Search

Rationale: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD., Aims: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers., Methods: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1β were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity., Results: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1β, nor TNF-α (p's>0.05)., Conclusion: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD., Competing Interests: Declaration of Competing Interest ALM holds a provisional patent on the anti-inflammatory effects of allopregnanolone and related neurosteroids, and has current and previous funding from Sage Therapeutics related to the anti-inflammatory actions of allopregnanolone. LH has consulted for PureTech Health and Flo Health. JLP has research funding from NIMH and Janssen Pharmaceuticals; served as a consultant to SAGE Therapeutics, Biogen, Merck, Brii Biologics, Pure Tech, Dionysus Health, and Flo Health; speaker for employees of Karuna Therapeutics; founder’s stock in Dionysus Health; two patents: “Epigenetic Biomarkers of Postpartum Depression” and “Epigenetic Biomarkers of PMDD and SSRI Response.” LMO reports no conflicts of interest, but has research funding from NIMH and NICHD and receives royalties and editorial fees from APA Publishing, Elsevier, and UpToDate., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression. Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress., Areas Covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders., Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system. Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines., Expert Opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment. The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders.

Background: Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD), collectively known as Premenstrual Disorders (PMDs), cause significant distress and functional impairment, and premenstrual exacerbation (PME) affects a large proportion of women with psychiatric diagnoses. Childhood trauma is one factor that may contribute to PMD/PME risk. This study examines the relationship between childhood trauma and PMDs, PME, and non-PMD psychiatric illness., Methods: This study is a secondary analysis of data from a prospective cohort. Participants completed self-assessments on childhood trauma using the Childhood Traumatic Event Scale (CTE-S) and on premenstrual symptoms using the Premenstrual Symptoms Screening Tool (PSST). Psychiatric diagnoses were assessed through structured clinical interviews. Participants were divided into four groups based on their PSST scores and psychiatric illness status: (1) Premenstrual Disorders (PMDs; moderate to severe PMS and PMDD), (2) PME, (3) psychiatric controls (PC; individuals with psychiatric illness but no significant premenstrual symptoms), and (4) healthy controls (HC; individuals with no psychiatric illness and no significant premenstrual symptoms). Statistical analyses, including ANOVA, Tukey's HSD test, Fisher's exact test, and logistic regression, were conducted to examine differences among the groups., Results: Data from 391 participants were analyzed. Participants with PME and PC reported a higher quantity and severity of childhood traumatic events compared to HCs (p <.05). There was a weak but significant correlation between childhood trauma and premenstrual symptom burden across all groups (R = .18, p <.001). Within-group analysis revealed moderate correlations between childhood trauma and premenstrual symptoms driven by the PMD group (R = .42, p = .01)., Conclusions: The findings underscore the impact of childhood traumatic events on mental health and premenstrual symptoms and highlight the need for additional research to explore the underlying mechanisms linking childhood trauma to the continuum of premenstrual disorders, to improve the efficacy of trauma-focused interventions for affected individuals., Competing Interests: JP has research funding from NIMH, Janssen Pharmaceuticals and Myriad. She has served as a consultant to SAGE Therapeutics, Biogen, Merck, Brii Biologics, Pure Tech, Dionysus Health, and Flo Health. She has founders stock in Dionysus Health. She has two patents: “Epigenetic Biomarkers of Postpartum Depression” and “Epigenetic Biomarkers of PMDD and SSRI Response.” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Standeven, Bajaj, McEvoy, Shirinian, Voegtline, Osborne, Payne and Hantsoo.)

Competing Interests: Declaration of competing interest The authors do not have any disclosures to make.

Background: Depression and anxiety are common in the perinatal period. While most of those affected respond well to treatment, a subpopulation is more resistant. Understanding more about individuals who do not respond well to available treatments may improve care for this group., Methods: We administered entry and exit self-report measures to 178 women who participated in a specialized partial hospitalization program for perinatal individuals. Baseline measures of anxiety, obsessive symptoms, sleep quality, early life adversity, and adult attachment security were examined as potential predictors of response to treatment., Results: While no individual baseline survey predicted treatment response, clustering patients on the basis of a combination of self-report adult attachment styles and early life adversity yielded four distinct groups. A cluster with high attachment anxiety, high attachment avoidance, and childhood history of verbal and emotional abuse was less responsive to treatment than the other groups., Conclusions: Combining detailed information about self-report adult attachment style and early life adversity may improve prediction of treatment response in individuals with perinatal mood and anxiety disorders., Competing Interests: Declaration of competing interest TKR and LMO receive research funding from the National Institutes of Child Health and Human Development. LMO receives royalties and editorial fees from American Psychiatric Association Publishing, UpToDate, and Elsevier. CB is medical director and CEO of the Motherhood Center of New York (TMC). All other authors except FB and LMO are employees or paid consultants of TMC in some capacity. Besides the above, the authors have no other financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Given that infant development is influenced by caregiver mental health, we tested whether an intervention to reduce antenatal anxiety could affect infant development. A secondary aim was to test depressive symptoms, maternal responsiveness, and maternal infant bonding as mediators of this relationship., Methods: Between 2020 and 2022, pregnant women participated in a randomized controlled trial of the Happy Mother-Healthy Baby (HMHB) program based on cognitive behavioral therapy. We collected data on child development from 202 intervention and 198 control participants in a public hospital in Pakistan. Child development was measured using the Ages and Stages Questionnaires-Version 3 at six weeks postpartum. Using intent-to-treat analyses, we examined whether the intervention was associated with performance on the five ASQ-3 domains. Causal mediation analysis was used to assess depressive symptoms, bonding, and maternal-infant responsiveness as mediators., Results: Socio-demographic characteristics were evenly distributed between study arms. Intervention arm infants showed a 2.1-point increase (95% CI: 0.12, 4.17) in communication scores compared to controls. Though not achieving statistical significance, intervention infants also showed a 2.0-point increase (95% CI:-0.06, 4.09) in gross motor development performance. Bonding, depression, and responsiveness were mediators between the intervention and infant communication (B indirect =1.94 (95%CI: 0.86, 3.25) depression; B indirect =0.57 (95% CI: 0.09, 1.16) bonding; B indirect =0.53 (95% CI: 0.01, 1.21) responsiveness; and B indirect =1.94 (95%CI: 0.86, 3.25). Bonding, responsiveness, and depression mediated 25%, 23%, and 87% of the total association, respectively., Conclusions: HMHB positively affected infant communication at six-week follow-up. Larger studies with longer follow-up are needed to confirm and extend these findings., Trial Registration: ClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms-the Happy Mother - Healthy Baby (HMHB) study in Rawalpindi, Pakistan., Materials and Methods: Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale - HADS -using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded., Results: K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (β = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (β = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (β = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA)., Conclusion: Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Importance: A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking., Objective: To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season., Design, Setting, and Participants: This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024., Exposure: Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records., Main Outcome and Measures: The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed., Results: Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77)., Conclusions and Relevance: In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

Background: Perinatal depression (including antenatal-, postnatal-, and depression that spans both timepoints) is a prevalent disorder with high morbidity that affects both mother and child. Even though the full biological blueprints of perinatal depression remain incomplete, multiple studies indicate that, at least for antenatal depression, the disorder has an inflammatory component likely linked to a dysregulation of the enzymatic kynurenine pathway. The production of neuroactive metabolites in this pathway, including quinolinic acid (QUIN), is upregulated in the placenta due to the multiple immunological roles of the metabolites during pregnancy. Since neuroactive metabolites produced by the pathway also may affect mood by directly affecting glutamate neurotransmission, we sought to investigate whether the placental expression of kynurenine pathway enzymes controlling QUIN production was associated with both peripheral inflammation and depressive symptoms during pregnancy., Methods: 68 placentas obtained at birth were analyzed using qPCR to determine the expression of kynurenine pathway enzymes. Cytokines and metabolites were quantified in plasma using high-sensitivity electroluminescence and ultra-performance liquid chromatography, respectively. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) throughout pregnancy and the post-partum. Associations between these factors were assessed using robust linear regression with ranked enzymes., Results: Low placental quinolinate phosphoribosyl transferase (QPRT), the enzyme responsible for degrading QUIN, was associated with higher IL-6 and higher QUIN/kynurenic acid ratios at the 3rd trimester. Moreover, women with severe depressive symptoms in the 3rd trimester had significantly lower placental expression of both QPRT and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD); impaired activity of these two enzymes leads to QUIN accumulation., Conclusion: Overall, our data support that a compromised placental environment, featuring low expression of critical kynurenine pathway enzymes is associated with increased levels of plasma cytokines and the dysregulated kynurenine metabolite pattern observed in depressed women during pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Remotely administered mental health care is becoming increasingly common for treatment of a range of psychiatric disorders; however, there is a dearth of literature overviewing direct comparisons between remote and in-person interventions for treatment of Perinatal Mood and Anxiety Disorders (PMADs). The sudden advent of the Covid-19 pandemic in New York City forced an abrupt conversion for an intensive day treatment program for new mothers with PMADs, from an on-site to a remote program., Methods: The current report compares outcomes of 81 women who completed the program in-person to those of 60 women who completed the program remotely., Results: Improvement in depression scores was statistically superior in the remote program, and improvement in mother-infant bonding was statistically equivalent between the on-site and remote programs., Discussion: These findings indicate that specialized partial hospitalization treatment for individuals with moderate to severe psychiatric illness can be effectively provided via telehealth, thus offering improved convenience, accessibility, and safety without compromising care. We conclude that remotely administered group psychotherapy is an effective intervention for women with moderate to severe PMADs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The absence of non-invasive tests that can monitor the status of the brain is a major obstacle for psychiatric care. In order to address this need, we assessed the feasibility of using tissue-specific gene expression to determine the origin of extracellular vesicle (EV) mRNAs in peripheral blood. Using the placenta as a model, we discovered that 26 messenger RNAs that are specifically expressed in the placenta are present in EVs circulating in maternal blood. Twenty-three of these transcripts were either exclusively or highly expressed in maternal blood during pregnancy only and not in the postpartum period, verifying the feasibility of using tissue-specific gene expression to infer the tissue of origin for EV mRNAs. Using the same bioinformatic approach, which provides better specificity than isolating L1 cell-adhesion molecule containing EVs, we discovered that 181 mRNAs that are specifically expressed in the female brain are also present in EVs circulating in maternal blood. Gene set enrichment analysis revealed that these transcripts, which are involved in synaptic functions and myelination, are enriched for genes implicated in mood disorders, schizophrenia, and substance use disorders. The EV mRNA levels of 13 of these female brain-specific transcripts are associated with postpartum depression (adjusted p-vals = 3 × 10 -5 to 0.08), raising the possibility that they can be used to infer the state of the brain. In order to determine the extent to which EV mRNAs reflect transcription in the brain, we compared mRNAs isolated from cells and EVs in an iPSC-derived brain microphysiological system differentiated for 3 and 9 weeks. We discovered that, although cellular and extracellular mRNA levels are not identical, they do correlate, and it is possible to extrapolate cellular RNA expression changes in the brain via EV mRNA levels. Our findings bring EV mRNAs to the forefront of peripheral biomarker development efforts in psychiatric diseases by demonstrating the feasibility of inferring transcriptional changes in the brain via blood EV mRNA levels., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Perinatal mood and anxiety disorders (PMADs) are the most common complication of childbirth. When poorly controlled, they are associated with worse obstetric outcomes, such as higher rates of preterm birth and unplanned cesarean delivery. They are also associated with suicide, a leading cause of perinatal maternal death. This article provides an overview of evidence-based recommendations for screening, assessment, and management of PMADs, including suicide risk assessment and management and pharmacological and nonpharmacological treatment options compatible with pregnancy and lactation. Although specialized reproductive psychiatrists can provide expert guidance for the management of PMADs, their scarcity means that most patients will not have access to this expert care and instead will seek guidance from general psychiatrists. This article provides a clinical guide for generalists that is based on the best current evidence, including recently released treatment guidelines., Competing Interests: Dr. Osborne reports receiving royalties from UpToDate and the American Psychiatric Association, editorial fees from Elsevier, and research support from NIH. Dr. Weingarten reports no financial relationships with commercial interests., (Copyright © 2024 by the American Psychiatric Association.)

Anxiety and vitamin D deficiency are both common in pregnancy, but research into the relationship between vitamin D levels and perinatal anxiety is sparse. We sought to examine whether an association exists and compare the distribution of vitamin D levels in women with and without anxiety symptoms. We analyzed 25-hydroxyvitamin D using ab213966 25(OH) vitamin D enzyme-linked immunosorbent assay in 54 women with and 47 women without anxiety symptoms at the first, second, and third trimesters and at 6 weeks postpartum. We conducted univariate and chi-square analyses to compare the frequencies of non-optimal and optimal vitamin D levels between the anxiety and non-anxiety groups at each timepoint. Overall, vitamin D levels were lower in the first and second trimesters than in the third trimester. In the first trimester only, the non-anxiety group had a marginally higher proportion of women with optimal vitamin D levels when compared to the anxiety group. Many pregnant women have insufficient or deficient levels of vitamin D, and our exploratory findings point to the need for further research into whether this differs between women with anxiety compared to healthy women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Postpartum depression has deleterious effects on childbearing persons globally. Existing treatments have been largely extrapolated from those for other forms of depression and have included pharmacotherapy, psychotherapy, and neuromodulation. Hormonal treatments with oestrogen and progestogens, thought to be a rational approach to treatment in response to an emerging literature on the pathophysiology of postpartum depression, have only limited evidence for efficacy to date. Novel antidepressant development with allopregnanolone analogues, in contrast, has proven a promising avenue for the development of rationally designed and efficacious treatments. This state-of-the-art review presents the evidence for the current standard-of-care pharmacotherapy, hormonal treatment, and emerging allopregnanolone analogues for the treatment of postpartum depression along with a discussion of the current understanding of its neuroactive steroid-driven pathophysiology.

Background: Anxiety disorders are the most common psychiatric disorder during the perinatal period and one of the major risk factors for postpartum depression, yet we know little about biological factors in the etiology of perinatal anxiety. A growing literature points to neuroactive steroid (NAS) dysregulation in perinatal mental illness, but directionality has not been clearly demonstrated, results are not consistent, and no studies have investigated NAS in a population with pure anxiety without comorbid depression. We aimed to add to the limited literature by examining the association between anxiety without comorbid depression and metabolic pathways of NAS longitudinally across the peripartum., Methods: We measured anxiety symptoms by psychological scales and NAS levels using Gas Chromatography-Mass Spectrometry (GC-MS) at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in n = 36 women with anxiety and n = 38 healthy controls. The anxiety group was determined by a data-driven approach, and cross-sectional and longitudinal statistical methods were used to examine the relationship between the study population and NAS., Results: We found that anxiety had a significant moderating effect on the relationship between progesterone and allopregnanolone, with no such effect for the relationships between progesterone and the intermediate (5α-DHP) or isomeric (isoallopregnanolone) compounds in this pathway, and no effects on the corresponding pathway converting progesterone to pregnanolone and epipregnanolone. We also found a less precipitous decline in the ratio of allopregnanolone to progesterone between T3 and W6 in the anxiety group compared to the non-anxiety group. A genotype analysis of a single-nucleotide polymorphism in the AKR1C2 gene demonstrated that the relationship of allopregnanolone to the intermediate metabolite, 5α-DHP, differed by genotype., Conclusion: Our exploratory findings indicate that, for pregnant people with anxiety, metabolism is shunted more aggressively toward the endpoint of the progesterone to allopregnanolone metabolic pathway than it is for those without anxiety., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Payne has served as a consultant for SAGE Therapeutics, Biogen, Brii Biologics, and Pure Tech. Dr. Payne also holds a patent entitled “Epigenetic Biomarkers of Postpartum Depression.” Dr. Pinna is a paid consultant to PureTech Health (Boston, MA, USA), GABA Therapeutics, and NeuroTrauma Sciences (Alpharetta, GA, USA). He has two patent applications, one on N-palmitoylethanolamine (PEA) and peroxisome proliferator-activated receptor alpha (PPAR-α) agonists US20180369171A1, pending, and one on allopregnanolone analogs US11266663B2 granted on March 8, 2022, in the treatment of neuropsychiatric disorders. The other authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The present study aimed to explore the association between anxiety symptoms, including sleep, and physiological stress responsiveness in pregnant women with and without anxiety, as identified by psychiatric diagnosis. Fifty-four pregnant women with (n = 25) and without (n = 29) anxiety completed a laboratory cognitive stressor (the Stroop Color-Word Task) during the third trimester. Heart rate variability (HRV) (as the root mean square of successive differences, RMSSD) was recorded during baseline, stressor, and recovery periods. Salivary cortisol (sCORT) and alpha amylase (sAA) were measured at four timepoints surrounding the stressor task. Psychometric scales (Penn State Worry Questionnaire [PSWQ], Perceived Stress Scale [PSS], Spielberg Trait Anxiety Inventory Scale [STAI], and Pittsburgh Sleep Quality Index [PSQI]) were collected. Women in the anxiety group exhibited significantly less rebound in HRV (RMSSD, change of 4-ms difference, p = .025) from baseline to recovery following the Stroop than did those in the non-anxiety group. Neither neuroendocrine measure (sCORT, sAA) differed between groups at any measurement period. Across the recording period, lower reported sleep quality (PSQI, p = .0092) and higher subjective stress (PSS, p = .039) were associated with lower RMSSD. The findings suggest that women with and without anxiety in late pregnancy display differences in the degree of autonomic rebound as indicated by HRV following a stressor. In addition, levels of HRV over time were associated with subjective perceptions of increased stress and poor sleep. PREGNANCY AND ANXIOUS: The Role of the Immune and Endocrine Systems (NCT03664128)., (© 2023 British Society for Neuroendocrinology.)

Background: Anxiety and depression are common in the perinatal period and negatively affect the health of the mother and baby. Our group has developed "Happy Mother-Healthy Baby" (HMHB), a cognitive behavioral therapy-based psychosocial intervention to address risk factors specific to anxiety during pregnancy in low- and middle-income countries (LMICs)., Objective: The purpose of this study is to examine biological mechanisms that may be linked to perinatal anxiety in conjunction with a randomized controlled trial of HMHB in Pakistan., Methods: We are recruiting 120 pregnant women from the Holy Family Hospital, a public facility in Rawalpindi, Pakistan. Participants are assessed for at least mild anxiety symptoms using the Hospital Anxiety and Depression Scale (ie, a score ≥8 on the anxiety scale is necessary for inclusion in the anxiety groups and <8 for inclusion in the healthy control group). Women who meet the criteria for an anxiety group are randomized into either the HMHB intervention group or an enhanced usual care (EUC) control group. Participants receive HMHB or EUC throughout pregnancy and undergo blood draws at 4 time points (baseline, second trimester, third trimester, and 6 weeks post partum). We will assess peripheral cytokine concentrations using a multiplex assay and hormone concentrations using gas chromatography and mass spectrometry. The statistical analysis will use generalized linear models and mixed effects models to assess the relationships across time among anxiety, immune dysregulation, and hormone levels, and to assess whether these biological factors mediate the relationship between anxiety and birth and child development outcomes., Results: Recruitment started on October 20, 2020, and data collection was completed on August 31, 2022. The start date for recruitment for this biological supplement study was delayed by approximately half a year due to the COVID-19 pandemic. The trial was registered at ClinicalTrials.gov (NCT03880032) on September 22, 2020. The last blood samples were shipped to the United States on September 24, 2022, where they will be processed for analysis., Conclusions: This study is an important addition to the HMHB randomized controlled trial of an intervention for antenatal anxiety. The intervention itself makes use of nonspecialist providers and, if effective, will represent an important new tool for the treatment of antenatal anxiety in LMICs. Our biological substudy is one of the first attempts to link biological mechanisms to antenatal anxiety in an LMIC in the context of a psychosocial intervention, and our findings have the potential to significantly advance our knowledge of the biological pathways of perinatal mental illness and treatment efficacy., Trial Registration: ClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032., International Registered Report Identifier (irrid): DERR1-10.2196/43193., (©Morgan L Sherer, Abid Malik, Lauren M Osborne, Armaan A Rowther, Ahmed Zaidi, Najia Atif, Atif Rahman, Lubna E Kahloon, Muhammad Salman, Gayane Yenokyan, Pamela J Surkan. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.04.2023.)

Objective: The National Curriculum in Reproductive Psychiatry (NCRP) provides standardized education for psychiatry residency training programs. The authors hypothesized that residents' preparedness to treat reproductive psychiatric concerns and their medical knowledge would improve following teaching with the NCRP., Methods: Pre- and post-assessments were administered to residents enrolled in two waves of pilot NCRP training (Early-Modules and All-Modules). Data were collected by individual survey, and pre- and post-responses matched via anonymous ID. Statistical analyses were conducted using R version 3.5.3 and included paired Student's t-tests and a chi-square test., Results: Thirty-eight residents completed the Early-Modules survey and 16 the All-Modules survey. In both groups, there was significant improvement in preparedness to treat pregnant and postpartum women with mental illness (p<0.05). Scores on the 29-point knowledge test rose by 2.5 points in the Early-Modules group and 4.3 points in the All-Modules group (p<0.001 for both). In both cohorts, a majority of residents felt reproductive psychiatry was among the top three specialties needed to become competent independent adult psychiatrists., Conclusions: Classroom training with local faculty using a standardized curriculum is feasible and results in substantial and significant improvements in both feelings of preparedness and medical knowledge. Psychiatry trainees view training in reproductive psychiatry as an important and missing aspect of their education. Dissemination of a standardized curriculum may help to forge a path toward subspecialty certification for reproductive psychiatry, and can be used as a model for other specialties., (© 2022. The Author(s), under exclusive licence to American Association of Chairs of Departments of Psychiatry, American Association of Directors of Psychiatric Residency Training, Association for Academic Psychiatry and Association of Directors of Medical Student Education in Psychiatry.)

We investigated whether extracellular RNA communication, which is a recently discovered mode of intercellular communication that is involved in a variety of important biological processes including pregnancy, is associated with postpartum depression (PPD). Extracellular RNA communication is increased during pregnancy and is involved in embryo implantation, uterine spiral artery remodeling, parturition, preterm birth, immunity, and the inflammatory response. Since immune anomalies are associated with PPD, we characterized the mRNA content of extracellular vesicles (EV) in a cohort of prospectively collected blood plasma samples at six time-points throughout pregnancy and the postpartum (2nd trimester, 3rd trimester, 2 weeks postpartum, 6 weeks postpartum, 3 months postpartum, and 6 months postpartum) in an academic medical setting from women who went on to develop PPD (N = 7, defined as euthymic in pregnancy with postpartum-onset depressive symptoms assessed by Edinburgh Postnatal Depression Scale ≥13 at any postpartum time point) and matched unaffected controls (N = 7, defined as euthymic throughout pregnancy and postpartum). Blood samples were available for all participants at the T2 and W6 timepoints, with fewer samples available at other time points. This analysis revealed that EV mRNA levels during pregnancy and the postpartum period were extensively altered in women who went on to develop PPD. Gene set enrichment analysis revealed that mRNAs associated with autophagy were decreased in PPD cases. In contrast, EV mRNAs from ribosomes and mitochondria, two organelles that are selectively targeted by autophagy, were elevated in PPD cases. Cellular deconvolution analysis discovered that EV mRNAs associated with PPD originated from monocytes and macrophages. Quantitative PCR analysis for four relevant genes in another cohort replicated these findings and confirmed that extracellular RNA levels are altered in PPD. We demonstrate that EV mRNA communication is robustly altered during pregnancy and the postpartum period in women who go on to develop PPD. Our work also establishes a direct link between reduced autophagy and PPD in patient samples. These data warrant investigating the feasibility of developing EV mRNA based biomarkers and therapeutic agents for PPD., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety., Materials and Methods: Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6). Each visit included a blood draw and psychological evaluation, with clinical anxiety assessed using the Spielberg State-Trait Anxiety Scale. We enrolled both healthy controls and participants with anxiety alone; those with comorbid depression were excluded. Multiplex cytokine assays and flow cytometry were used to examine the association of anxiety symptoms with secreted immune markers and PBMC-derived immune cells., Results: K cluster means revealed three clusters of anxiety symptomatology; due to low numbers in the highest severity anxiety group, these were collapsed into two groups: Non-Anxiety and Anxiety. Principal components analysis revealed two distinct clusters of cytokine secretion including one cluster that consisted of many innate immune cytokines and differed between groups. Compared to women in the Non-Anxiety group, women in the Anxiety group had lower levels of cytokine expression during pregnancy and an increase in levels into the postpartum, whereas Non-Anxiety women experienced a time-dependent decline. Immune cell populations also differed between our two groups, with the Anxiety group showing a decrease in the ratio of B cells to T cells from pregnancy to postpartum, whereas the Non-Anxiety women showed an increase in this ratio over time. Women in the Anxiety group also demonstrated an increased ratio of cytotoxic to helper T cells throughout pregnancy, a modest increase in the Th1:Th2 ratio across pregnancy, and a lower ratio of Th17:T REG cells in the postpartum as compared with Non-Anxiety women., Conclusion: These data suggest that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The introduction of the Milestone Project underscored the need for objective assessments of resident progress across the competencies. Therefore, the authors examined the Psychiatry Resident-In-Training Examination (PRITE) utility for measuring improvements in medical knowledge (MK)., Methods: The authors compared the mean performance for each MK subcompetency by resident year for all residents taking the PRITE from 2015 to 2017 (18,175 examination administrations). In addition, they surveyed psychiatry residency program directors regarding how well they thought they teach these subcompetencies., Results: Increases in MK subcompetencies by resident year were significant for Psychopathology (p < 0.003), Psychotherapy (p < 0.002), and Somatic Therapies (p < 0.000). Development, Clinical Neuroscience, and Practice of Psychiatry did not show statistically significant differences between postgraduate years. Eighty psychiatry program directors responded to the survey and felt optimistic about their ability to teach the Psychopathology, Psychotherapy, Somatic Therapies, and Practice of Psychiatry subcompetencies., Conclusions: The PRITE measured significant improvements in medical knowledge for several of the core subcompetencies. The program director's responses would suggest that the lack of statistically significant differences found for Development and Clinical Neuroscience reflects areas in need of curricular development. The disparity between PRITE performance and program director perception of the Practice of Psychiatry subcompetency may reflect difficulties in defining the scope of this subcompetency. Overall, this suggests that structured examinations help measure improvements in certain subcompetencies and may also help identify curricular needs. However, there may be potential problems with the definition of some subcompetencies., (© 2021. Academic Psychiatry.)

Purpose of Review: We review recent evidence concerning the epidemiology, etiology, and treatment of obsessive-compulsive disorder (OCD) in the perinatal period. We examine studies reporting on rates of both new-onset OCD and exacerbation in both pregnancy and postpartum; explore both biological and psychosocial risk factors for the disorder; and review the latest evidence concerning treatment., Recent Findings: Evidence is limited in all areas, with rates of both OCD and subthreshold obsessive-compulsive symptoms varying widely across studies. Prevalence is likely higher in the perinatal period than in the general population. Clinical features in the perinatal period are more likely than at other times to concern harm to the child, with contamination and aggressive obsessions and cleaning and checking compulsions especially common. Research into the biological etiology is too limited at this time to be definitive. Both observational and randomized controlled trials support cognitive behavioral therapy with exposure and response prevention (CBT with ERP) as a first-line treatment, with limited evidence also supporting the use of selective serotonin reuptake inhibitors (SSRIs). Treatment considerations in the perinatal period must weigh the risks of treatment vs. the risks of untreated illness. Perinatal OCD is common and can be impairing. Clinical features differ somewhat compared to non-perinatal periods. Treatment does not differ from that used in the general population, though evidence pertaining specifically to the perinatal period is sparse., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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  < 0.001), and were most closely aligned with the TRAIT scale of Spielberg State-Trait Anxiety Scale. Participants with a history of any mood or anxiety disorder had significantly higher worry scores ( t s range = 3.70-6.69, p s < 0.01). Individuals with a current diagnosis were more likely to be high worriers (χ 2  = 8.26, p  = 0.004 and χ 2  = 34.99, p  < 0.001 for major depressive disorder and generalized anxiety disorder, respectively). Conclusions: The PSWQ correlated well with all psychological scales, especially TRAIT anxiety. Worry appears to be a major component of perinatal anxiety, and the PSWQ may be a valuable tool for more precise specification of the clinical phenotypes of perinatal anxiety. Limitations include a study population that was largely Caucasian and well educated, so study results require replication in a more diverse population.

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 < .004 for MDD and <0.001 for all others. High antenatal worry was the only significant predictor of PPDS, with an OR of 3.91 (95% CI 1.44-10.65); neither psychiatric diagnosis nor elevated antenatal depressive symptoms was significantly associated with PPDS in a multivariate model., Limitations: Our study used self-report measures in a largely homogeneous population, which may limit the generalizability of our results., Conclusions: The PSWQ may be a useful clinical tool in pregnancy. High worry is a strong predictor of PPDS, and is a better predictor of PPDS than psychiatric diagnosis or elevated antenatal depressive symptoms in this population., (Copyright © 2021. Published by Elsevier B.V.)

Mental health disorders are common and have a significantly negative impact on the health and well-being of women. For example, perinatal mental health disorders such as anxiety and depression are widely understood to be the most common complications of pregnancy and childbirth. Untreated mental health disorders are associated with significant obstetrical and psychiatric sequelae and have a long-lasting impact on neonatal and childhood outcomes. As front-line providers for women during times of elevated risk of psychiatric morbidity, such as pregnancy and postpartum, obstetricians and gynecologists are compelled to have familiarity with such disorders. Yet, a wide gap exists between the level of education in mental health disorders that obstetrician and gynecologist providers receive and the clinical need thereof. The objectives of this commentary are to describe the urgent need for mental health education for obstetricians and gynecologists providers and to introduce our vision for a concise, evidence-based and accessible set of digital educational materials designed to convey core concepts in women's reproductive mental health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© 2021 John Wiley & Sons Ltd.)

Introduction: Prenatal ultrasounds often yield indeterminate (incomplete or minor abnormality) findings with limited clinical utility. We evaluate impact of indeterminate findings on maternal anxiety., Methods: A single-U.S.-center prospective cohort study administered the Perinatal Anxiety Screening Scale (PASS; control mean = 13.4; > 20 denotes clinically significant anxiety) before and after prenatal ultrasounds in February-May 2017. Ultrasound reports were coded as: normal; indeterminate; or major abnormality. Primary outcome was anxiety after indeterminate vs. normal ultrasounds. Secondary outcomes included anxiety change from pre-to-post-ultrasound and relative to women's characteristics. Linear regression adjusted for confounders., Results: Of 286 ultrasounds, 51.0% were normal, 40.5% indeterminate (22.0% incomplete; 18.5% minor abnormality), and 8.0% major abnormalities. Indeterminate findings were unrelated to age, race, parity, infertility, or psychiatric history, but associated with gestational age (26.6%/45.0%/52.5% for first/second/third trimesters; p < 0.001), and obesity (48.8 vs. 37.0%; p = 0.031). Pretest anxiety was highest in second/third trimesters (p = 0.029), and in subjects aged age ≤ 24 or younger(p < 0.001), with a history of anxiety (p < 0.001),) or with prior pregnancy loss (p = 0.011). Mean anxiety score decreased pre-to-posttest across all groups. Indeterminate findings were associated with higher PASS scores than normal findings: pretest 20.1 vs. 16.4 (p = 0.026) and posttest 16.9 vs. 12.2 (p = 0.009; adjusted-p = 0.01). Versus normal ultrasounds, incomplete findings were associated with higher post-ultrasound anxiety (p = 0.007; adjusted-p = 0.01) and smaller decreases from pre-to-posttest (adjusted-p = 0.03), whereas minor abnormalities had higher pretest anxiety (p = 0.029) with larger pre-to-posttest decreases (adjusted-p =0.010)., Discussion: Indeterminate ultrasounds, especially incomplete findings, are associated with significantly higher anxiety than normal findings, suggesting need for evidence-based counseling, management and strategies for decreasing number of indeterminate results.

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. 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.

In the US, the COVID-19 pandemic adds a new source of stress for women in the perinatal period, a time when stress and anxiety are already heightened. The closures of physical mental health care spaces and lack of support could have devastating impacts on the health of postpartum women and their newborns. Yet, the pandemic creates an opportunity to innovate in the ways mental health care is delivered to pregnant and postpartum women. With the expanded capacity for video and telephone visits, researchers should continue to explore solutions for providing support networks to this vulnerable population.

Mood and anxiety disorders are vastly overrepresented in women, and one important contributor to these differences is the fluctuation in sex steroids in women during the reproductive years. Considerable evidence supports a role for abnormal sensitivity to these hormonal fluctuations for some women, who develop mood symptoms associated with reproductive transitions. This chapter presents evidence of the role of endogenous progesterone and its metabolites in such mood symptoms, and then goes on to cover the evidence concerning exogenous progesterone's effects on mood. Overall, the literature does not support an association between exogenous progesterone and negative mood in the general population, but does indicate that subset of women may be vulnerable to such effects. Research is lacking on women with psychiatric illness., Competing Interests: Declaration of Competing Interest All authors report no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Aim: Our objective was to integrate lessons learned from perinatal collaborative care programs across the United States, recognizing the diversity of practice settings and patient populations, to provide guidance on successful implementation., Background: Collaborative care is a health services delivery system that integrates behavioral health care into primary care. While efficacious, effectiveness requires rigorous attention to implementation to ensure adherence to the core evidence base., Methods: Implementation strategies are divided into three pragmatic stages: preparation, program launch, and program growth and sustainment; however, these steps are non-linear and dynamic., Findings: The discussion that follows is not meant to be prescriptive; rather, all implementation tasks should be thoughtfully tailored to the unique needs and setting of the obstetric community and patient population. In particular, we are aware that implementation on the level described here assumes commitment of both effort and money on the part of clinicians, administrators, and the health system, and that such financial resources are not always available. We conclude with synthesis of a survey of existing collaborative care programs to identify implementation practices of existing programs.

Background: Most studies of immune dysregulation in perinatal mood and anxiety disorders have focused on peripheral cytokines, but literature from non-perinatal mood disorders also implicates T-cell defects. We sought to characterize proportions of T-cell subtypes in women with postpartum depression., Materials and Methods: We enrolled 21 women with postpartum depression (PPD), 39 healthy postpartum controls, and 114 healthy non-postpartum women. Blood was collected in sodium-heparin EDTA tubes and was analyzed using flow cytometry. We conducted statistical tests including linear regression analysis that were aimed at determining differences in proportions of T cell populations among groups., Results: Mean counts of T-cells (all CD3+ T cells), T-helper cells, (CD3+CD4+ T cells), and T-cytotoxic cells (CD3+CD8+ T cells) were significantly increased in healthy postpartum women compared to healthy non-postpartum controls (p < 0.001, p = 0.007, and p = 0.002, respectively), but not in women with PPD. The increases in healthy postpartum women were driven by increases in T H 1 cells and T regulatory cells, increases that were nonexistent or attenuated in women with postpartum depression. Mean counts of CD4+ T-helper memory cells were also increased in healthy postpartum women (p = 0.009), but slightly decreased in women with PPD (p = 0.066), when compared to healthy non-postpartum controls., Conclusions: Our study confirms that the postpartum period in healthy women is a time of enhanced T cell activity. Women with postpartum depression failed to show physiological enhanced T-cell activity postpartum, and future research is needed to elucidate etiological mechanisms and consequences., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Behavioral health problems affect at least 15% of mothers, but few studies have examined how different problems cluster together. Characterizing symptom profiles and their correlates early in the family life cycle can extend existing understanding beyond that provided by studies based on single problems. Mothers in the Fragile Families and Child Wellbeing study, a national birth cohort of racially diverse and mostly unmarried mothers (N = 4205), reported depression, anxiety, and substance dependence symptoms. Latent class analysis (LCA) identified mothers' symptom profiles in their children's third year. We explored associations between symptom profiles and demographics, reproductive health outcomes, functional limitations, and postpartum behavioral health. LCA identified five profiles: (1) Depression only (14.5% of sample), (2) Severe depression and anxiety (5.3%), (3) Anxiety only (2.2%), (4) Depression and substance use (1.4%), and (5) Currently symptom free (76.6%). Depressive symptoms were more moderate when co-occurring with substance dependence and more severe when co-occurring with anxiety. Postpartum depression, postpartum anxiety, and smoking during pregnancy were the most robust correlates of being symptomatic in year 3. Mothers in the "Severe depression and anxiety" group were more likely to be in that profile if they reported functional impairment and/or relationship dissolution. Mothers in the "Depression only" profile were more likely to have higher parity and/or functional impairment. A quarter of mothers of young children had significant behavioral health symptoms, with most reporting depression symptoms. Psychosocial and physical health factors in the pregnancy and postpartum periods were associated with future symptoms, warranting obstetrician and pediatrician attention.

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., Competing Interests: Conflict of Interest Z.K. and J.P. are listed as investors on a patent to use the above biomarkers to predict postpartum depression. Z.K. is the founder of and holds equity in METHYX LLC. He also serves as the company's Managing Member. METHYX LLC intends to license technology used in the study that is described in this publication. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. J.P. received legal consulting fees from Astra Zeneca, Eli Lilly, Johnson & Johnson, and Abbott Pharmaceuticals and received research support from the NIMH, the Stanley Medical Research Foundation, and SAGE Therapeutics. No additional conflicts of interest are noted., (Copyright © 2019. Published by Elsevier B.V.)

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., (© 2019 American Academy of Sleep Medicine.)

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.

Psychiatric symptoms that coincide with reproductive transitions are related to changes in sex steroids, but studies show that this relationship is governed by individual women's vulnerability to change rather than by differences in level. There is growing interest in the role of allopregnanolone (ALLO), a 3- α reduced metabolite of progesterone and a strong allosteric modulator of the GABA A receptor, in such symptoms, with enough evidence now across various times of reproductive transition to offer an overview of the role of this hormone in reproductive psychiatry. This review offers a brief overview, focusing on literature of the last 3 years, of the relationship between allopregnanolone and mood at menarche; in the menstrual cycle; in the peripartum; and in the menopausal transition. ALLO dysregulation is identified in all of these transitions and found to be associated with mood symptoms, although evidence of its exact role; its relationship to other systems; and directionality is not consistent.

T cells play a key role in adaptive immune responses, and shifts among T cell classes occur in normal pregnancy. There is evidence for the role of T H 17 cells and dysregulation of the T H 17/T reg cell balance in morbidities and autoimmune diseases during pregnancy. Because T H 17 responses may play a role in depression and anxiety outside of pregnancy, we hypothesize that T H 17 responses and the balance of T H 17/T reg activity may also contribute to the development of depression and anxiety during pregnancy. To explore this hypothesis, this review has three main aims: 1) to evaluate systematically the role of T H 17 cells and cytokines during pregnancy; 2) to compare changes in the ratio of T H 17/T reg cells during pregnancy morbidities with the changes that occur in depression and anxiety outside of pregnancy; and 3) to provide a basis for further research on T H 17 cells in perinatal mood and anxiety disorders, with an eye toward the development of novel therapeutics. We also review the limited literature concerning perinatal mood and anxiety disorders, and hypothesize about the potential role of T H 17 cells in these illnesses. Understanding the pathophysiology of perinatal mood and anxiety disorders will aid development of novel therapeutics that address immunological mechanisms, in addition to the serotonin system, which are targetable molecules in treating depression and anxiety during pregnancy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This study sought to assess the prevalence of moonlighting among psychiatry residents; the perceived effects of moonlighting on resident recruitment, education, and liability; and policies and practices governing oversight., Methods: In 2013, surveys were emailed to all general psychiatry residency programs that were accredited by the Accreditation Council for Graduate Medical Education and had available contact information (n = 183). Resident surveys were emailed to program coordinators with a request to forward the survey link to their residents., Results: Responses were received from 63 program directors (34% response rate) and 238 residents (about 5% of total general psychiatry residents). Most psychiatry program directors (95%) indicated that their programs permit moonlighting. Moonlighting participation increased with each year of training, culminating with 67% of fourth year residents. Most residents and faculty (87%) agreed that moonlighting enhanced resident education. Thirty-seven percent of program directors reported having no oversight procedures in place to monitor moonlighting activities. Thirty-nine percent of resident survey responders reported having no supervision for at least one of their moonlighting activities and only 9% reported always having access to on-site supervision., Conclusion: Though limited by a low response rate, this study found that moonlighting seems to remain prevalent among psychiatry residents and widely accepted by psychiatry residency training programs. There appears to be relatively limited program oversight for moonlighting activities, many of which seem to lack close supervision.

Background: There are complex associations between immune function and mental illness, yet studies in the perinatal period focus primarily on individual inflammatory markers and depressive symptoms only, cross-sectionally. We sought to examine associations between both depressive and anxious symptoms and immune activation longitudinally across the peripartum., Methods: We measured mood (Beck Depression Inventory, BDI-1 A) and anxiety (State-Trait Anxiety Inventory, STATE) and levels of 23 cytokines at 5 points in pregnancy and postpartum in 51 women. Within subject cytokine trajectories over time by depressive and anxious symptom grouping were assessed using linear mixed effects models with random intercept and slope. We also undertook an exploratory cluster analysis based on third trimester cytokine values., Results: Based on categorical BDI scores, IL-6 (p <  0.001), IL-15 (p =  0.047), GCSF (p = 0.003), and CCL3 (p < .001) were significantly different across time, with IL-6 (p <  0.001), IL-15 (p =  0.003), and CCL3 (p <  0.001) higher at the third trimester visit in more depressed subjects. Based on categorical STATE scores, GM-CSF significantly decreased across pregnancy for the less anxious group (p = 0.016), but not for the more anxious, and CCL3 (p = 0.017), CXCL8 (p = 0.011), and IL-6 (p < 0.001) were higher at the third trimester visit for more anxious subjects. In exploratory cluster analysis based on cytokine level, there were no differences in mood or anxiety scores, but significant differences by race/ethnicity and overweight/obesity status. Women with higher pro-inflammatory cytokine values are more likely to be Hispanics (69.2% vs. 21.4%, p =  0.015), but less likely to be African American (23.1% vs. 60.7%, p = 0.015) or overweight/obese (25% vs. 69.2%, p =  0.016) compared to women with lower pro-inflammatory cytokine values., Conclusion: We identified a pro-inflammatory burst at the third trimester, indicative of innate immune activation, in women with higher levels of both depressive and anxious symptoms, as well as differences in pro-inflammatory changes across time. We also found significant differences in cytokine levels by race, ethnicity, and overweight/obesity status. These results point the way toward future longitudinal work that considers race/ethnicity, timing, and weight status, and evaluates perinatal mood and anxiety disorders in the context of changing immune functioning across the peripartum., (Copyright © 2018 Elsevier Ltd. All rights reserved.)