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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.

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.

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.

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.

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.

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.

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

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.

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.

Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24–32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18–36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value

The purpose of this study is to review and summarize the literature exploring the genetic basis for premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD). There is more evidence for a genetic basis for PPD than for PMDD, but only when PPD is defined as beginning in the immediate postpartum time period. Familial, genome-wide linkage and association studies, and candidate gene studies, most in the past 10 years, have examined the genetic etiology of reproductive affective disorders, including PMDD and PPD. The most commonly studied genes include SERT, COMT, MAOA, BDNF, and ESR1 and 2. This qualitative review of the recent literature finds limited evidence so far for the genetic basis for PMDD, with both familial and candidate gene studies having negative or conflicting results. Evidence is stronger for the genetic basis for PPD, with positive associations 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 shortly after delivery. Epigenetic biomarkers on genes responsive to estrogen have also been found to predict PPD. 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.

BackgroundUniversal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.MethodOrdinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.ResultsEducation, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).ConclusionsInvestigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Objectives The aim of this study was to screen for depression and anxiety and to assess well-being among women diagnosed with gynecologic malignancies, identify factors associated with elevated depressive or anxiety symptoms, and further characterize the needs of those with elevated anxiety or depressive symptoms. Methods/Materials Women presenting for gynecologic cancer at an academic center during the course of 10 months were offered screening for depressive and anxiety symptoms. Patients were screened with the Primary Care Evaluation of Mental Disorders’ Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7. The Functional Assessment of Cancer Therapy-General assessed well-being. Demographics, psychiatric history, and components about the cancer and treatment were collected. Those who screened positive with scores of 10 or higher on the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 were offered a meeting with the study psychiatrist for further evaluation both with the Structured Clinical Interview for Diagnosis as well as with an interview to discuss their experiences and to assess their desired needs. Results When family and social well-being was added to the logistic regression model, higher family and social well-being was the strongest factor associated with lower amounts of anxiety (odds ratio, 0.10; P = 0.001 for a cutoff of 10; odds ratio, 0.21; P = 0.012 for a cutoff of 8). Less than 30% who screened positive met with the study psychiatrist and were not receiving optimal treatment. Conclusions Given that low family and social well-being and elevated anxiety symptoms were so highly correlated, those with anxiety symptoms would most benefit from social interventions. However, this study also found that patients with elevated depressive or anxiety symptoms were difficult to engage with a psychiatric provider. We need partnership between psychiatry and gynecology oncology to identify those with elevated depressive and anxiety symptoms and develop better ways to provide psychosocial supports.

We sought to determine clinical predictors of postpartum depression (PPD), including the role of medication, in a sample of women followed prospectively during and after pregnancy. Women with a history of mood disorder were recruited and evaluated during each trimester and 1 week, 1 month, and 3 months postpartum. DSM-IV criteria for a major depressive episode were assessed by a psychiatric interview at each time point. Sixty-three women with major depression and 30 women with bipolar disorder entered the study and 75.4 % met DSM-IV criteria for a MDE during pregnancy, postpartum, or both. We modeled depression in a given time period (second trimester, third trimester, or 1 month postpartum) as a function of medication use during the preceding period (first, second, or third trimester). The odds of being depressed for those who did not use medication in the previous period was approximately 2.8 times that of those who used medication (OR 2.79, 95 % CI 1.38-5.66, p = 0.0048). Of 38 subjects who were psychiatrically well during the third trimester, 39.5 % (N = 15) met the criteria for a MDE by 4 weeks postpartum. In women who developed PPD, there was a high rate of a family history of PPD (53.3 %) compared to women who did not develop PPD (11.8 %, p = 0.02). While the use of psychiatric medications during pregnancy reduced the odds of being depressed overall, the use of psychiatric medications during pregnancy may not protect against PPD in women at high risk, particularly those with a family history of PPD.

The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new “Depressive disorders” section, which is separate from “Bipolar disorders”, marking a division in what had been known as “Mood disorders”. A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorder category is intended to encompass both dysthymia and chronic depression, but its relationship to MDD is ambiguous with conflicting statements on whether the two diagnoses should be concurrent if both sets of criteria are fulfilled. Clarification is also needed on whether MDD can be concurrent with the new broad “other specified bipolar and related disorders”. New specifiers of MDD “with anxious distress” and “with mixed features” allow characterization of additional symptoms. The specifier “with perinatal onset” expands on the DSM-IV “postnatal onset” to include onset during pregnancy. We review the changes in MDD definition, provide guidance on their implementation and discuss their implications for clinical practice and research.

The management of mood disorders during pregnancy is complex due to risks associated with medication use and risks associated with untreated depression. Antidepressant use during pregnancy is an exposure for the unborn child, and it currently remains unclear what long-term repercussions there might be from this exposure, though available data are reassuring. On the other hand, there are risks for both the mother and child of untreated depression during pregnancy. There is a real need for research into nonpharmacological strategies for the prevention of relapse of mood disorders in pregnant women who are off medications. We have reviewed a number of potential candidate interventions including psychotherapies, exercise, light box therapy (LBT), repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), holistic strategies, and nutritional and herbal supplements. Currently there is a lack of evidence supporting the use of such strategies in the prevention of depressive relapse during pregnancy, though most of these strategies have at least some support for their use in the treatment of a major depressive episode. Carefully conducted research using one or more of these strategies in women who want to discontinue antidepressants for pregnancy is sorely needed.

BACKGROUND: The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods.METHODS: Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19-40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the 10-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria (RDoC) functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes.FINDINGS: Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe.INTERPRETATION: Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression.FUNDING: Janssen Research & Development.

Objective To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes. Methods We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder. We estimated prevalence of MinD and MDD and derived 95% CIs. Results The crude prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9–9.2%), 9.6% (95% CI: 3.9–15.9%), and 13.9% (95% CI: 7.7–21.2%), respectively. The crude prevalence of current, past, and current or past MDD was slightly higher—5.0% (95% CI: 1.9–9.4%), 12.0% (95% CI: 6.1–19.5%), and 17.0% (95% CI: 10.1–24.8%), respectively. There was a high prevalence of coexisting anxiety disorders in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not significantly different in individuals with MinD or MDD compared to those without a depressive disorder. Conclusions MinD is comparably prevalent to MDD in patients with type 2 diabetes; both disorders are associated with concomitant anxiety disorders. MinD is not included in the DSM-5; however, our data support continuing to examine patients with chronic medical conditions for MinD.

The purpose of this review is to update readers on recent controversies and findings on the underlying biology and clinical management of peripartum depression.Topics discussed include the discovery and replication of two epigenetic biomarkers of peripartum depression, two well controlled studies that do NOT find associations between in utero antidepressant exposure and cardiac defects and persistent pulmonary hypertension of the newborn and ongoing controversy on whether antidepressant use during pregnancy prevents peripartum depression and whether or not hormonal treatments have a place in the management of postpartum depression.Peripartum depression, or depression during and/or immediately following pregnancy is a unique psychiatric illness that not only may have unique biological underpinnings but demands unique and thoughtful approaches to management due to the developing neonate. A number of controversies exist in this area ranging from the recent terminology change in psychiatry's Diagnostic and Statistical Manual from "postpartum" to "peripartum" depression, to the safety of antidepressant use during pregnancy, to whether or not antidepressants prevent or decrease peripartum depression. Research in this area is growing and a number of exciting developments have occurred including the identification of two epigenetic biomarkers of peripartum depression that may eventually lead to early identification and intervention, the potential for hormonal treatments and the recommendation for and early institution of universal screening for peripartum depression. These topics are explored and put into context from a clinical management perspective.

The correct title of the article [1] should be “Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol”.

We sought to evaluate the prevalence rate and factors associated with post adoption depression. One hundred and twelve adoptive mothers of infants under 12 months of age were recruited from local and national adoption organizations. A modified Edinburgh Postnatal Depression Scale (EPDS) and a questionnaire collecting medical and psychiatric history, perceived stress, and demographics were administered retrospectively. The rates of significant depressive symptoms (defined as EPDS >or=12) were calculated at three time points post adoption, and associations with specific clinical variables (personal or family psychiatric history, stress, and adjustment difficulty) were assessed. Eighty-six mothers were included. Rates of significant depressive symptoms (EPDS >or=12) were found in 27.9% of subjects at 0-4 weeks, 25.6% at 5-12 weeks, and 12.8% at 13-52 weeks post adoption. Significant depressive symptoms were not associated with personal or family psychiatric history but were associated with stress (p = 0.0011) and adjustment difficulties (p = 0.042) post adoption. Significant depressive symptoms were relatively common in adoptive mothers within the first year after adoption and were associated with environmental stress. Prospective studies are needed to confirm the existence of post adoption depression and the factors associated with it.

Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline ZLR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.

Payne JL, MacKinnon DF, Mondimore FM, McInnis MG, Schweizer B,Zamoiski RB, McMahon FJ, Nurnberger Jr JI, Rice JP, Scheftner W,Coryell W, Berrettini WH, Kelsoe JR, Byerley W, Gershon ES,DePaulo Jr JR, Potash JB. Familial aggregation of postpartum moodsymptoms in bipolar disorder pedigrees.Bipolar Disord 2008: 10: 38–44. a Blackwell Munksgaard, 2008Objectives: We sought to determine if postpartum mood symptomsand depressive episodes exhibit familial aggregation in bipolar Ipedigrees.Methods: A total of 1,130 women were interviewed with the DiagnosticInterview for Genetic Studies as part of the National Institute of MentalHealth (NIMH) Genetics Initiative Bipolar Disorder CollaborativeStudy and were asked whether they had ever experienced moodsymptoms within four weeks postpartum. Women were also askedwhether either of two major depressive episodes described in detailoccurred postpartum. We examined the odds of postpartum moodsymptoms in female siblings, who had previously been pregnant and hada diagnosis of bipolar I, bipolar II, or schizoaffective (bipolar type)disorders (n ¼ 303), given one or more relatives with postpartum moodsymptoms.Results: The odds ratio for familial aggregation of postpartum moodsymptoms was 2.31 (p ¼ 0.011) in an Any Mood Symptoms analysis(n ¼ 304) and increased to 2.71 (p ¼ 0.005) when manic symptoms wereexcluded, though this was not significantly different from the Any MoodSymptoms analysis. We also examined familial aggregation ofpostpartum major depressive episodes; however, the number of subjectswas small.Conclusions: Limitations of the study include the retrospectiveinterview, the fact that the data were collected for other purposes and theinability to control for such factors as medication use. Taken togetherwith previous studies, these data provide support for the hypothesis thatthere may be a genetic basis for the trait of postpartum mood symptomsgenerally and postpartum depressive symptoms in particular in womenwith bipolar disorder. Genetic linkage and association studiesincorporating this trait are warranted.

Background Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively. Results Using a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures. Conclusions We conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0279-1) contains supplementary material, which is available to authorized users.

This chapter will discuss the issues of psychiatric management of bipolar disorder (BD) both during and after pregnancy. The risks and benefits of medication use during pregnancy will be discussed along with the risks of discontinuation of medications for pregnancy. Pharmacological treatments will be discussed in detail. The postpartum time period and its risks for depression, mania, and psychosis will be described, and recommendations for management during this critical time period will be detailed. Medication use during breastfeeding will also be discussed.

A 30-year-old woman, 6 weeks postpartum, is referred by her obstetrician for possible postpartum depression. The patient noted onset of symptoms 2 days after delivery of her son; describing the onset, she said she felt as if "a curtain descended upon" her. Her symptoms include low mood, tearfulness, decreased sleep and appetite, significant weight loss, and anhedonia. She feels she cannot care for her son properly and has intrusive thoughts that some unspecified harm may come to him. She adamantly denies thoughts of hurting herself or her son but worries constantly that "something bad will happen." At night, she feels restless and frequently checks that the baby is still breathing. Her concentration is poor, and she often does not shower or take care of household duties, but she does care for her son. On examination, the patient appears sad and anxious, with psychomotor retardation. She denies a previous psychiatric history. Her family history is notable for bipolar I disorder in a paternal uncle and a grandfather. She is breastfeeding. A 27-year-old woman with a history of recurrent major depression since age 18 presents for a consultation during her second trimester of pregnancy. The patient has a history of nonresponse to selective serotonin reuptake inhibitors (SSRIs) and has been hospitalized twice for severe depressive episodes. During the second hospitalization, at age 25, she required six ECT treatments. Since that time, she has been maintained with good results on 75 mg daily of nortriptyline. Her treating psychiatrist recommended that she continue taking the nortriptyline during the pregnancy, which she has done.

Background: We sought to determine the prevalence of, and association between, reproductive cycle-associated mood symptoms in women with affective disorders. We hypothesized that symptoms would correlate with each other across a woman's reproductive life span in both major depression (MDD) and bipolar I disorder (BP). Methods: 2412 women with, MDD or BP were asked standardized questions about mood symptoms prior to menstruation, within a month of childbirth and during perimenopause. Lifetime rates for each of these symptom types were determined and an odds ratio was calculated correlating each of the types with the others. Results: Of 2524 women with mood disorders, 67.7% reported premenstrual symptoms. Of those at risk, 20.9% reported postpartum symptoms and 26.4% reported perimenopausal symptoms. The rates did not differ between women with MDD and BP but were significantly different from women who were never ill. The symptoms were significantly correlated in women with MDD with odds ratios from 1.66 to 1.82, but were not in women with BP. Limitations: This is a secondary analysis of a sample that was collected for other purposes and is based upon retrospecitve reporting. Conclusions: Reproductive cycle-associated mood symptoms were commonly reported in women with mood disorders and did not differ based on diagnosis. In MDD, but not BP, the occurrence of these symptoms was trait-like as the presence of one predicted the occurrence of the others. Further prospective study is required to clarify the determinants of this trait.

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.

The oxytocin receptor ( OXTR ) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR . Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P = 0.014) with PPD in an intronic region in the OXTR located 4 bp proximal to an estrogen receptor (ER) binding region. Pyrosequencing confirmed moderate evidence for an interaction of CpGs in the region with childhood abuse status to mediate PPD. These CpGs located on chr3 at positions 8810078 and 8810069 exhibited significant associations with postpartum depression scores from an independent cohort of 240 women with no prior psychiatric history. Hormone analysis suggested a PPD specific negative correlation of DNA methylation in the region with serum estradiol levels. Estradiol levels and OXTR DNA methylation exhibited a significant interaction to associate with the ratio of allopregnanolone to progesterone. Cumulatively, the data corroborate our previous hypotheses of a PPD specific increased sensitivity of epigenetic reprogramming at estrogen target genes and suggests that OXTR epigenetic variation may be an important mediator of mood relevant neuroactive steroid production.

There is considerable public debate over the use of antidepressants in pregnancy. In this article, we offer a commentary on Gail Robinson's important overview of the current controversies. Dr Ronbinson gives a thorough review of the literature, including the risks posed by both antidepressants and depression itself. We summarize her arguments and point out that, in the public conversation, the risks posed to a fetus from antidepressants are consistently overestimated while the risks of untreated depression are consistently underestimated because of the pervasive stigma against mental health. We review recent lay media analyses and urge our fellow physicians to make decisions about prescribing in pregnancy on the basis of evidence and individual patient needs rather than media and stigma.

Background The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression. Methods In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole ( n = 10) or placebo ( n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale. Results All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo ( p = .02). One subject on pramipexole and two on placebo developed hypomanic symptoms. Conclusions The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.

Major depression is twice as common in women as men and depressive episodes appear to be more common in women with bipolar disorder. There is accumulating evidence that, in at least some women, reproductive-related hormonal changes may play a role in increasing the risk of depressive symptoms premenstrually, postpartum and in the perimenopausal period. In this review, the evidence for the role of hormonal fluctuations, specifically estrogen, in triggering depressive symptoms in a subgroup of women is summarized. In addition, the potential role of estrogen in triggering depressive symptoms via its effects on the serotonergic system, brain-derived neurotrophic factor and Protein Kinase C is reviewed.

Background The course of depression in residents of long-term care with dementia is not well studied. Objectives To estimate the incidence, prevalence, and outcomes of depression in long-term care residents with dementia. Method 201 residents of Copper Ridge, a long-term care facility for the memory impaired, were followed every six months during the first year after their admission. Results On admission 19.9% of the residents had depression, the majority (75%) occurring in persons with a prior history of depression. At six months, only 15% of the original 40 depressed patients were still depressed, while at twelve months only 7.5% were depressed. The incidence of depression at six and twelve months was 1.8% and 6.4% respectively. Most persons with new depression at six months were no longer depressed at one year. The annual attack rate (cumulative likelihood of depression over one year) for the total population was 26.4%. The rates for the subgroup of Alzheimer's were similar to the rates of the total population, except for an annual attack rate of 17.5%, reflecting a lower rate of depression on admission. The decline in depression over the year after admission is noteworthy and likely reflects appropriate diagnosis and treatment of depression. Conclusions These results indicate that, over the course of one year, depression afflicts a considerable proportion of long-term care residents with dementia. Admission to a long-term care facility may actually result in a reduction of depression within the year after admission in part due to rapid recognition, appropriate diagnosis and treatment. Copyright © 2002 John Wiley & Sons, Ltd.

The management of psychiatric disorders in women is complicated by reproductive life cycle events. Psychiatric disorders can be initiated or exacerbated during times of hormonal change (such as menarche, the premenstrual period, the postpartum period, and perimenopause), and during the childbearing years, treatment is complicated by pregnancy and breastfeeding. These issues make determining the appropriate psychiatric medications to use in the treatment of mood and anxiety disorders in women complex. This monograph addresses practical approaches in the provision of thorough and individualized care for women with mood or anxiety disorders.