The contribution of prenatal and postnatal maternal anxiety and depression to child maladjustment

Background: The adverse effect of both pre‐ and post‐natal maternal anxiety and depression on the development of offspring is shown by a large body of research. No published studies, however, have simultaneously: (i) controlled for co‐occurring prenatal risks that may influence maternal prenatal anxiety and depression; (ii) compared the relative contributions of prenatal and postnatal maternal anxiety and depression on child functioning; and (iii) assessed a full range of child psychopathology and functioning to determine the relative effects of prenatal and postnatal anxiety and depression in the mother. Method: Using 3,298 mother–offspring pairs, the authors examined these factors in a single‐path analytic model. Measurements of maternal anxiety and depression were collected at two time points: 32 weeks prenatal and 1.5 years postnatal. Other prenatal risks were assessed between 8 and 32 weeks of gestation. Child outcomes included (a) ordered‐categorical measures of DSM‐IV externalizing and internalizing disorders, and (b) an assessment of verbal IQ. Results: In both the prenatal and postnatal periods, maternal depression had a wider impact on different types of child maladjustment than maternal anxiety, which appeared more specific to internalizing difficulties in the child. Of note, prenatal risks were prospectively associated with child externalizing difficulties and verbal IQ, beyond the effects of prenatal and postnatal maternal anxiety and depression. Conclusion: The present results suggest that addressing both maternal anxiety and depression, in the prenatal and postnatal periods—as well as associated risk factors—may be the most effective approach to prevent adverse outcomes in the offspring. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study

OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. METHOD: Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. RESULTS: Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.     

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

BACKGROUND: A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for the development of PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low offspring cortisol prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses in offspring. METHODS: One hundred seventeen men and 167 women, recruited from the community, were evaluated using a comprehensive psychiatric battery designed to identify traumatic life experiences and lifetime psychiatric diagnoses. 211 of these subjects were the adult offspring of Holocaust survivors and 73 were demographically comparable Jewish controls. Participants were further subdivided based on whether their mother, father, neither, or both parents met diagnostic criteria for lifetime PTSD. RESULTS: A higher prevalence of lifetime PTSD, mood, anxiety disorders, and to a lesser extent, substance abuse disorders, was observed in offspring of Holocaust survivors than controls. The presence of maternal PTSD was specifically associated with PTSD in adult offspring of Holocaust survivors. However, other psychiatric diagnoses did not show specific effects associated with maternal PTSD. CONCLUSION: The tendency for maternal PTSD to make a greater contribution than paternal PTSD to PTSD risk suggests that classic genetic mechanisms are not the sole model of transmission, and paves way for the speculation that epigenetic factors may be involved. In contrast, PTSD in any parent contributes to risk for depression, and parental traumatization is associated with increased anxiety disorders in offspring.     

Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent

In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother.     

Epigenetic mechanisms and the transgenerational effects of maternal care

The transmission of traits across generations has typically been attributed to the inheritance by offspring of genomic information from parental generations. However, recent evidence suggests that epigenetic mechanisms are capable of mediating this type of transmission. In the case of maternal care, there is evidence for the behavioral transmission of postpartum behavior from mothers to female offspring. The neuroendocrine and molecular mediators of this transmission have been explored in rats and implicate estrogen-oxytocin interactions and the differential methylation of hypothalamic estrogen receptors. These maternal effects can influence multiple aspects of neurobiology and behavior of offspring and this particular mode of inheritance is dynamic in response to environmental variation. In this review, evidence for the generational transmission of maternal care and the mechanisms underlying this transmission will be discussed as will the implications of this inheritance system for offspring development and for the transmission of environmental information from parents to offspring.     

Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment

Parental stress exposures are implicated in the risk for offspring neurodevelopmental and neuropsychiatric disorders, prompting critical examination of preconception and prenatal periods as vulnerable to environmental insults such as stress. Evidence from human studies and animal models demonstrates the influence that both maternal and paternal stress exposures have in changing the course of offspring brain development. Mechanistic examination of modes of intergenerational transmission of exposure during pregnancy has pointed to alterations in placental signaling, including changes in inflammatory, nutrient-sensing, and epigenetic pathways. Transmission of preconception paternal stress exposure is associated with changes in epigenetic marks in sperm, with a primary focus on the reprogramming of DNA methylation, histone posttranslational modifications, and small noncoding RNAs. In this review, we discuss evidence supporting the important contribution of intergenerational parental stress in offspring neurodevelopment and disease risk, and the currently known epigenetic mechanisms underlying this transmission.     

Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stress‐reactive Wistar Kyoto rats

Early‐life stress (ELS) can alter neurodevelopment in variable ways, ranging from producing deleterious outcomes to stress resilience. While most ELS studies focus on its harmful effects, recent work by our laboratory and others shows that ELS elicits positive effects in certain individuals. We exposed Wistar Kyoto (WKY) rats, known for a stress reactive, anxiety/depression‐like phenotype, to maternal separation (MS), a model of ELS. MS exposure elicited anxiolytic and antidepressant behavioral effects as well as improved cardiovascular function in adult WKY offspring. This study interrogates an epigenetic mechanism (DNA methylation) that may confer the adaptive effects of MS in WKY offspring. We quantified global genome methylation levels in limbic brain regions of adult WKYs exposed to daily 180‐min MS or neonatal handling from postnatal day 1–14. MS exposure triggered dramatic DNA hypermethylation specifically in the hippocampus. Next‐generation sequencing methylome profiling revealed reduced methylation at intragenic sites within two key nodes of insulin signaling pathways: the insulin receptor and one of its major downstream targets, mitogen‐activated protein kinase kinase kinase 5 (Map3k5). We then tested the hypothesis that enhancing DNA methylation in WKY rats would elicit adaptive changes akin to the effects of MS. Dietary methyl donor supplementation improved WKY rats’ anxiety/depression‐like behaviors and also improved cardiovascular measures, similar to previous observations following MS. Overall, these data suggest a potential molecular mechanism that mediates a predicted adaptive response, whereby ELS induces DNA methylation changes in the brain that may contribute to successful stress coping and adaptive physiological changes in adulthood.     

Epigenetic mechanisms mediating the long-term effects of maternal care on development

The long-term consequences of early environmental experiences for development have been explored extensively in animal models to better understand the mechanisms mediating risk of psychopathology in individuals exposed to childhood adversity. One common feature of these models is disruption of the mother-infant relationship which is associated with impairments in stress responsivity and maternal behavior in adult offspring. These behavioral and physiological characteristics are associated with stable changes in gene expression which emerge in infancy and are sustained into adulthood. Recent evidence suggests that these long-term effects may be mediated by epigenetic modification to the promoter regions of steroid receptor genes. In particular, DNA methylation may be critical to maternal effects on gene expression and thus generate phenotypic differentiation of offspring and, through effects on maternal behavior of offspring, mediate the transmission of these effects across generations. In this review we explore evidence for the influence of mother-infant interactions on the epigenome and consider evidence for and the implications of such epigenetic effects for human mental health.     

Behavioral inhibition

Over the past 25 years, our understanding of the risks conferred by "behavioral inhibition to the unfamiliar" (BI) has grown tremendously, yet many questions remain. BI represents the persistent tendency to show extreme reticence, fearfulness, or avoidance in novel situations or with unfamiliar people. Prospective studies of high-risk offspring, selected community children, and unselected epidemiologic samples converge to suggest that BI confers specific risk for social anxiety disorder in early and middle childhood and adolescence. Later outcomes are less clear, with some studies suggesting associations with depression or panic disorder. Studies that find broad associations between BI and anxiety proneness in general may be limited by the absence of information about parental psychopathology (an important potential confound associated with both BI and anxiety disorders in offspring). A critical area for further inquiry is the degree to which BI confers risk for social anxiety disorder in the absence of family history of anxiety disorders. Additionally, although progress has been made in identifying risk factors, protective factors, and treatments that may influence the course of BI and associated anxiety, more work is needed. Also, several exciting inroads have been made into the genetic and neurobiologic underpinnings of BI, and future studies promise greater elucidation of these areas. For now, the clinical take-home message is that preschool-age children presenting with extreme and persistent BI are at elevated risk for social anxiety disorder and possibly for other future disorders; preliminary evidence suggests that these children may be helped by early cognitive-behavioral intervention.     

Age-specific familial risks of depression: a nation-wide epidemiological study from Sweden

OBJECTIVE: Familial risks of depression have been assessed in small case-control studies, usually based on reported, but not medically verified, depressions in family members; thus the degree of familial clustering of these diseases remains to be established. METHODS: The Multigeneration Register, in which all men and women born in Sweden from 1932 onward are registered together with their parents, was linked to hospital admission data. Standardized incidence ratios (SIRs) were calculated as the ratio of the observed to the expected number of cases in men and women with mothers or fathers affected by depression, compared with men and women whose mothers or fathers were not affected by depression. RESULTS: A total of respectively 60,477 and 79,969 depressions were recorded in offspring and parents. In 6.44% of all families, an offspring and a parent were affected, giving a population-attributable proportion of 4.04% and a familial SIR of 2.68. The parental transmission of depression was similar for both men and women (2.72 and 2.66). CONCLUSIONS: This study has provided the first data on age-specific familial clustering of depressions, based on medically confirmed records. The risks were so high that hereditary factors were considered to be likely to contribute to depression, possibly modified by environmental factors. Age-specific risk tables would be helpful for clinical counseling.     

Prenatal psychobiological predictors of anxiety risk in preadolescent children

Experimental animal models have demonstrated that one of the primary consequences of prenatal stress is increased fear and anxiety in the offspring. Few prospective human studies have evaluated the consequences of prenatal stress on anxiety during preadolescence. The purpose of this investigation is to determine the consequences of prenatal exposure to both maternal biological stress signals and psychological distress on anxiety in preadolescent children. Participants included 178 mother-child pairs. Maternal psychological distress (general anxiety, perceived stress, depression and pregnancy-specific anxiety) and biological stress signals were evaluated at 19, 25, and 31 gestational weeks. Anxiety was evaluated in the children at 6-9 years of age using the Child Behavior Checklist. Analyses revealed that prenatal exposure to elevated maternal cortisol, depression, perceived stress and pregnancy-specific anxiety was associated with increased anxiety in children. These associations remained after considering obstetric, sociodemographic and postnatal maternal psychological distress; factors that could influence child development. When all of the prenatal measures were considered together, cortisol and pregnancy-specific anxiety independently predicted child anxiety. Children exposed to elevated prenatal maternal cortisol and pregnancy-specific anxiety were at an increased risk for developing anxiety problems during the preadolescent period. This project identifies prenatal risk factors associated with lasting consequences for child mental health and raises the possibility that reducing maternal distress during the prenatal period will have long term benefits for child well-being.     

Families at high and low risk for depression: a 3-generation study

BACKGROUND: The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort. OBJECTIVE: To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. DESIGN: Longitudinal, retrospective cohort, family study. PARTICIPANTS: One hundred sixty-one grandchildren and their parents and grandparents. MAIN OUTCOME MEASURES: Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews. RESULTS: There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression. CONCLUSIONS: The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.     

Incidence of psychiatric disorder in offspring at high and low risk for depression.

First onsets (incidence) of suicide attempts and DSM-III psychiatric disorders, including major depression, any anxiety disorder, conduct disorder, or substance abuse were determined in a 2-year longitudinal study of 174 offspring at high and low risk for major depression. All of the suicide attempts, the first onsets of major depression, and anxiety disorders were in offspring of depressed parents. Compared with asymptomatic offspring, offspring with subclinical manifestations of major depression, conduct disorder, and substance abuse at the initial interview were significantly more likely to become incident cases of the same disorder over the next 2 years. Either conduct disorder or substance abuse at initial interview were highly predictive of first onset of each other, but not of any other disorders 2 years later. Family risk factors (such as poor marital adjustment, parent-child discord, low cohesion, and affectionless control) at initial interview were associated with increased incidence of substance abuse, or conduct disorder, but not major depression or anxiety disorder. Combining both retrospective and prospective data, the overall suicide attempt rate was 7.8% in the offspring of depressed parents as compared with 1.4% in the offspring of nondepressed parents. By age 20, over 50% of the offspring of depressed patients reported a major depression.     

The Impact of Maternal Adverse Childhood Experiences on Offspring’s Internalizing and Externalizing Problems

ObjectiveAdverse childhood experiences (ACEs) are associated with negative physical and mental health outcomes across the lifespan, but research on intergenerational transmission of maternal ACEs and its impact on the offspring’s mental health problems are limited. The study examines the effects of maternal ACEs on the risk of internalizing or externalizing problems among offspring. MethodsThere were 450 mother-child dyads. Mothers completed the Adverse Childhood Experiences Questionnaire. The child outcomes included internalizing and externalizing problems assessed by the Korean Child Behavior Checklist (K-CBCL) and Korean Youth Self-Report (K-YSR), depression assessed by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) and anxiety assessed by the Screen for Child Anxiety Related Emotional Disorders (SCARED). Results36.1% of mothers experienced at least one ACE, and 11.1% experienced three or more ACEs. Cumulative maternal ACEs were associated with internalizing problems, externalizing problems, depression and anxiety in the offspring. Household dysfunction from maternal ACEs was significantly associated with delinquent behavior, anxiety/depression, and somatic complaints in the offspring. ConclusionThe findings support the hypothesis that maternal ACEs are related to mental health problems in the offspring. Further research is needed to determine the factors mediating intergenerational transmission as well as intervention strategies to prevent ACEs and mental health problems in the offspring.     

Family discord, parental depression, and psychopathology in offspring: ten-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on psychopathology in offspring at high and low risk for major depression. METHOD: One hundred eighty-two offspring of depressed or nondepressed parents were followed over 10 years. In direct interviews, parents' and offspring's psychopathology was evaluated by raters blind to parents' clinical status. Five dimensions of family discord-poor marital adjustment, parent-child discord, low family cohesion, affectionless control, and parental divorce-were assessed. RESULTS: Offspring exposed to either parental depression or family discord had higher rates of psychopathology than their counterparts. High-risk offspring had few family discord measures associated with their psychopathology; in low-risk offspring, family discord was associated with all offspring diagnoses. Between the two risk factors, parental depression proved a more important predictor for offspring major depressive disorder (MDD) and anxiety disorder, whereas family discord was a more important predictor for substance use disorder. CONCLUSIONS: Parental depression is a strong and consistent risk factor for offspring MDD and anxiety disorder. Without parental depression, offspring have less exposure to family discord and lower rates of psychopathology. In the presence of family discord, rates of MDD, anxiety disorder and substance use disorder increased. When offspring matured into young adulthood, effects of parental depression and family discord persisted.     

Maternal inexperience as a risk factor of innate fear and PTSD-like symptoms in mice

In laboratory rats and mice, differences in maternal care during the first week of life have been shown to exert long-lasting consequences on cognitive functioning and stress processing of the offspring. Such epigenetic programming is also assumed to play an important role in the transgenerational transmission of PTSD in humans. Here we studied whether even subtle within-subject differences in maternal care - caused by increasing mothering experience from the first to the second litter - can determine subsequent vulnerability for PTSD-like behaviour. To assess the influence of maternal experience on different components of fear, we analysed the adult male offspring of two subsequent litters (offspring 1, 2) from the same parental C57BL/6NCrl (B6N) and C57BL/6JOla (B6JOla) mice for (i) their innate anxiety behaviour on a modified hole board and (ii) their vulnerability to develop long-lasting PTSD-like fear symptoms (“hyperarousal”, contextually conditioned fear) following perception of an inescapable foot shock. Increasing maternal experience reduced the animals’ innate fear on the modified hole board (more exploration, less inhibition), the acute stress reaction to the shock and - one month after trauma - the levels of hyperarousal-like behaviour in the PTSD-prone B6N strain. In contrast, both acquisition and extinction of contextually conditioned fear were increased in the second offspring, representing cognitive flexibility. A factor analysis showed that innate fear, “hyperarousal” and conditioned fear represent independent behavioural dimensions. In conclusion, the present study identifies maternal inexperience as a risk factor for the development of PTSD-like symptoms. This effect - occurring in inbred mice on an almost identical genetic background - emphasizes the impact of epigenetic factors in PTSD-like behaviour.     

Family discord, parental depression, and psychopathology in offspring: 20-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on offspring psychopathology among children at high and low risk of depression. METHOD: Family discord factors were assessed when subjects were approximately 17 years old, and offspring diagnoses were assessed about 20 years later. Parental and offspring psychopathology was assessed by interviewers blind to parents' clinical status. The following dimensions of family discord were assessed: poor marital adjustment, parent child discord, low family cohesion, affectionless control, and parental divorce. RESULTS: Most family discord factors were associated with parental depression. Among children of depressed parents, none of the measures of family discord had a statistically significant association with offspring major depressive disorder or anxiety disorders. Among children of nondepressed parents, parental affectionless control was associated with an almost fivefold increased risk of major depressive disorder (odds ratio [OR] = 4.8; p < or = .05) and with more than a 14-fold increased risk of substance use disorders (OR = 14.3; p < or = .01). CONCLUSIONS: Parental depression is associated with family discord and is a consistent risk factor for offspring major depressive disorder and anxiety disorders, as shown over a 20-year follow-up of offspring of depressed and nondepressed parents. Family discord factors may be a risk factor for major depressive disorder and substance use disorders in offspring of nondepressed parents.     

The role of parental psychopathology and family environment for social phobia in the first three decades of life

Background: To examine the role of parental psychopathology and family environment for the risk of social phobia (SP) in offspring from childhood to early adulthood, encompassing the high risk period for SP. Methods: A community sample of 1,395 adolescents was prospectively followed‐up over 10 years. Offspring and parental psychopathology were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) using the Munich Composite International Diagnostic Interview (M‐CIDI), and direct diagnostic interviews in parents were supplemented by family history reports. Parental rearing was assessed by the Questionnaire of Recalled Rearing Behavior administered to offspring. Family functioning was assessed by the McMaster Family Assessment Device administered to parents. Results: Parental SP was associated with offspring's risk to develop SP (OR=3.3, 95%CI:1.4–8.0). Other parental anxiety disorders (OR=2.9, 95%CI:1.4–6.1), depression (OR=2.6, 95%CI:1.2–5.4), and alcohol use disorders (OR=2.8, 95%CI:1.3–6.1) were also associated with offspring SP. Parental rearing styles of overprotection, rejection, and lack of emotional warmth were associated with offspring SP. Family functioning measures were not associated with offspring SP. Analyses of interaction of parental psychopathology and parental rearing indicated combined effects on the risk for offspring SP. Conclusions: Parental psychopathology and rearing were associated with offspring SP, independently as well as in their interaction. Further delineation of these associations is warranted as malleable components of these risk factors may provide potential targets for prevention programs. In addition, parent‐to‐offspring transmission of other internalizing disorders should be considered to examine the degree of diagnostic specificity. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Antenatal depression and children’s developmental outcomes: potential mechanisms and treatment options

During the last decade there has been increased recognition of the prevalence of antenatal depression as well as an expansion in research examining the impact of maternal mood during pregnancy on offspring development. The aim of this review was to summarise the theoretical underpinnings and empirical evidence regarding the impact of antenatal depression on children’s developmental outcomes. Biological mechanisms hypothesised to account for an association between antenatal depression and adverse offspring outcomes are first identified including the functioning of the prenatal Hypothalamic Pituitary Adrenal (HPA) axis and epigenetic processes. A systematic literature search is then conducted of studies examining the impact of antenatal depression on child development. In general, studies examining associations between antenatal depression and offspring temperament, cognitive and emotional outcomes reveal either no effect of the prenatal environment or small effects that often attenuate following adjustment for other antenatal and postnatal risk factors. In contrast, an independent effect of antenatal depression on children’s conduct problems and antisocial behaviour is a well-replicated finding. There is emerging evidence that exposure to depression during pregnancy impacts negatively on offspring biology, although the findings are complex and require replication. Psychological and pharmacological treatments of antenatal depression are then reviewed, considering whether antidepressant medication exerts harmful effects on the foetus. We close by proposing that antenatal depression is an early marker of a developmental cascade to future mental health problems for both mothers and offspring.