is one of the strongest risk factors for postpartum depression (PPD), and high worry is a hallmark of many anxiety disorders. We sought to determine whether the Penn State Worry Questionnaire (PSWQ), designed for the general population, could identify high worry in pregnancy and predict the development of PPD symptoms (PPDS). METHODS. We followed women (N=295) with and without mood and anxiety disorders across pregnancy and up to 6 months postpartum. Diagnoses were confirmed by SCID and by an experienced perinatal psychiatrist, and we administered the PSWQ and the Edinburgh Postnatal Depression Scale (EPDS) at up to 6 time points. We determined the trajectory of worry across time and its relationship to PPDS. RESULTS. Women with a history or current diagnosis of major depressive disorder (MDD) or generalized anxiety disorder (GAD) were more likely to experience high antenatal worry (defined as PSWQ >60), p < 0.004 for MDD and

Epigenetic changes in DNA methylation of genes alter gene transcription and are subject to environmental influences including exposure to hormones, stress, and other factors. This chapter describes epigenetic studies focused on postpartum depression. Two groups of studies are discussed including research examining a role for estrogen-influenced genes as well as research on epigenetic modification of the oxytocin receptor gene. Future work in this area should carefully define the phenotypes of participants including the presence or absence of preexisting mood disorders and the timing of onset of symptoms. Epigenetic studies of postpartum depression are an exciting area marrying the influence of biology (genetics) with the environment (hormone exposure).

Psychiatric illness during and immediately after pregnancy is common and potentially life-threatening. The proper management of psychiatric disorders during the peripartum time period remains controversial, though this is likely secondary to the stigma associated with psychiatric illness rather than a lack of data. Much of the early literature exploring the relationship between in utero psychiatric medication exposure and infant outcomes was flawed by inappropriate control populations, small sample sizes, and a lack of controls for confounds including psychiatric illness itself and associated health risk factors and behaviors. More recent studies are generally better designed to study whether infant outcomes are influenced by in utero medication exposure or by exposure to maternal psychiatric illness or both. The preponderance of the literature is reassuring regarding the safety of the use of most (not all) psychiatric medications during pregnancy and lactation. The preponderance of the literature also supports that unfavorable infant outcomes are associated with exposure to maternal mental illness. This chapter attempts to summarize what is currently known about the safety of psychiatric medications during pregnancy and lactation and, in addition, describes a clinical approach to designing a treatment plan for individual patients during this critical time for both mother and child.

Familial, genome-wide linkage and association studies, and candidate gene studies, most conducted in the past 10 years, have examined the genetic etiology of postpartum depression (PPD). The most commonly studied genes include genes that have been implicated in other mood disorders, particularly major depression though some like estrogen receptor 1 have been studied based on a theoretical involvement in PPD itself. Evidence is strong for the genetic basis for PPD with approximately a 40% heritability. The heritability is thought to be a mixture of genetic risks for other types of mood disorders and genetic risks that are unique to PPD. Positive associations have been found in family studies and in several genes associated with major depression as well as genes involved in estrogen signaling but only when PPD onset is defined shortly after delivery. Our findings underscore the need for additional studies with larger samples, as well as the crucial importance of timing in the definition of PPD for genetic studies.

We began this project with the idea that this book would serve not only as a roadmap for where research on postpartum mood and anxiety disorders has been but also as a guide for where research in this critical area needs to go. After reading and editing all the chapters in this volume, we realized that a number of themes have emerged. This chapter summarizes these themes and discusses future directions of research.

This article is a comment on Vaswani, Karter, Cosgrove, Peters, and Brodt's (2018) article “Depression Screening During Pregnancy and the Postpartum Period: Enhancing Informed Consent Practices.” D...

Objectives The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). Study Design and Setting Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]). Results We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains “pain intensity” (gabapentin) and “depression” (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = −0.45; 95% confidence interval [CI]: −0.63 to −0.27) to ineffective (SMD = −0.06; 95% CI: −0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = −0.55; 95% CI: −0.85 to −0.25) to a small effect (SMD = −0.26; 95% CI: −0.41 to −0.1). Conclusions Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.

Current evidence is mixed on the role of progesterone and its metabolites in perinatal mood and anxiety disorders. We measured second and third trimester (T2 and T3) progesterone (PROG) and allopregnanolone (ALLO) levels by ELISA and postpartum depression (PPD) by clinician interview (DSM-IV criteria) in 60 pregnant women with a prior diagnosis of a mood disorder. Methods included multivariate and logistic regression with general linear mixed effect models. We found that, after adjustment, every additional ng/mL of T2 ALLO resulted in a 63% (95% CI 13% to 84%, p = 0.022) reduction in the risk of developing PPD. Our findings extend previous work connecting ALLO and depression within pregnancy, and indicate that the relationship between pregnancy ALLO and PPD is worth further exploration in a larger sample.

AIMS: We examined whether problem-solving and diabetes self-management behaviors differ by depression diagnosis - major depressive disorder (MDD) and minor depressive disorder (MinDD) - in adults with Type 2 diabetes (T2DM). METHODS: We screened a clinical sample of 702 adults with T2DM for depression, identified 52 positive and a sample of 51 negative individuals, and performed a structured diagnostic psychiatric interview. MDD (n = 24), MinDD (n = 17), and no depression (n = 62) were diagnosed using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria. Health Problem-Solving Scale (HPSS) and Summary of Diabetes Self-Care Activities (SDSCA) questionnaires determined problem-solving and T2DM self-management skills, respectively. We compared HPSS and SDSCA scores by depression diagnosis, adjusting for age, sex, race, and diabetes duration, using linear regression. RESULTS: Total HPSS scores for MDD (β = −4.38; p < 0.001) and MinDD (β = −2.77; p < 0.01) were lower than no depression. Total SDSCA score for MDD (β = −10.1; p < 0.01) was lower than for no depression, and was partially explained by total HPSS. CONCLUSION: MinDD and MDD individuals with T2DM have impaired problem-solving ability. MDD individuals had impaired diabetes self-management, partially explained by impaired problem-solving. Future studies should assess problem-solving therapy to treat T2DM and MinDD and integrated problem-solving with diabetes self-management for those with T2DM and MDD.

We sought to replicate and expand upon previous work demonstrating antenatal TTC9B and HP1BP3 gene DNA methylation is prospectively predictive of postpartum depression (PPD) with ~80% accuracy. In a preterm birth study from Emory, Illumina MethylEPIC microarray derived 1st but not 3rd trimester biomarker models predicted 3rd trimester Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 13 with an AUC=0.8 (95% CI: 0.63-0.8). Bisulfite pyrosequencing derived biomarker methylation was generated using bisulfite pyrosequencing across all trimesters in a pregnancy cohort at UC Irvine and in 3rd trimester from an independent Johns Hopkins pregnancy cohort. A support vector machine model incorporating 3rd trimester EPDS scores, TTC9B, and HP1BP3 methylation status predicted 4 week to 6 week postpartum EPDS ≥ 13 from 3rd trimester blood in the UC Irvine cohort (AUC=0.78, 95% CI: 0.64-0.78) and from the Johns Hopkins cohort (AUC=0.84, 95% CI: 0.72-0.97), both independent of previous psychiatric diagnosis. Technical replicate predictions in a subset of the Johns Hopkins cohort exhibited strong cross experiment correlation. This study confirms the PPD prediction model has the potential to be developed into a clinical tool enabling the identification of pregnant women at future risk of PPD who may benefit from clinical intervention.

What is ‘Reproductive Psychiatry’ and why is it a topic worth knowing about, researching, and teaching about? How is ‘Reproductive Psychiatry’ different from ‘Women’s Mental Health?’ Those of us in...

The use of psychotropic drugs during pregnancy and breastfeeding remains a controversial topic. There are several reasons for the controversy, ranging from the misperception that pregnancy is protective against mental illness, to the notion that women should be "pure" during pregnancy and avoid all extraneous substance use, and finally, to the stigma and misunderstanding of psychiatric illness and underestimation of how serious it can be. Fortunately, the currently available data are reassuring for most psychiatric medications-properly controlled studies indicate little to no risk for most (but not all) psychiatric medications.

Objectives We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials. Study Design and Setting We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight. Results Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information. Conclusion Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Maternal depression is associated with an array of poor child health outcomes, and low-income women face many barriers to accessing treatment. In this pilot study, we assessed treatment engagement in a maternal mental health clinic staffed by a case manager and psychiatrist in an urban pediatric practice. We also examined factors associated with engagement as well as child health outcomes and health care use. Nearly half of the women enrolled attended at least 4 sessions with a psychiatrist in 6 months. Text messaging with the case manager was associated with a greater compliance with psychiatrist sessions. Comparing index children with their siblings prior to enrollment, a higher percentage had immunizations up to date at 1 year of age (82% vs 43%, P = .01), and well-child visit compliance trended toward significance (65% vs 35%, P = .06). The pediatric setting holds promise as an innovative venue to deliver maternal mental health care.

We thank Dr. Laflamme for her insightful letter regarding our article. We wholeheartedly agree that earlier contact with obstetric-care providers, such as during “fourth trimester” contact, is ideal. We also encourage all obstetric providers to screen at least at the 6-week in-person postpartum

Postpartum depression is a serious illness affecting up to 15% of women worldwide after childbirth, and our understanding of its biology is limited. Postpartum anxiety is perhaps more prevalent and less understood. Prior studies indicate that allopregnanolone, a metabolite of progesterone, may play a role in reproductive mood disorders, including postpartum depression, but the exact nature of that role is unclear. Our own prior study in a group of psychiatrically ill women found that low allopregnanolone in the second trimester predicted the development of postpartum depression. In the present study, in both healthy and mood- and anxiety-disordered women who remained well throughout the perinatal period, we found that second trimester allopregnanolone predicted postpartum anxiety symptoms, with a similar trend toward the prediction of postpartum depressive symptoms (though without statistical significance). Both concurrent sleep and prior histories of mood and anxiety disorders contributed to the variance in mood and anxiety scores at 6 weeks postpartum. These findings confirm the importance of pregnancy allopregnanolone in postpartum psychiatric symptoms and point to future directions that may determine other important contributing factors.

PURPOSE OF REVIEW. The purpose of this review is to provide a theoretical explanation and a review of the recent literature concerning the role of neuroactive steroids in perinatal depression, and to use this information to suggest future directions of research. RECENT FINDINGS. The bulk of the evidence on neuroactive steroids in perinatal depression concerns allopregnanolone. Recent studies have been mixed, with some studies finding a direct correlation between lower levels of allopregnanolone and increased depressive symptoms but other studies finding no relationship. Evidence concerning other neuroactive steroids and perinatal depression is sparse. SUMMARY. Additional research is needed with larger sample sizes and better characterization across the perinatal period (rather than cross-sectionally). Because some studies point to a lag between neuroactive steroid dysregulation and subsequent symptoms, future research should consider interactions with other systems (inflammatory or HPA) or other aspects of neuroactive steroids (such as synthetic enzymes or receptor plasticity).

This review aims to summarize the diverse proposed pathophysiological mechanisms contributing to postpartum depression, highlighting both clinical and basic science research findings. The risk factors for developing postpartum depression are discussed, which may provide insight into potential neurobiological underpinnings. The evidence supporting a role for neuroendocrine changes, neuroinflammation, neurotransmitter alterations, circuit dysfunction, and the involvement of genetics and epigenetics in the pathophysiology of postpartum depression are discussed. This review integrates clinical and preclinical findings and highlights the diversity in the patient population, in which numerous pathophysiological changes may contribute to this disorder. Finally, we attempt to integrate these findings to understand how diverse neurobiological changes may contribute to a common pathological phenotype. This review is meant to serve as a comprehensive resource reviewing the proposed pathophysiological mechanisms underlying postpartum depression.

Background We used various methods for identifying and prioritizing patient-centered outcomes (PCOs) for comparative effectiveness research (CER). Methods We considered potential PCOs (“benefits” and “harms”) related to (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. Part 1 (April 2014 to March 2015): we searched for PCO research and core outcome sets (COSs). We conducted electronic searches of bibliographic databases and key websites and examined FDA prescribing information and reports of clinical trials and systematic reviews. We asked patient and clinician co-investigators to identify PCOs. Part 2 (not part of our original study protocol): in 2015, we surveyed members of The TMJ Association, Ltd., a patient group associated with temporomandibular disorders (4130 invitations sent). Participants prioritized (1) the importance of six potential benefits and (2) 21 potential harms selected by the investigators in part 1, using stated preference methods. We calculated descriptive statistics. Results In part 1, we identified a COS for pain, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. The COS identified several important benefits, but it lacked specific recommendations about which potential harms to include in CER. We did not identify a COS for bipolar depression. Research reports, prescribing information, and patient co-investigators helped identify but not prioritize outcomes. We abandoned our electronic search for PCO research because we found it would be resource-intensive and yield few relevant reports. In part 2, surveying patients was useful for prioritizing PCOs. Members of The TMJ Association, Ltd., completed the survey (N = 746) and successfully prioritized both benefits and harms. Participants did not identify many benefits other than those we identified in part 1; several participants identified additional harms. Conclusions These exploratory results could inform future research about identifying and prioritizing PCOs. We found that stakeholder co-investigators and research reports contributed to identifying PCOs; surveying a patient group contributed to prioritizing PCOs. Prioritizing potential harms was particularly challenging because there are many more potential harms than potential benefits. Methods for identifying and prioritizing potential benefits for CER might not be appropriate for harms. Further research is needed to determine the generalizability of these results. Electronic supplementary material The online version of this article (10.1186/s40814-018-0284-6) contains supplementary material, which is available to authorized users.

Background Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial. Methods We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., “clinical study reports”) and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources. Systematic review registration CRD42015014037, CRD42015014038