Postpartum depression: Etiology,treatment and consequences for maternal care

This article is part of a Special Issue “Parental Care”. Pregnancy and postpartum are associated with dramatic alterations in steroid and peptide hormones which alter the mothers' hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes. Dysregulations in these endocrine axes are related to mood disorders and as such it should not come as a major surprise that pregnancy and the postpartum period can have profound effects on maternal mood. Indeed, pregnancy and postpartum are associated with an increased risk for developing depressive symptoms in women. Postpartum depression affects approximately 10–15% of women and impairs mother–infant interactions that in turn are important for child development. Maternal attachment, sensitivity and parenting style are essential for a healthy maturation of an infant's social, cognitive and behavioral skills and depressed mothers often display less attachment, sensitivity and more harsh or disrupted parenting behaviors, which may contribute to reports of adverse child outcomes in children of depressed mothers. Here we review, in honor of the “father of motherhood”, Jay Rosenblatt, the literature on postnatal depression in the mother and its effect on mother–infant interactions. We will cover clinical and pre-clinical findings highlighting putative neurobiological mechanisms underlying postpartum depression and how they relate to maternal behaviors and infant outcome. We also review animal models that investigate the neurobiology of maternal mood and disrupted maternal care. In particular, we discuss the implications of endogenous and exogenous manipulations of glucocorticoids on maternal care and mood. Lastly we discuss interventions during gestation and postpartum that may improve maternal symptoms and behavior and thus may alter developmental outcome of the offspring.     

Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms

This article is part of a Special Issue “Parental Care”. Though hormonal changes occurring throughout pregnancy and at the time of parturition have been demonstrated to prime the maternal brain and trigger the onset of mother–infant interactions, extended experience with neonates can induce similar behavioral interactions. Sensitization, a phenomenon in which rodents engage in parental responses to young following constant cohabitation with donor pups, was elegantly demonstrated by Rosenblatt (1967) to occur in females and males, independent of hormonal status. Study of the non-hormonal basis of maternal behavior has contributed significantly to our understanding of hormonal influences on the maternal brain and the cellular and molecular mechanisms that mediate maternal behavior. Here, we highlight our current understanding regarding both hormone-induced and experience-induced maternal responsivity and the mechanisms that may serve as a common pathway through which increases in maternal behavior are achieved. In particular, we describe the epigenetic changes that contribute to chromatin remodeling and how these molecular mechanisms may influence the neural substrates of the maternal brain. We also consider how individual differences in these systems emerge during development in response to maternal care. This research has broad implications for our understanding of the parental brain and the role of experience in the induction of neurobiological and behavior changes.     

Chemical olfactory signals and parenthood in mammals

This article is part of a Special Issue “Chemosignals and Reproduction”.In mammalian species, odor cues emitted by the newborn are essential to establish maternal behavior at parturition and coordinate early mother–infant interactions. Offspring odors become potent attractive stimuli at parturition promoting the contact with the young to ensure that normal maternal care develops. In some species odors provide a basis for individual recognition of the offspring and highly specialized neural mechanisms for learning the infant signals have evolved. Both the main and the accessory olfactory systems are involved in the onset of maternal care, but only the former contributes to individual odor discrimination of the young. Electrophysiological and neurochemical changes occur in the main olfactory bulb leading to a coding of the olfactory signature of the familiar young. Olfactory neurogenesis could also contribute to motherhood and associated learning. Parturition and interactions with the young influence neurogenesis and some evidence indicates a functional link between olfactory neurogenesis and maternal behavior. Although a simple compound has been found which regulates anogenital licking in the rat, studies identifying the chemical nature of these odors are lacking. Neonatal body odors seem to be particularly salient to human mothers who are able to identify their infant's odors. Recent studies have revealed some neural processing of these cues confirming the importance of mother–young chemical communication in our own species.     

Neural mechanisms of mother–infant bonding and pair bonding: Similarities,differences, and broader implications

This article is part of a Special Issue “Parental Care”.Mother–infant bonding is a characteristic of virtually all mammals. The maternal neural system may have provided the scaffold upon which other types of social bonds in mammals have been built. For example, most mammals exhibit a polygamous mating system, but monogamy and pair bonding between mating partners occur in ~ 5% of mammalian species. In mammals, it is plausible that the neural mechanisms that promote mother–infant bonding have been modified by natural selection to establish the capacity to develop a selective bond with a mate during the evolution of monogamous mating strategies. Here we compare the details of the neural mechanisms that promote mother–infant bonding in rats and other mammals with those that underpin pair bond formation in the monogamous prairie vole. Although details remain to be resolved, remarkable similarities and a few differences between the mechanisms underlying these two types of bond formation are revealed. For example, amygdala and nucleus accumbens–ventral pallidum (NA–VP) circuits are involved in both types of bond formation, and dopamine and oxytocin actions within NA appear to promote the synaptic plasticity that allows either infant or mating partner stimuli to persistently activate NA–VP attraction circuits, leading to an enduring social attraction and bonding. Further, although the medial preoptic area is essential for maternal behavior, its role in pair bonding remains to be determined. Our review concludes by examining the broader implications of this comparative analysis, and evidence is provided that the maternal care system may have also provided the basic neural foundation for other types of strong social relationships, beyond pair bonding, in mammals, including humans.     

What is resilience: an affiliative neuroscience approach

Resilience – a key topic in clinical science and practice – still lacks a clear conceptualization that integrates its evolutionary and human‐specific features, refrains from exclusive focus on fear physiology, incorporates a developmental approach, and, most importantly, is not based on the negation (i.e., absence of symptoms following trauma). Building on the initial condition of mammals, whose brain matures in the context of the mother's body and caregiving behavior, we argue that systems and processes that participate in tuning the brain to the social ecology and adapting to its hardships mark the construct of resilience. These include the oxytocin system, the affiliative brain, and biobehavioral synchrony, all characterized by great flexibility across phylogenesis and ontogenesis. Three core features of resilience are outlined: plasticity, sociality and meaning. Mechanisms of sociality by which coordinated action supports diversity, endurance and adaptation are described across animal evolution. Humans' biobehavioral synchrony matures from maternal attuned behavior in the postpartum to adult‐adult relationships of empathy, perspective‐taking and intimacy, and extends from the mother‐child relationship to other affiliative bonds throughout life, charting a fundamental trajectory in the development of resilience. Findings from three high‐risk cohorts, each tapping a distinct disruption to maternal‐infant bonding (prematurity, maternal depression, and early life stress/trauma), and followed from birth to adolescence/young adulthood, demonstrate how components of the neurobiology of affiliation confer resilience and uniquely shape the social brain.     

Birth Timing and Behavioral Responsiveness Predict Individual Differences in the Mother–Infant Relationship and Infant Behavior During Weaning and Maternal Breeding

There is a great deal of variability in mother–infant interactions and infant behavior across the first year of life in rhesus monkeys. The current article has two specific aims: (1) to determine if birth timing predicts variability in the mother–infant relationship and infant behavior during weaning and maternal breeding, and (2) to identify predictors of infant behavior during a period of acute challenge, maternal breeding. Forty‐one mother–infant pairs were observed during weaning when infants were 4.5 months old, and 33 were followed through maternal breeding. Subjective ratings of 16 adjectives reflecting qualities of maternal attitude, mother–infant interactions, and infant attitude were factor analyzed to construct factors relating to the mother–infant relationship (Relaxed and Aggressive) and infant behavior (Positive Engagement and Distress). During weaning, late born infants were more Positively Engaged than peak born infants (ANOVA, P < 0.05); however, birth timing did not affect the mother–infant relationship factors Relaxed and Aggressive or the infant attitude factor Distress. During maternal breeding, early born infants had less Relaxed relationships with their mothers than peak or late born infants, higher Positive Engagement scores than peak or late born infants, and tended to have higher Distress scores than peak born infants (repeated‐measures ANOVA, P < 0.05). In addition, Distress scores were higher during maternal breeding than during the pre‐ and postbreeding phases. Finally, multiple regression (P < 0.05) indicated that while infant behavioral responsiveness predicted infant Positive Engagement during the acute challenge of maternal breeding, qualities of the mother–infant relationship predicted infant Distress. These data suggest that birth timing influences the patterns of mother–infant interactions during weaning and maternal breeding. Additionally, infant behavioral responsiveness and mother–infant relationship quality impact infant social engagement and affect expression, respectively. Am. J. Primatol. 74:734‐746, 2012. © 2012 Wiley Periodicals, Inc.     

Elevated corticosterone levels in stomach milk,serum, and brain of male and female offspring after maternal corticosterone treatment in the rat

Early influences such as maternal stress affect the developmental outcome of the offspring. We created an animal model of postpartum depression/stress based on giving high levels of corticosterone (CORT) to the rat dam, which resulted in behavioral and neural changes in the offspring. This study investigated whether highly elevated levels of maternal CORT during pregnancy or the postpartum result in higher levels of CORT in the stomach milk, serum, and brain of offspring. Dams received daily injections of CORT (40 mg/kg) or oil (control) either during pregnancy (gestational days 10–20) or the postpartum (Days 2–21). Pups that were exposed to high gestational maternal CORT had higher CORT levels in serum, but not in stomach milk or brain, on postnatal day (PND) 1. However, on PND7, pups that were exposed to high postpartum maternal CORT had higher CORT levels in stomach milk and brain, but not in serum. Conversely on PND18, pups that were exposed to high postpartum maternal CORT had higher CORT levels in serum, but not in brain (prefrontal cortex, hypothalamus, or hippocampus). Moreover, 24 h after weaning, there were no significant differences in serum CORT levels between the groups. Thus, CORT given to the dam during pregnancy or the postpartum results in elevated levels of CORT in the offspring, but in an age‐ and tissue‐dependent manner. Developmental exposure to high CORT could reprogram the HPA axis and contribute to the behavioral and neural changes seen in adult offspring. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 714–725, 2010     

Neuroplasticity in the maternal hippocampus: Relation to cognition and effects of repeated stress

This article is part of a Special Issue “Parental Care”. It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone–neuron interactions, all of which fundamentally change the neural architecture — and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model.     

Focus: Addiction: Investigating Maternal Brain Structure and its Relationship to Substance Use and Motivational Systems

Substance use during pregnancy and the postpartum period may have significant implications for both mother and the developing child. However, the neurobiological basis of the impact of substance use on parenting is less well understood. Here, we examined the impact of maternal substance use on cortical gray matter (GM) and white matter (WM) volumes and whether this was associated with individual differences in motivational systems of behavioral activation and inhibition. Mothers were included in the substance-using group if any addictive substance was used during pregnancy and/or in the immediate postpartum period (within 3 months of delivery). GM volume was reduced in substance-using mothers compared to non-substance-using mothers, particularly in frontal brain regions. In substance-using mothers, we also found that frontal GM was negatively correlated with levels of behavioral activation (i.e., the motivation to approach rewarding stimuli). This effect was absent in non-substance-using mothers. Taken together, these findings indicate a reduction in GM volume is associated with substance use and that frontal GM volumetric differences may be related to approach motivation in substance-using mothers.     

Neonatal hypernatremic dehydration associated with breast-feeding malnutrition: a retrospective survey

BACKGROUND: Hypernatremic dehydration in neonates is a potentially devastating condition. Recent reports have identified breast-feeding malnutrition as a key factor in its pathophysiology. METHODS: Using a theoretical framework for breast-feeding kinetics, a retrospective chart review of all neonates less than 28 days of age who were seen at either British Columbia''s Children''s Hospital or the Vancouver Breastfeeding Centre between 1991-1994 was conducted to identify and classify possible causes of breast-feeding malnutrition among neonates who developed hypernatremic dehydration. RESULTS: Twenty-one cases hypernatremic dehydration were identified. Infant weight loss ranged from 8% to 30% of birth weight, and serum sodium levels ranged from 146 mmol/L to 207 mmol/L. In each case, maternal or infant factors (e.g., poor breast-feeding technique, lactation failure following postpartum hemorrhage and infant suckling disorders associated with cleft palate or ankyloglossia) that could interfere with either lactation or breast-feeding dynamics and account for insufficient breast milk intake were identified. INTERPRETATION: Prenatal and in-hospital screening for maternal and infant risk factors for breast-feeding malnutrition combined with early postpartum follow-up to detect excessive infant weight loss are important for the prevention of neonatal hypernatremic dehydration.     

Physiological mechanisms,behavioral and psychological factors influencing the transfer of milk from mothers to their young

This article is part of a Special Issue “Parental Care”.Producing milk to support the growth of their young is a central element of maternal care in mammals. In spite of the facts that ecological constraints influence nursing frequency, length of time until weaning and the composition of milk, there is considerable similarity in the anatomy and physiology of milk production and delivery across mammalian species. Here we provide an overview of cross species variation in nursing patterns and milk composition as well as the mechanisms underlying mammary gland development, milk production and letdown. Not all women breastfeed their infants, thus in later sections we review studies of factors that facilitate or impede the initiation and duration of breastfeeding. The results of these investigations suggest that the decisions to initiate and maintain breastfeeding are influenced by an array of personal, social and biological factors. Finally, studies comparing the development of breastfed and formula fed infants as well as those investigating associations between breastfeeding, maternal health and mother/infant interaction are reviewed. Leading health agencies including the World Health Organization and CDC advocate breastfeeding for at least the first 6 months postpartum. To achieve these rates will require not only institutional support but also a focus on individual mother/infant dyads and their experience.     

Neuroanatomical and neurochemical basis of parenting: Dynamic coordination of motivational,affective and cognitive processes

This article is part of a Special Issue “Parental Care”. Becoming a parent is arguably the most profound transforming experience in life. It is also inherently very emotionally and physically demanding, such that the reciprocal interaction with the young changes the brain and behavior of the parents. In this review, we examine the neurobiological mechanisms of parenting primarily discussing recent research findings in rodents and primates, especially humans. We argue that it is essential to consider parenting within a conceptual framework that recognizes the dynamics of the reciprocal mother–young relationship, including both the complexity and neuroplasticity of its underlying mechanisms. Converging research suggests that the concerted activity of a distributed network of subcortical and cortical brain structures regulates different key aspects of parenting, including the sensory analysis of infant stimuli as well as motivational, affective and cognitive processes. The interplay among these processes depends on the action of various neurotransmitters and hormones that modulate the timely and coordinated execution of caregiving responses of the maternal circuitry exquisitely attuned to the young's affect, needs and developmental stage. We conclude with a summary and a set of questions that may guide future research.     

Reported maternal tendencies predict the reward value of infant facial cuteness,but not cuteness detection

The factors that contribute to individual differences in the reward value of cute infant facial characteristics are poorly understood. Here we show that the effect of cuteness on a behavioural measure of the reward value of infant faces is greater among women reporting strong maternal tendencies. By contrast, maternal tendencies did not predict women''s subjective ratings of the cuteness of these infant faces. These results show, for the first time, that the reward value of infant facial cuteness is greater among women who report being more interested in interacting with infants, implicating maternal tendencies in individual differences in the reward value of infant cuteness. Moreover, our results indicate that the relationship between maternal tendencies and the reward value of infant facial cuteness is not due to individual differences in women''s ability to detect infant cuteness. This latter result suggests that individual differences in the reward value of infant cuteness are not simply a by-product of low-cost, functionless biases in the visual system.     

Interaction between Oxytocin Genotypes and Early Experience Predicts Quality of Mothering and Postpartum Mood

Individual differences in maternal behavior are affected by both early life experiences and oxytocin, but little is known about genetic variation in oxytocin genes and its effects on mothering. We examined two polymorphisms in the oxytocin peptide gene OXT (rs2740210 and rs4813627) and one polymorphism in the oxytocin receptor gene OXTR (rs237885) in 187 Caucasian mothers at six months postpartum. For OXT, both rs2740210 and rs4813627 significantly associated with maternal vocalizing to the infant. These polymorphisms also interacted with the quality of care mothers experienced in early life, to predict variation in maternal instrumental care and postpartum depression. However, postpartum depression did not mediate the gene-environment effects of the OXT SNPs on instrumental care. In contrast, the OXTR SNP rs237885 did not associate with maternal behavior, but it did associate with pre-natal (but not post-natal) depression score. The findings illustrate the importance of variation in oxytocin genes, both alone and in interaction with early environment, as predictors of individual differences in human mothering. Furthermore, depression does not appear to have a causal role on the variation we report in instrumental care. This suggests that variation in instrumental care varies in association with a gene-early environment effect regardless of current depressive symptomatology. Finally, our findings highlight the importance of examining multiple dimensions of human maternal behavior in studies of genetic associations.     

What causes intraspecific variation in resting metabolic rate and what are its ecological consequences?

Individual differences in the energy cost of self-maintenance (resting metabolic rate, RMR) are substantial and the focus of an emerging research area. These differences may influence fitness because self-maintenance is considered as a life-history component along with growth and reproduction. In this review, we ask why do some individuals have two to three times the ‘maintenance costs’ of conspecifics, and what are the fitness consequences? Using evidence from a range of species, we demonstrate that diverse factors, such as genotypes, maternal effects, early developmental conditions and personality differences contribute to variation in individual RMR. We review evidence that RMR is linked with fitness, showing correlations with traits such as growth and survival. However, these relationships are modulated by environmental conditions (e.g. food supply), suggesting that the fitness consequences of a given RMR may be context-dependent. Then, using empirical examples, we discuss broad-scale reasons why variation in RMR might persist in natural populations, including the role of both spatial and temporal variation in selection pressures and trans-generational effects. To conclude, we discuss experimental approaches that will enable more rigorous examination of the causes and consequences of individual variation in this key physiological trait.     

Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

Life‐history theory predicts that access to limited resources leads to trade‐offs between competing body functions. Women, who face higher costs of reproduction when compared to men, should be especially vulnerable to these trade‐offs. We propose the ‘cognitive costs of reproduction hypothesis’, which states that energy trade‐offs imposed by reproduction may lead to a decline in maternal cognitive function during gestation. In particular, we hypothesize that the decline in cognitive function frequently observed during pregnancy is associated with the allocation of resources between the competing energetic requirements of the mother's brain and the developing foetus. Several distinctive anatomical and physiological features including a high metabolic rate of the brain, large infant size, specific anatomical features of the placenta and trophoblast, and the lack of maternal control over glucose flow through the placenta make the occurrence of these trade‐offs likely. Herein, we review several lines of evidence for trade‐offs between gestation and cognition that are related to: (i) energy metabolism during reproduction; (ii) energy metabolism of the human brain; (iii) links between energy metabolism and cognitive function; and (iv) links between gestation and cognitive function. We also review evidence for the important roles of cortisol, corticotropin‐releasing hormone and sex hormones in mediating the effects of gestation on cognition, and we discuss possible neurophysiological mechanisms underlying the observed effects. The evidence supports the view that energy trade‐offs between foetal growth and maternal endocrine and brain function lead to changes in maternal cognition, and that this phenomenon is mediated by neuroendocrine mechanisms involving the hypothalamic–pituitary–adrenal axis, brainstem nucleus locus coeruleus and hippocampus.     

The emergence and maintenance of interdyad differences in the mother-infant relationships of rhesus macaques: A correlational study

The role of the mother in promoting infant independence, reflected in the time spent out of contact with her by the infant, was addressed with a simple correlational approach to scores of time out of contact (Off) and frequencies of acts of maternal rejection and restriction through the infants’ first 16 weeks of life. Correlations of the extents of age changes from week to week were also examined. Infants differed consistently in the times they spent off from their fourth through their eighth weeks, while rates of maternal restriction and rejection were consistent from week 4 until at least week 8 in both sexes and from week 2 in females. The correlations were consistent with the view that time off was set at its week-4 and possibly later levels by maternal rejection, while some further changes in time off, resulting in a loss of consistency from week to week, reflected the extents to which mothers of daughters decreased their restrictive behavior. Weeks in which individual differences in maternal restriction and rejection were correlated with differences in time spent off were generally weeks in which changes in group means of these mean measures were correlated. In daughters, age changes of individual dyad’s scores of time off and maternal rejection were correlated between week 2 and week 4, supporting the view that in these early weeks age changes and individual differences were produced by the same processes. Findings from comparative and experimental studies, and the limitations of correlational approaches now available, are discussed.     

Associations among within-litter differences in early mothering received and later emotional behaviors,mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats

This article is part of a Special Issue “Parental Care”. The effects of differential maternal care received on offspring phenotype in rodents has been extensively studied between litters, but the consequences of differential mothering within litters on offspring neurobehavioral development have been rarely examined. We here investigated how variability in maternal care received among female rat siblings (measured four times daily on postnatal days 4, 6, 8, and 10) relates to the siblings' later emotional and maternal behaviors. As previously reported, we found that some female pups received up to three times more maternal licking bouts compared to their sisters; this difference was positively correlated with the pups' body weights. The number of maternal licking bouts that females received was negatively correlated with their later neophobic behaviors in an open field during periadolescence, but positively correlated with their anxiety-related behavior in an elevated plus maze during adulthood. Licking received was also positively correlated with females' later likelihood to retrieve pups in a maternal sensitization paradigm. In addition, females' neophobia during adolescence and anxiety-related behavior during adulthood predicted some aspects of both postpartum and sensitized maternal responsiveness. Medial prefrontal cortex expression of tryptophan hydroxylase-2 (TPH2; enzyme necessary for serotonin synthesis) was negatively associated with early maternal licking received. Interestingly, cortical TPH2 was positively associated with the maternal responsiveness of sensitized virgins but negatively associated with it in postpartum females. These results indicate that within-litter differences in maternal care received is an often neglected, but important, contributor to individual differences in offspring socioemotional behaviors as well as to the cortical serotonin neurochemistry that may influence these behaviors.     

Exploring the neural basis of cognitive reserve in aging

The concept of reserve arose from the mismatch between the extent of brain changes or pathology and the clinical manifestations of these brain changes. The cognitive reserve hypothesis posits that individual differences in the flexibility and adaptability of brain networks underlying cognitive function may allow some people to cope better with brain changes than others. Although there is ample epidemiologic evidence for cognitive reserve, the neural substrate of reserve is still a topic of ongoing research. Here we review some representative studies from our group that exemplify possibilities for the neural substrate of reserve including neural reserve, neural compensation, and generalized cognitive reserve networks. We also present a schematic overview of our ongoing research in this area. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.