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.

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.

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.

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.

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.

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.

Selective dietary supplementation in early postpartum is associated with high resilience against depressed mood.

Medical research is moving toward prevention strategies during prodromal states. Postpartum blues (PPB) is often a prodromal state for postpartum depression (PPD), with severe PPB strongly associated with an elevated risk for PPD. The most common complication of childbearing, PPD has a prevalence of 13%, but there are no widespread prevention strategies, and no nutraceutical interventions have been developed. To counter the effects of the 40% increase in monoamine oxidase A (MAO-A) levels that occurs during PPB, a dietary supplement kit consisting of monoamine precursor amino acids and dietary antioxidants was created. Key ingredients (tryptophan and tyrosine) were shown not to affect their total concentration in breast milk. The aim of this open-label study was to assess whether this dietary supplement reduces vulnerability to depressed mood at postpartum day 5, the typical peak of PPB. Forty-one healthy women completed all study procedures. One group (n = 21) received the dietary supplement, composed of 2 g of tryptophan, 10 g of tyrosine, and blueberry juice with blueberry extract. The control group (n = 20) did not receive any supplement. PPB severity was quantitated by the elevation in depressed mood on a visual analog scale following the sad mood induction procedure (MIP). Following the MIP, there was a robust induction of depressed mood in the control group, but no effect in the supplement group [43.85 ± 18.98 mm vs. 0.05 ± 9.57 mm shift; effect size: 2.9; F(1,39) = 88.33, P < 0.001]. This dietary supplement designed to counter functions of elevated MAO-A activity eliminates vulnerability to depressed mood during the peak of PPB.

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.

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.

The early care environment and DNA methylome variation in childhood.

Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.

The role of breastfeeding in the association between maternal and infant cortisol attunement in the first postpartum year.

AIM: To explore the role of breastfeeding as a possible link between maternal and infant cortisol attunement across the first postpartum year. METHODS: Mothers (n = 93) provided salivary samples for cortisol levels over a two-day period during mid-pregnancy and at three, six and 12 months and infants at six and 12 months postpartum. Breastfeeding status was established at these same time points. RESULTS: Among breastfeeding mothers, positive correlations were found between maternal cortisol levels during pregnancy and at three months postpartum and infant cortisol at six or 12 months postpartum. Among nonbreastfeeding mothers, these same maternal and infant cortisol relations were inverse and less pronounced. Further, in breastfeeding mothers, the relationship between maternal prenatal cortisol and infant cortisol at 12 months was mediated through maternal cortisol at three months postpartum. CONCLUSION: These results suggest that maternal cortisol levels are positively associated with cortisol levels of the infant, among mothers who breastfeed. This relationship persists over a one-year period.

Fetal growth interacts with multilocus genetic score reflecting dopamine signaling capacity to predict spontaneous sugar intake in children.

BACKGROUND: We have shown that intrauterine growth restriction (IUGR) leads to increased preference for palatable foods at different ages in both humans and rodents. In IUGR rodents, altered striatal dopamine signaling associates with a preference for palatable foods. OBJECTIVES: Our aim was to investigate if a multilocus genetic score reflecting dopamine-signaling capacity is differently associated with spontaneous palatable food intake in children according to the fetal growth status. METHODS: 192 four-year old children from a community sample from Montreal and Hamilton, Canada, were classified according to birth weight and administered a snack test meal containing regular as well as palatable foods. Intrauterine growth restriction was based on the birth weight ratio below 0.85; children were genotyped for polymorphisms associated with dopamine (DA) signaling, with the hypofunctional variants (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10-repeat, Met/Met-COMT) receiving the lowest scores, and a composite score was calculated reflecting the total number of the five genotypes. Macronutrient intake during the Snack Test was the outcome. RESULTS: Adjusting for z-score BMI at 48 months and sex, there was a significant interaction of the genetic profile and fetal growth on sugar intake [߈ = -4.56, p = 0.04], showing a positive association between the genetic score and sugar intake in IUGR children, and no association in non-IUGR children. No significant interactions were seen in other macronutrients. CONCLUSIONS: Variations in a genetic score reflecting DA signaling are associated with differences in sugar intake only in IUGR children, suggesting that DA function is involved in this behavioral feature in these children. This may have important implications for obesity prevention in this population.

Iron Deficiency and Risk of Maternal Depression in Pregnancy: An Observational Study.

OBJECTIVE: Maternal depression during pregnancy can affect both the mother and her family. Although research has suggested that iron deficiency is associated with depression in the general population, this link has not been examined during the antenatal period. Our objective was to determine whether iron deficiency is associated with maternal depression during middle to late pregnancy. METHODS: A retrospective study was conducted using the medical records of patients seen at the Women's Health Concerns Clinic at St. Joseph's Healthcare Hamilton in Hamilton, Ontario between 2009 and 2016. Women with serum ferritin data during middle to late pregnancy (>20 weeks' gestation) (N = 142) were categorized as either iron deficient (ferritin <12 µg/L) or iron sufficient. Edinburgh Postnatal Depression Scale (EPDS) scores and the odds of developing antenatal depression (EPDS ≥12) between the two groups were compared. RESULTS: Iron deficient pregnant women scored significantly higher on the EPDS (10.14 ± 5.69 vs. 7.87 ± 5.75; P = 0.03) and were more likely to develop antenatal depression (45% vs. 25%; P = 0.02) compared with women who were not. The odds of developing antenatal depression were two and one half times higher among iron deficient women (adjusted OR 2.51; 95% CI 1.14-5.52). CONCLUSION: These findings suggest that iron deficiency is associated with higher levels of depression during pregnancy. Although these results require replication, iron deficiency may be an important risk factor for maternal depression during pregnancy.

Executive function in teen and adult women: Association with maternal status and early adversity.

The aim of this study was to determine the impact of maternal age on executive function and the moderating effects of women's maternal status and early-life experiences. Four groups of women were assessed as a function of their age (teens vs. adults) and maternal status (mothers vs. nonmothers). Participants completed executive function tests, including Spatial Working Memory (SWM), Intra-Extra-Dimensional-Set-Shift (IED), and Stockings of Cambridge (SOC). Women also completed the Childhood Trauma Questionnaire to assess their experiences of early adversity. Results showed that for the IED-task, there were main effects of age and maternal status and an interaction between the two; adults performed better than teens, mothers performed better than nonmothers, and teen nonmothers performed the least well of all groups. For the SWM-task, adults performed better than teens. Our results indicate that although age is an important factor for proper executive functioning, different tasks are affected differently and other factors such as maternity and adverse childhood experiences moderate this functioning.

An Attachment-Based Model of the Relationship Between Childhood Adversity and Somatization in Children and Adults.

OBJECTIVE: An attachment model was used to understand how maternal sensitivity and adverse childhood experiences are related to somatization. METHODS: We examined maternal sensitivity at 6 and 18 months and somatization at 5 years in 292 children in a longitudinal cohort study. We next examined attachment insecurity and somatization (health anxiety, physical symptoms) in four adult cohorts: healthy primary care patients (AC1, n = 67), ulcerative colitis in remission (AC2, n = 100), hospital workers (AC3, n = 157), and paramedics (AC4, n = 188). Recall of childhood adversity was measured in AC3 and AC4. Attachment insecurity was tested as a possible mediator between childhood adversity and somatization in AC3 and AC4. RESULTS: In children, there was a significant negative relationship between maternal sensitivity at 18 months and somatization at age 5 years (B = -3.52, standard error = 1.16, t = -3.02, p = .003), whereas maternal sensitivity at 6 months had no significant relationship. In adults, there were consistent, significant relationships between attachment insecurity and somatization, with the strongest findings for attachment anxiety and health anxiety (AC1, ß = 0.51; AC2, ß = 0.43). There was a significant indirect effect of childhood adversity on physical symptoms mediated by attachment anxiety in AC3 and AC4. CONCLUSIONS: Deficits in maternal sensitivity at 18 months of age are related to the emergence of somatization by age 5 years. Adult attachment insecurity is related to somatization. Insecure attachment may partially mediate the relationship between early adversity and somatization.

Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology of Obsessive-Compulsive Disorder: A Critical Review.

Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric disorder affecting between 1.6 and 3.2% of the population. A number of studies have previously reported increased incidence of OCD, or exacerbation of preexisting symptoms in females during reproductive events. Since these periods are known to involve fluctuating levels of gonadal hormones, these steroids have been suggested to be involved in modulating the course of the disorder. However, to date, only a few studies have measured hormone levels and obsessive-compulsive (OC) symptoms concurrently; thus, direct evidence for this relationship is limited. In turn, investigations into neurotransmission in OC individuals have been more extensive, and have implicated the serotonergic, dopaminergic, and glutamatergic neurotransmitter systems in OCD pathology. There is evidence suggesting that reproductive hormones estrogens and progesterone can modulate neurotransmission in the aforementioned signaling pathways by regulating the expression of receptors and channels, as well as the synthesis and release of the neurotransmitter itself. Overall, estrogen and progesterone appear to enhance serotonin signaling, which has been associated with improved OC symptoms. The effect of the gonadal hormones in dopaminergic and glutamatergic signaling is much more variable, highlighting the need for further research in this field. The existing evidence shows that gonadal hormones can have profound impacts on neurotransmission in the brain, leading to the conclusion that the hormonal fluctuations during reproductive events are a plausible factor contributing to the change in OCD course during these times.

A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children.

BACKGROUND: Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk. METHOD: The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed. RESULTS: In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort. CONCLUSIONS: Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results.

Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months.

Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother-infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire-Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis-stress model at 36 months.

The Drosophila foraging gene human orthologue PRKG1 predicts individual differences in the effects of early adversity on maternal sensitivity.

There is variation in the extent to which childhood adverse experience affects adult individual differences in maternal behavior. Genetic variation in the animal foraging gene, which encodes a cGMP-dependent protein kinase, contributes to variation in the responses of adult fruit flies, Drosophila melanogaster, to early life adversity and is also known to play a role in maternal behavior in social insects. Here we investigate genetic variation in the human foraging gene (PRKG1) as a predictor of individual differences in the effects of early adversity on maternal behavior in two cohorts. We show that the PRKG1 genetic polymorphism rs2043556 associates with maternal sensitivity towards their infants. We also show that rs2043556 moderates the association between self-reported childhood adversity of the mother and her later maternal sensitivity. Mothers with the TT allele of rs2043556 appeared buffered from the effects of early adversity, whereas mothers with the presence of a C allele were not. Our study used the Toronto Longitudinal Cohort (N=288 mother-16 month old infant pairs) and the Maternal Adversity and Vulnerability and Neurodevelopment Cohort (N=281 mother-18 month old infant pairs). Our findings expand the literature on the contributions of both genetics and gene-environment interactions to maternal sensitivity, a salient feature of the early environment relevant for child neurodevelopment.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section on "Special Populations" is the sixth of six guidelines articles. RESULTS: Recent studies inform the treatment of MDD in children and adolescents, pregnant and breastfeeding women, women in perimenopause or menopause, and the elderly. Evidence for efficacy of treatments in these populations is more limited than for the general adult population, however, and risks of treatment in these groups are often poorly studied and reported. CONCLUSIONS: Despite the limited evidence base, extant data and clinical experience suggest that each of these special populations can benefit from the systematic application of treatment guidelines for treatment of MDD.