Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems.

Dysregulation is a combination of emotion, behavior, and attention problems associated with lifelong psychiatric comorbidity. There is evidence for the stability of dysregulation from childhood to adulthood, which would be more fully characterized by determining the likely stability from infancy to childhood. Early origins of dysregulation can further be validated and contextualized in association with environmental and biological factors, such as prenatal stress and polygenic risk scores (PRS) for overlapping child psychiatric problems. We aimed to determine trajectories of dysregulation from 3 months to 5 years (N = 582) in association with maternal prenatal depression moderated by multiple child PRS (N = 232 pairs with available PRS data) in a prenatal cohort. Mothers reported depression symptoms at 24-26 weeks' gestation and child dysregulation at 3, 6, 18, 36, 48, and 60 months. The PRS were for major depressive disorder, attention deficit hyperactivity disorder, cross disorder, and childhood psychiatric problems. Covariates were biological sex, maternal education, and postnatal depression. Analyses included latent classes and regression. Two dysregulation trajectories emerged: persistently low dysregulation (94%), and increasingly high dysregulation (6%). Stable dysregulation emerged at 18 months. High dysregulation was associated with maternal prenatal depression, moderated by PRS for child comorbid psychiatric problems. Males were at greater risk of high dysregulation.

Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Emotion regulation moderates between maternal adverse childhood experiences (ACEs) and oxytocin response.

Exposure to adverse childhood experiences (ACEs) is associated with oxytocin dysregulation in women, such as decreased peripheral oxytocin concentrations, but little is known about vulnerability markers for oxytocin dysregulation in mothers exposed to ACEs. Identifying vulnerability markers may help inform future targets for prevention and intervention programmes. This study provided a preliminary examination of emotion regulation as a potential moderator of the association between maternal ACEs and peripheral oxytocin levels. The current study included a sample of 38 postpartum women. Women completed questionnaires on exposure to ACEs and difficulties with emotion regulation. At a clinic visit at 9 months postpartum, women provided plasma and salivary oxytocin samples anchored around a mother-infant interaction. Associations between maternal ACEs, three dimensions of difficulties with emotion regulation, and peripheral oxytocin concentrations were examined. Linear regression analyses showed that greater difficulties engaging in goal-directed behaviour (ß = - 0.50, p = 0.01) and more limited access to effective emotion regulation strategies (ß = - 0.68, p < 0.001) were related to reduced plasma oxytocin concentrations in postpartum women. Furthermore, in postpartum women reporting greater exposure to ACEs, higher levels of nonacceptance of emotional responses (ß = - 0.55, p = 0.01) and more limited access to effective emotion regulation strategies (ß = - 0.54, p = 0.01) were associated with reduced salivary oxytocin response (i.e. decreased change in oxytocin concentrations from baseline) following mother-infant interaction. Difficulties with emotion regulation may serve as a vulnerability marker for oxytocin dysregulation in postpartum women exposed to ACEs, and this suggests that emotion regulation may be an important target for future clinical interventions. Future research is recommended which replicates these preliminary results and which examines how emotion regulation and peripheral oxytocin levels in mothers exposed to ACEs are associated with parenting and child development outcomes.

The Interplay Between Prenatal Adversity, Offspring Dopaminergic Genes, and Early Parenting on Toddler Attentional Function.

Background: Few studies have explored the complex gene-by-prenatal environment-by-early postnatal environment interactions that underlie the development of attentional competence. Here, we examined if variation in dopamine-related genes interacts with prenatal adversity to influence toddler attentional competence and whether this influence is buffered by early positive maternal behavior. Methods: From the Maternal Adversity, Vulnerability and Neurodevelopment cohort, 134 participants (197 when imputing missing data) had information on prenatal adversity (prenatal stressful life events, prenatal maternal depressive symptoms, and birth weight), five dopamine-related genes (DAT1, DRD4, DRD2, COMT, BDNF), observed maternal parenting behavior at 6 months and parent-rated toddler attentional competence at 18 and 24 months. The Latent Environmental and Genetic Interaction (LEGIT) approach was used to examine genes-by-prenatal environment-by-postnatal environment interactions while controlling for sociodemographic factors and postnatal depression. Results: Our hypothesis of a three-way interaction between prenatal adversity, dopamine-related genes, and early maternal parenting behavior was not confirmed. However, consistent two-way interactions emerged between prenatal adversity and dopamine-related genes; prenatal adversity and maternal parenting behavior, and dopamine-related genes and maternal parenting behavior in relation to toddler attentional competence. Significant interaction effects were driven by the DAT1, COMT, and BDNF genotypes; prenatal stressful life events; maternal sensitivity, tactile stimulation, vocalization, and infant-related activities. Conclusions: Multiple dopamine-related genes affected toddler attentional competence and they did so in interaction with prenatal adversity and the early rearing environment, separately. Effects were already visible in young children. Several aspects of early maternal parenting have been identified as potential targets for intervention.

Maternal Prenatal Mood, Pregnancy-Specific Worries, and Early Child Psychopathology: Findings From the DREAM BIG Consortium.

OBJECTIVE: Few studies have attempted to identify how distinct dimensions of maternal prenatal affective symptoms relate to offspring psychopathology. We defined latent dimensions of women's prenatal affective symptoms and pregnancy-specific worries to examine their association with early offspring psychopathology in three prenatal cohorts. METHOD: Data were used from three cohorts of the DREAM-BIG consortium: Avon Longitudinal Study of Parents and Children (ALSPAC [N = 12,515]), Generation R (N = 6,803), and the Canadian prenatal cohort Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN [N = 578]). Maternal prenatal affective symptoms and pregnancy-specific worries were assessed using different measures in each cohort. Through confirmatory factor analyses, we determined whether comparable latent dimensions of prenatal maternal affective symptoms existed across the cohorts. We used structural equation models to examine cohort-specific associations between these dimensions and offspring psychopathology at 4 to 8 years of age (general psychopathology, specific internalizing and externalizing previously derived using confirmatory factor analyses). Cohort-based estimates were meta-analyzed using inverse variance-weighing. RESULTS: Four prenatal maternal factors were similar in all cohorts: a general affective symptoms factor and three specific factors-an anxiety/depression factor, a somatic factor, and a pregnancy-specific worries factor. In meta-analyses, both the general affective symptoms factor and pregnancy-specific worries factor were independently associated with offspring general psychopathology. The general affective symptoms factor was further associated with offspring specific internalizing problems. There were no associations with specific externalizing problems. CONCLUSION: These replicated findings of independent and adverse effects for prenatal general affective symptoms and pregnancy-specific worries on child mental health support the need for specific interventions in pregnancy.

Obsessive-compulsive and related disorders.

Obsessive-compulsive and related disorders (OCRDs), sometimes referred to as obsessive-compulsive spectrum disorders, cause significant impairment and share similar features across several domains, including clinical course, risk factors, and response to treatment. Generally, individuals meeting criteria for one or more OCRDs present with symptoms focused on preoccupations and repetitive behaviors. Sex differences emerge in the clinical presentation of OCRDs, and the associated. Literature emphasizes the importance of considering sex when investigating causal factors, prognosis, and outcomes of OCRDs. Understanding sex-specific phenotypes can help clinicians and healthcare providers to screen for and recognize relevant symptoms, and to create a more tailored approach for care of males and females. In this chapter, we review sex differences in obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder, trichotillomania (hair-pulling disorder), and excoriation (skin-picking) disorder. Here, we provide an updated review on the sex differences in the prevalence, symptomatology, illness course and prognosis, comorbidity, risk factors, and treatment outcomes associated with OCRDs, and highlight gaps in the current literature on sex differences in these disorders.

The association of HTR2A polymorphisms with obsessive-compulsive disorder and its subtypes: A meta-analysis.

BACKGROUND: Genetic risk factors that contribute to obsessive-compulsive disorder (OCD) have yet to be elucidated. Historically, serotonergic dysfunction has been implicated. Evidence from the literature points towards the serotonin receptor 2A gene (HTR2A) as a primary candidate. Our meta-analysis investigated whether polymorphisms in HTR2A are associated with OCD or its subtypes, based on sex and age of onset. METHODS: Studies employing case-control or family-based designs were systematically searched, and those meeting eligibility underwent quality assessment, resulting in 18 studies. A random-effects meta-analysis using standard inverse-variance weighting to compute odds ratio (OR) was conducted. To examine sensitivity, results were also obtained using a more conservative statistical method. RESULTS: Three HTR2A variants were identified: T102C, G-1438A, and C516T. T102C and G-1438A were analyzed together due to strong linkage disequilibrium, where the 102T allele co-occurs with -1438A allele. Results reported as OR [95%CI] showed that the T/A allele were significantly associated with OCD, 1.14 [1.01, 1.29]. After stratification, results remained significant for females, 1.20 [1.00, 1.45], and early-onset OCD, 1.27 [1.02, 1.58], but not males, 1.06 [0.91, 1.23]. No associations were found for late-onset OCD, 0.98 [0.70, 1.37], or C516T, 1.22 [0.14, 10.37], but conclusions cannot be drawn from two studies. LIMITATIONS: Associations no longer reached significance with the conservative statistical approach. HTR2A alone cannot explain OCD complexity and limited samples reporting genetic data according to subtypes. CONCLUSIONS: These results suggest a possible association of HTR2A polymorphisms with OCD, but further investigations considering sex and age of onset with larger samples is needed.

Pregnancy and Delivery Outcomes Following Benzodiazepine Exposure: A Systematic Review and Meta-analysis.

OBJECTIVE: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. DATA SOURCES: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. STUDY SELECTION: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. DATA EXTRACTION: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. RESULTS: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. CONCLUSIONS: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.

Maternal symptoms of depression and sensitivity mediate the relation between maternal history of early adversity and her child temperament: The inheritance of circumstance.

We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother-child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of "negative emotionality/behavioral dysregulation" was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Once and Again : History of Rearing Experiences and Psychosocial Parenting Resources at Six Months in Primiparous Mothers.

Animal and human studies suggest that parenting style is transmitted from one generation to the next. The hypotheses of this study were that (1) a mother's rearing experiences (G1) would predict her own parenting resources (G2) and (2) current maternal mood, motivation to care for her offspring, and relationship with her parents would underlie this association. In a subsample of 201 first-time mothers participating in the longitudinal Maternal Adversity, Vulnerability and Neurodevelopment project, we assessed a mother's own childhood maltreatment and rearing experiences (G1) using the Childhood Trauma Questionnaire and the Parental Bonding Instrument. At 6 months postpartum, mothers completed questionnaires on parenting stress (G2), symptoms of depression, maternal motivation, and current relationship with their own parents. The sample consisted of mostly high socioeconomic status mothers recruited from Montréal (n = 135) or Hamilton (n = 66), Canada, with an age range from 18 to 43 years (M = 29.41, SD = 4.85 years). More severe maltreatment and less supportive rearing by the mother's parents (G1) predicted increased parenting stress at 6 months (G2). These associations were mediated through distinct psychosocial pathways: maltreatment (G1) on parenting stress (G2) through symptoms of depression (Z = 2.297; p = .022); maternal rearing (G1) on parenting stress (G2) through maternal motivation (Z = -2.155; p = .031) and symptoms of depression (Z = -1.842; p = .065); and paternal rearing (G1) on parenting stress (G2) through current relationship with the father (Z = -2.617; p = .009). Maternal rearing experiences predict a mother's own parenting resources though distinct psychosocial pathways, including depressed mood, maternal motivation, and social support.

Amygdala and affective responses to infant pictures: Comparing depressed and non-depressed mothers and non-mothers.

In many mammalian species, new mothers show heightened positive responsiveness to infants and their cues when they give birth. As is evident from non-human and human studies, the amygdala is a brain region implicated in both the maternal and affective neural circuitry, and is involved in processing socioemotionally salient stimuli. In humans, infants are socially salient stimuli to women, and mothers in particular. Neuroimaging studies investigating the maternal response to infant cues have identified infant-related amygdala function as an important factor in maternal anxiety/depression, in the quality of mothering and in individual differences in the motivation to mother. The present study investigated the effects of maternal status and depression on the subjective affective response and amygdala responsiveness to unfamiliar infants using functional magnetic resonance imaging. Smiling infant pictures were used in a 2 × 2 design comparing four groups of women: mothers and non-mothers, with and without depression (total of 101 women: postpartum depression [PPD] = 32, non-PPD = 25, major depression [MDD] = 15, non-MDD = 29). We undertook an anatomically defined region of interest analysis of the amygdala response for a priori defined group comparisons. We found that mothers rated infants more positively than non-mothers and non-mothers rated non-infant stimuli (scenery) more positively than mothers. In the amygdala, we found that depression elevated response to smiling unfamiliar infants in mothers but had no effect in non-mothers. Within the depressed groups, mothers (PPD) showed an elevated amygdala response to unfamiliar smiling infants compared to depressed non-mothers. Hence, our results indicate that women with PPD show an enhanced amygdala response to affectively positive infant pictures but not to affectively positive (but non-salient) pictures of scenery. Women with depression outside of the postpartum period show no change in amygdala responsiveness to either stimulus categories.

Dissecting maternal care: Patterns of maternal parenting in a prospective cohort study.

Parental care has a strong impact on neurodevelopment and mental health in the offspring. Although numerous animal studies have revealed that the parental brain is a highly complex system involving many brain structures and neuroendocrine systems, human maternal parenting as a multidimensional construct with cognitive, emotional, and behavioural components has not been characterised comprehensively. This unique multi-method analysis aimed to examine patterns of self-reported and observed parenting from 6 to 60 months postpartum in a cohort of 496 mothers (mean maternal age = 32 years). Self-report questionnaires assessed motivational components of mothering, parenting stress, parenting-related mood, maternal investment, maternal parenting style, mother-child relationship satisfaction, and mother-child bonding at multiple time points. Observed parenting variables included the Ainsworth Sensitivity Scales at 6 and 18 months, the Behavioral Evaluation Strategies Taxonomies at 6 months, an Etch-A-Sketch cooperation task at 48 months, and the Parent-Child Early Relationship Assessment at 60 months. To examine whether different latent constructs underlie these measures of maternal parenting, we conducted an exploratory factor analysis. Self-report measures of parenting correlated only weakly with behavioural observations. Factor analysis on a subsample (n = 197) revealed four latent factors that each explained from 7% to 11% of the variance in the data (32% total variance explained). Based on the loadings of the instruments, the factors were interpreted as: Supportive Parenting, Self-Enjoyment Parenting, Overwhelmed Parenting, and Affectionate Parenting. These factor scores showed specific associations with maternal education and depressive symptoms, as well as with child outcomes, including maternally reported internalising and externalising behavioural problems, school readiness, and child-reported symptoms of mental health. These findings parallel the complexity of the parental brain, suggesting that maternal parenting consists of multiple components, each of which is associated with different maternal characteristics and child outcomes.

Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations. DATA SOURCES: MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation). STUDY SELECTION: English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included. DATA EXTRACTION: Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others. RESULTS: Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies). CONCLUSIONS: Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.

General psychopathology, internalising and externalising in children and functional outcomes in late adolescence.

BACKGROUND: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. METHODS: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. RESULTS: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. CONCLUSIONS: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact.

Inflammation, depression and cardiovascular disease in women: the role of the immune system across critical reproductive events.

Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient's reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women's health.

Alternating optimization for G × E modelling with weighted genetic and environmental scores: Examples from the MAVAN study.

Motivated by the goal of expanding currently existing Genotype × Environment interaction (G × E) models to simultaneously include multiple genetic variants and environmental exposures in a parsimonious way, we developed a novel method to estimate the parameters in a G × E model, where G is a weighted sum of genetic variants (genetic score) and E is a weighted sum of environments (environmental score). The approach uses alternating optimization, an iterative process where the genetic score weights, the environmental score weights, and the main model parameters are estimated in turn, assuming the other parameters are constant. This technique can be used to construct relatively complex interaction models that are constrained to a particular structure, and hence contain fewer parameters. We present the model as a 2-way interaction longitudinal mixed model, for which ordinary linear regression is a special case, but it can easily be extended to be compatible with k-way interaction models and generalized linear mixed models. The model is implemented in R (LEGIT package) and using SAS macros (LEGIT_SAS). Through simulations, we demonstrate the power and validity of this approach even with small sample sizes. Furthermore, we present examples from the Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study where we improve significantly upon already existing models using alternating optimization. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A systematic review and meta-analysis of the effects of antenatal anxiety on postpartum outcomes.

To systematically review and meta-analyze research investigating the association between maternal anxiety during pregnancy and outcomes for mother and baby following the immediate delivery period. MEDLINE, Medline In-Process & Other Non-Indexed Citations, PsycINFO, Embase, CINAHL, and the Cochrane library were searched. English-language, prospective studies providing data on outcomes following delivery in women with and without antenatal anxiety (defined by clinical diagnosis or score on validated scale) were included. Three-hundred-fifty-eight articles were retrieved and 13 were included. Titles and abstracts were screened; two reviewers independently reviewed full text articles, conducted quality assessments, extracted, and checked the data. Where available for > 2 studies, random effect meta-analysis was conducted and heterogeneity was quantified. Subanalyses explored moderators, regardless of heterogeneity, including type of anxiety assessment and timing, among others. There were two outcomes that were amenable to meta-analysis. Antenatal anxiety was significantly associated with postpartum depression (PPD) measured within 6 months postpartum (pooled odds ratio [OR] = 2.64, 95% CI 2.02-3.46; 8 studies), regardless of restricting analyses to those studies controlling for prenatal depression (2.45, 1.77-3.39; 6 studies). Associations were also significant when PPD was measured at 1-3 months (2.57, 1.94-3.40; 7 studies) and 6-10 months (4.42, 1.45-13.49; 3 studies). Maternal anxiety was also associated with reduced odds of breastfeeding (0.63, 0.53-0.74; 5 studies). Antenatal anxiety is associated with PPD up to the first 10 months, independent of prenatal depression, and with lower odds of breastfeeding.

Maternal perceptions of paternal investment are associated with relationship satisfaction and breastfeeding duration in humans.

This study examined potential pathways in the associations between breastfeeding and mothers' relationship satisfaction, including her satisfaction with father involvement (FI) and parity, among mothers not working outside the home at 6 months. Mothers (n = 222) completed questionnaires at 4 time-points, 3 to 24 months postpartum as part of a longitudinal cohort study. In this study, we were interested in two main outcome variables: mothers' relationship satisfaction with their partner (RS) and continuation of breastfeeding after 3 months. Our first analysis revealed that breastfeeding at 3 months postpartum predicted decreased RS at 6 months postpartum, which was mediated by mothers' dissatisfaction with FI in infant caretaking at 6 months postpartum. These associations depended on mothers' parity: Multiparous breastfeeding mothers were the most dissatisfied with FI. Second, mothers' satisfaction with FI at 6 months also predicted increased RS at 24 months through increased RS at 12 months, but not through FI at 18 months. Third, we found that high dissatisfaction with FI at 6 months was the only significant predictor for the discontinuation of breastfeeding from 3 to 6 months postpartum. Our results suggest that multiparous breastfeeding mothers might be more dissatisfied with FI in caregiving than nonbreastfeeding mothers and primiparous breastfeeding mothers. Furthermore, mothers' satisfaction with FI seems a potent predictor of overall RS up to 24 months postpartum and the continuation of breastfeeding from 3 to 6 months postpartum, regardless of parity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Uninterrupted Infant Sleep, Development, and Maternal Mood.

OBJECTIVES: Contrary to the importance of total sleep duration, the association between sleeping through the night and development in early infancy remains unclear. Our aims were to investigate the proportion of infants who sleep through the night (6- or 8-hour sleep blocks) at ages 6 and 12 months in a longitudinal cohort and to explore associations between sleeping through the night, mental and psychomotor development, maternal mood, and breastfeeding. METHODS: At 6 and 12 months of age, maternal reports were used to assess the longest period of uninterrupted infant sleep and feeding method (n = 388). Two different criteria were used to determine if infants slept through the night: 6 and 8 hours of uninterrupted sleep. Mental and psychomotor developmental indices (Bayley Scales of Infant Development II) and maternal mood (Center for Epidemiologic Studies Depression Scale) were measured at 6, 12, and 36 months of age. RESULTS: Using a definition of either 6 or 8 hours of uninterrupted sleep, we found that 27.9% to 57.0% of 6- and 12-month-old infants did not sleep through the night. Linear regressions revealed no significant associations between sleeping through the night and concurrent or later mental development, psychomotor development, or maternal mood (P > .05). However, sleeping through the night was associated with a much lower rate of breastfeeding (P < .0001). CONCLUSIONS: Considering that high proportions of infants did not sleep through the night and that no associations were found between uninterrupted sleep, mental or psychomotor development, and maternal mood, expectations for early sleep consolidation could be moderated.