Blood extracellular vesicles carrying brain-specific mRNAs are potential biomarkers for detecting gene expression changes in the female brain.

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.

The immune phenotype of perinatal anxiety in an anxiety-focused behavioral intervention program in Pakistan.

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 (ß = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (ß = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (ß = 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).

Dysregulated placental expression of kynurenine pathway enzymes is associated with inflammation and depression in pregnancy.

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.

Outcomes at the Motherhood Center: A Comparison of Virtual and On-Site Versions of a Specialized Perinatal Partial Hospitalization Program.

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.

Outcomes of the Modified Dunn Procedure Versus Delayed Imhauser Osteotomy for Moderate to Severe Stable Slipped Capital Femoral Epiphysis.

BACKGROUND: Traditional management of moderate to severe stable slipped capital femoral epiphysis (SCFE) has been in situ fixation followed by reconstructive surgery if symptoms arise. This delayed approach may lead to irreversible intra-articular damage of the hip over time. The purpose of this study was to compare radiographic and clinical outcomes of the modified Dunn procedure (MDP) versus in situ fixation followed by delayed Imhauser osteotomy (DIO). METHODS: This was a retrospective study from a single institution between 2001 and 2021. Among 250 patients diagnosed with SCFE, a total of 18 (18 hips) treated with MDP and 16 (18 hips) treated with DIO for moderate to severe stable SCFE were included. Most patients who underwent DIO either had concomitant (11/18 hips) or subsequent (2/18 hips) open osteochondroplasty. Mean follow up was 4.7 years (range: 1 to 12.8 y). Radiographs were reviewed to measure Southwick angle, anteroposterior and lateral alpha (α) angles, and femoral head-neck offset ratio preoperatively and at latest follow up. Charts were reviewed for demographics, subsequent surgeries, complications, and Heyman-Herndon clinical outcomes. RESULTS: The amount of deformity correction was greater in the MDP than DIO group based on anteroposterior α angles (mean: 22.3 vs. 11.9 degrees, P =0.046) and femoral head-neck offset ratios (mean: 0.26 vs. 0.12, P =0.001). There was no significant difference in Heyman-Herndon scores (both 16/18, 88.9% good to excellent outcomes, P >0.999). Less reoperations were performed in the MDP than DIO group (2/18, 11.1% vs. 9/18, 50%; P =0.004). AVN occurred in 2/18 hips (11.1%) in the MDP group with both surgeries performed early in the series and underwent prior in situ screw fixation compared with 0/18 hips (0%) in the DIO group ( P =0.486). One patient in the DIO group was later diagnosed with osteoarthritis. CONCLUSIONS: MDP resulted in more anatomic coronal and sagittal plane deformity correction, less reoperations, and similar Heyman-Herndon clinical outcomes compared with DIO. AVN occurred in the MDP group whereas osteoarthritis occurred in the DIO group. These complications must be weighed against improved long-term clinical results for patients who would otherwise be at risk for premature degenerative joint disease due to residual proximal femoral deformity. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Altered extracellular mRNA communication in postpartum depression is associated with decreased autophagy.

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.

Vitamin D levels and anxiety symptomatology in pregnancy and the postpartum.

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.

Setting Common Standards for Reproductive Psychiatry Education: Effectiveness of the National Curriculum in Reproductive Psychiatry.

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.

A Peer-to-Peer, Longitudinal Reproductive Psychiatry Educational Curriculum for Obstetrics/Gynecology Residents.

OBJECTIVE: Pregnant patients with psychiatric diagnoses are commonly advised to stop their psychiatric medications. Few studies assess the knowledge of, attitude toward, or comfort levels of obstetrics and gynecology (OB/GYN) residents in managing psychiatric conditions, which carry adverse and potentially life-threatening risks to mother and fetus. A gap remains between evidence advocating for active psychopharmacological treatment during pregnancy and implementation of curricula targeting OB/GYN physicians in mental health. The authors' goals are to assess the knowledge, attitude, and comfort that OB/GYN residents have toward assessing and managing active psychiatric conditions in pregnant/postpartum women and to develop an educational, case-based intervention targeting these conditions in the perinatal/postpartum period. METHODS: Eight perinatal/postpartum psychiatric topics were developed into interactive cases designed for OB/GYN residents. Two weeks before the curriculum administration, OB/GYN residents were surveyed on prior knowledge in, attitudes toward, and comfort levels in assessing and discussing psychiatric conditions in pregnant patients. The assessment was administered again after the intervention to assess its effectiveness. RESULTS: Pre- (N = 19) and post-intervention (N = 15) surveys of residents were analyzed. Most residents (94%) felt it was both important and their responsibility to discuss mental health conditions with pregnant patients. Comfort levels with counseling psychiatric patients increased for all eight topics after the educational intervention was implemented, with statistically significant increases (p < 0.05) for five of the topics. CONCLUSIONS: OB/GYN residents feel responsible for caring for pregnant patients with psychiatric illness, and case-based interventions offer an interactive, helpful tool for increasing residents' knowledge and comfort level in treating this patient population.

The immune phenotype of perinatal anxiety.

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:TREG 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.

Perinatal Obsessive-Compulsive Disorder: Epidemiology, Phenomenology, Etiology, and Treatment.

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.

Allopregnanolone and depression and anxiety symptoms across the peripartum: an exploratory study.

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, ß = 3.73 (95% CI:1.16, 6.30), p = 0.0045; for PASS ß = 9.78 (95% CI:3.77, 15.79), p = 0.0014); from T3 to W6, for (EPDS, ß = 2.52 (95% CI:0.08, 4.96), p = 0.043; for PASS ß = 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.

Using the Psychiatry Resident-In-Training Examination (PRITE) to Assess the Psychiatry Medical Knowledge Milestones in Psychiatry.

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.

Polycystic Ovary Syndrome, Affective Symptoms, and Neuroactive Steroids: a Focus on Allopregnanolone.

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.

Lack of psychotropic medication changes among mood disordered women across the peripartum period.

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.

The Crisis of Perinatal Mental Health in the Age of Covid-19.

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.

Indeterminate Prenatal Ultrasounds and Maternal Anxiety: A Prospective Cohort Study.

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.

T-cell defects and postpartum depression.

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 TH1 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.

Maternal behavioral health symptom profiles in early family life: complexity and context.

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.

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders.

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 TH17 cells and dysregulation of the TH17/Treg cell balance in morbidities and autoimmune diseases during pregnancy. Because TH17 responses may play a role in depression and anxiety outside of pregnancy, we hypothesize that TH17 responses and the balance of TH17/Treg 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 TH17 cells and cytokines during pregnancy; 2) to compare changes in the ratio of TH17/Treg 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 TH17 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 TH17 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.