Adverse life events, psychiatric history, and biological predictors of postpartum depression in an ethnically diverse sample of postpartum women.

BACKGROUND: Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case-control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry. METHODS: We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD. RESULTS: This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids. CONCLUSIONS: Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study.

BACKGROUND: Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. METHODS: Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. RESULTS: Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). CONCLUSIONS: ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience.

Obstetrical, pregnancy and socio-economic predictors for new-onset severe postpartum psychiatric disorders in primiparous women.

BACKGROUND: Childbirth is a potent trigger for the onset of psychiatric illness in women including postpartum depression (PPD) and postpartum psychosis (PP). Medical complications occurring during pregnancy and/or childbirth have been linked to postpartum psychiatric illness and sociodemographic factors. We evaluated if pregnancy and obstetrical predictors have similar effects on different types of postpartum psychiatric disorders. METHOD: A population-based cohort study using Danish registers was conducted in 392 458 primiparous women with a singleton delivery between 1995 and 2012 and no previous psychiatric history. The main outcome was first-onset postpartum psychiatric episodes. Incidence rate ratios (IRRs) were calculated for any psychiatric contact in four quarters for the first year postpartum. RESULTS: PPD and postpartum acute stress reactions were associated with pregnancy and obstetrical complications. For PPD, hyperemesis gravidarum [IRR 2.69, 95% confidence interval (CI) 1.93-3.73], gestational hypertension (IRR 1.84, 95% CI 1.33-2.55), pre-eclampsia (IRR 1.45, 95% CI 1.14-1.84) and Cesarean section (C-section) (IRR 1.32, 95% CI 1.13-1.53) were associated with increased risk. For postpartum acute stress, hyperemesis gravidarum (IRR 1.93, 95% CI 1.38-2.71), preterm birth (IRR 1.51, 95% CI 1.30-1.75), gestational diabetes (IRR 1.42, 95% CI 1.03-1.97) and C-section (IRR 1.36, 95% CI 1.20-1.55) were associated with increased risk. In contrast, risk of PP was not associated with pregnancy or obstetrical complications. CONCLUSIONS: Pregnancy and obstetrical complications can increase the risk for PPD and acute stress reactions but not PP. Identification of postpartum women requiring secondary care is needed to develop targeted approaches for screening and treatment. Future work should focus on understanding the contributions of psychological stressors and underlying biology on the development of postpartum psychiatric illness.

The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

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

Maternal Childhood Sexual Trauma and Early Parenting: Prenatal and Postnatal Associations.

Existing research suggests that approximately 19% of females experience childhood sexual trauma (CST). Little is known, however, about the parenting behaviour of mothers who have experienced CST. Using propensity-matched controls, the present study examines prenatal psychosocial distress, postnatal depressive symptomatology, and caregiving behaviours of women reporting CST at or before the age of 14. Data for these analyses were obtained from mother reports and from observational protocols from a longitudinal study of low-income, rural families. Propensity score methodology was used to create a contrast group matched on family of origin variables in an effort to isolate and examine the long-term associations of CST beyond the effects of other childhood adversities such as poverty. Study findings provide evidence that women with CST histories report greater prenatal psychosocial distress compared to women without trauma histories. Findings further provide evidence for a spillover process from prenatal distress to the broader caregiving system including less sensitive parenting through postnatal depressive symptoms for women with CST histories. These results highlight the importance of screening for CST and psychosocial distress and depression prenatally. Interventions for women with CST histories and directions for future study are proposed.

Noninvasive Imaging of CCR2+ Cells in Ischemia-Reperfusion Injury After Lung Transplantation.

Ischemia-reperfusion injury-mediated primary graft dysfunction substantially hampers short- and long-term outcomes after lung transplantation. This condition continues to be diagnosed based on oxygen exchange parameters as well as radiological appearance, and therapeutic strategies are mostly supportive in nature. Identifying patients who may benefit from targeted therapy would therefore be highly desirable. Here, we show that C-C chemokine receptor type 2 (CCR2) expression in murine lung transplant recipients promotes monocyte infiltration into pulmonary grafts and mediates graft dysfunction. We have developed new positron emission tomography imaging agents using a CCR2 binding peptide, ECLi1, that can be used to monitor inflammatory responses after organ transplantation. Both 64 Cu-radiolabeled ECL1i peptide radiotracer (64 Cu-DOTA-ECL1i) and ECL1i-conjugated gold nanoclusters doped with 64 Cu (64 CuAuNCs-ECL1i) showed specific detection of CCR2, which is upregulated during ischemia-reperfusion injury after lung transplantation. Due to its fast pharmacokinetics, 64 Cu-DOTA-ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent 64 CuAuNCs-ECL1i with extended pharmacokinetics is favored for long-term CCR2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune-mediated diseases.

Obstetric and gynecologic problems associated with eating disorders.

OBJECTIVE: This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders. METHOD: We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized-controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers. RESULTS: Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder. DISCUSSION: We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.

Treatment of severe perinatal mood disorders on a specialized perinatal psychiatry inpatient unit.

Perinatal patients with bipolar and psychotic mood disorder exacerbations are challenging to treat and often receive suboptimal care. We sought to examine the treatment patterns and outcomes on one of the only US-based Perinatal Psychiatry Inpatient Units (PPIU). Perinatal patients admitted to the PPIU completed self-report measures at admission and before discharge. Retrospective chart reviews extracted history, diagnoses (current and past), and medication treatment. Patients who had discharge diagnoses of bipolar disorder, major depression with psychotic features, or postpartum psychosis were included. Forty-seven met the diagnostic inclusion criteria. Over an average length of stay (ALOS) of 9.96 days, there was significant improvement in depressive and anxiety symptoms and daily functioning (Work and Social Adjustment Scale). Psychiatric comorbidity was common. Polypharmacy was utilized in 87 %. The most common medications prescribed at discharge were antipsychotics, alone or in combination with mood stabilizers or antidepressants. ECT was performed in 10 % of cases. The complexity of patients with severe mood disorders or psychosis admitted to the PPIU supports individualized treatment plans that address both primary diagnosis and psychiatric comorbidities. Our results provide important information that can be disseminated to others to improve clinical outcomes for severe perinatal mood disorders.

Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study.

BACKGROUND: Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. METHOD: We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11-12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. RESULTS: Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53-3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89-6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72-8.50). CONCLUSIONS: We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation.

Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis.

We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6-12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy.

Autophagy of mucin granules contributes to resolution of airway mucous metaplasia.

Exacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations.

Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Repetitive transcranial magnetic stimulation for the treatment of postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a common and gravely disabling health concern. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depression and may be a valuable tool in the treatment of PPD. The treatment effect of rTMS is rapid, generally well tolerated, without systemic effects, and without medication exposure to a fetus and/or breastfed infant. METHODS: Six women with PPD received 20 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) over a 4 week period. Psychiatric rating scales (BDI, EPDS, STATI), cognitive assessments (MMSE, Trails B, List Generation) and breastfeeding practices were surveyed at baseline and post rTMS treatment. BDI and EPDS were obtained weekly, as well as 3 months and 6 months post study conclusion. RESULTS: Average BDI, EPDS, and STAI scores declined over the 4-week duration of rTMS treatment. Of the six patients, four achieved remission as assessed by EPDS and one achieved remission and two responded as assessed by BDI. Mean BDI and EPDS scores at 3 and 6 months follow-up remained below levels at study entry. No evidence of cognitive changes or breastfeeding disruptions. LIMITATIONS: This was an exploratory study with small sample size with no sham control arm. Daily administration of rTMS provides potential for confounding of behavioral activation in the otherwise often isolative postpartum period. CONCLUSIONS: rTMS was safe and well tolerated among participants with evidence of sustained improvements in depression and anxiety scores. This study supports rTMS as a promising non-pharmacologic treatment modality for perinatal depression.

Evolutionary conservation of a microbody targeting signal that targets proteins to peroxisomes, glyoxysomes, and glycosomes.

Peroxisomes, glyoxysomes, glycosomes, and hydrogenosomes have each been classified as microbodies, i.e., subcellular organelles with an electron-dense matrix that is bound by a single membrane. We investigated whether these organelles might share a common evolutionary origin by asking if targeting signals used for translocation of proteins into these microbodies are related. A peroxisomal targeting signal (PTS) consisting of the COOH-terminal tripeptide serine-lysine-leucine-COOH has been identified in a number of peroxisomal proteins (Gould, S.J., G.-A. Keller, N. Hosken, J. Wilkinson, and S. Subramani. 1989. J. Cell Biol. 108:1657-1664). Antibodies raised to a peptide ending in this sequence (SKL-COOH) recognize a number of peroxisomal proteins. Immunocryoelectron microscopy experiments using this anti-SKL antibody revealed the presence of proteins containing the PTS within glyoxysomes of cells from Pichia pastoris, germinating castor bean seeds, and Neurospora crassa, as well as within the glycosomes of Trypanosoma brucei. Western blot analysis of purified organelle fractions revealed the presence of many proteins containing this PTS in both glyoxysomes and glycosomes. These results indicate that at least one of the signals, and therefore the mechanism, for protein translocation into peroxisomes, glyoxysomes, and glycosomes has been conserved, lending support to a common evolutionary origin for these microbodies. Hydrogenosomes, the fourth type of microbody, did not contain proteins that cross-reacted with the anti-PTS antibody, suggesting that this organelle is unrelated to microbodies.

Circadian rhythms in Neurospora crassa: oligomycin-resistant mutations affect periodicity.

Nuclear mutations conferring resistance to oligomycin, a mitochondrial inhibitor, shorten the period of the circadian conidiation rhythm of Neurospora crassa from the normal 21.5 hours to 18 to 19 hours and slow the linear growth rate by 30 percent. These olir mutations map very close to frq, a locus at which mutations affecting periodicity have been previously obtained. The possibilities are discussed that mitochondria are involved in circadian rhythm generation and that certain period-length mutations affect mitochondrial functions.

Circadian rhythms in neurospora: spatial differences in pyridine nucleotide levels.

A growing colony of a mutant strain of Neurospora crassa had two morphologically distinct areas which were formed as a result of a rhythmic spore-forming (conidiation) process. The total pyridine nucleotide content of these two areas was the same, but the levels of NADH, NADPH, and NADP were lower in the conidiating area, while the NAD level was higher. These biochemical differences in the adjacent areas of a single colony were only found in newly formed areas, and were not a permanent record. It is not known whether these pyridine nucleotide changes are a result of the conidiation process, or whether they are tied more directly to some underlying metabolic oscillation. However, it is speculated that the changes in the levels of these key coenzymes could have far-reaching effects on many areas of metabolism.

Overestimation of heterosexually attributed AIDS deaths is associated with immature psychological defence mechanisms and clitoral masturbation during penile-vaginal intercourse.

Research shows that (1) greater use of immature psychological defence mechanisms (associated with psychopathology) is associated with lesser orgasmic consistency from penile-vaginal intercourse (PVI), but greater frequency of other sexual behaviours and greater condom use for PVI, and (2) unlike the vectors of receptive anal intercourse and punctures, HIV acquisition during PVI is extremely unlikely in reasonably healthy persons. However, the relationship between overestimation of AIDS deaths due to 'heterosexual transmission' (often misunderstood as only PVI), sexual behaviour and mental health has been lacking. Two hundred and twenty-one Scottish women completed the Defense Style Questionnaire, reported past month frequencies of their various sexual activities, and estimated the total number of women who died from AIDS in Scotland nominally as a result of heterosexual transmission in the UK from a partner not known to be an injecting drug user, bisexual or infected through transfusion. The average respondent overestimated by 226,000%. Women providing lower estimates were less likely to use immature psychological defences, and had a lower frequency of orgasms from clitoral masturbation during PVI and from vibrator use. The results indicate that those who perceive 'heterosexual transmission' led to many AIDS deaths have poorer psychological functioning, and might be less able to appreciate PVI.