Rixt van der Veen

Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration.

We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 a.m.) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7 h in total. Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1 h after administration, and were still significantly elevated 7 h after administration. The amount of oxytocin (16 or 24 IU) did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7 h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

Development of individual differences in stress responsiveness: an overview of factors mediating the outcome of early life experiences

RationaleHuman epidemiology and animal studies have convincingly shown the long-lasting impact of early life experiences on the development of individual differences in stress responsiveness in later life. The interplay between genes and environment underlies this phenomenon.ObjectivesWe provide an overview of studies investigating the impact of early life experiences on the development of individual differences in neuroendocrine stress responsiveness in adulthood and address (1) impact of environment on later stress phenotypes, (2) role of genetic factors in modulating the outcome of environment, and (3) role of nonshared environmental experience in the outcome of gene × environment interplays. We present original findings where we investigated the influence of nonshared experiences in terms of individual differences in maternal care received, on the development of stress phenotype in later life in rats.ResultsEnvironmental influences in early life exert powerful effects on later stress phenotypes, but they do not always lead to expression of diseases. Heterogeneity in response is explained by the role of particular genetic factors in modulating the influence of environment. Nonshared experiences are important in the outcome of gene × environment interplays in humans. We show that nonshared experiences acquired through within-litter variation in maternal care in rats predict the stress phenotype of the offspring.ConclusionThe outcome of early experience is not deterministic and depends on several environmental and genetic factors interacting in an intricate manner to support stress adaptation. The degree of “match” and “mismatch” between early and later life environments predicts resilience and vulnerability to stress-related diseases, respectively.

One doll fits all: validation of the Leiden Infant Simulator Sensitivity Assessment (LISSA)

Children vary hugely in how demanding of their caregivers they are. This creates differences in demands on parents during observation, making the comparison of sensitivity between parents difficult. It would therefore be of interest to create standard situations in which all caregivers are faced with the same level of demand. This study developed an ecologically valid but standardized setting using an infant simulator with interactive features, the Leiden Infant Simulator Sensitivity Assessment (LISSA). The infant simulator resembles a real infant in appearance and it produces crying sounds that are life-like. The simulator begins with fussing and progresses to more intense crying in case of no care or inappropriate care. It responds by being calm again if appropriate care is given. One hundred and eighty-one female participants took care of the infant simulator for two evenings and in a 30 min lab session with increasing competing demands. Sensitive parenting behavior during the lab session was coded with the Ainsworth Sensitivity Scale. Sensitivity ratings covered the whole range of the scale (1–9), and were stable across settings (free play, competing demands). Sensitivity was related to an increase of positive affect during caretaking, and insensitivity was related to intended harsh caregiving response during a computerized cry paradigm. Sensitivity was unrelated to social desirability and self-reported quality of care given to the infant simulator. We discuss the potentials of the infant simulator for research on sensitive parenting, for preventive interventions, and for clinical practices.

Interplay of Maternal Care and Genetic Influences in Programming Adult Hippocampal Neurogenesis

BACKGROUND Adult hippocampal neurogenesis, which is involved in the physiopathology of hippocampal functions, is genetically determined and influenced by early life events. However, studies on the interaction of these determining forces are lacking. This prompted us to investigate whether adult hippocampal neurogenesis can be modulated by maternal care and whether this influence depends upon the genetic background of the individual. METHODS We used a model of fostering that allows singling out the influence of the genetic make-up of the pups on the outcome of maternal behavior. Mice from two different inbred strains (C57BL/6J and DBA/2J) known to differ in their baseline neurogenesis as well as in their sensitivity to the influence of environmental experiences were raised by nonrelated mothers from the AKR/Ola (AKR) and C3H/He (C3H) strains exhibiting low- and high-pup-oriented behavior, respectively. Neurogenesis was then assessed in the dentate gyrus of the adult adopted C57BL/6J and DBA/2J mice. RESULTS We show that both the number and the morphological features of newborn granule cells in the dentate gyrus are determined by the maternal environment to which mice were exposed as pups and that this sensitivity to maternal environment is observed only in genetically vulnerable subjects. CONCLUSIONS Altogether, our data indicate interplay between early environment and the genetic envelop of an individual in determining adult hippocampal neurogenesis. Our experimental approach could thus contribute to the identification of factors determining the neurogenic potential of the adult hippocampus.

Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice

Social interaction with unknown individuals requires fast processing of information to decide whether it is friend or foe. This process of discrimination and decision-making is stressful and triggers secretion of corticosterone activating mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The MR is involved in appraisal of novel experiences and risk assessment. Recently, we have demonstrated in a dual-solution memory task that MR plays a role in the early stage of information processing and decision-making. Here we examined social approach and social discrimination in male and female mice lacking MR from hippocampal-amygdala-prefrontal circuitry and controls. The social approach task allows the assessment of time spent with an unfamiliar mouse and the ability to discriminate between familiar and unfamiliar conspecifics. The male and female test mice were both more interested in the social than the non-social experience and deletion of their limbic MR increased the time spent with an unfamiliar mouse. Unlike controls, the male MRCaMKCre mice were not able to discriminate between an unfamiliar and the familiar mouse. However, the female MR mutant had retained the discriminative ability between unfamiliar and familiar mice. Administration of the MR antagonist RU28318 to male mice supported the role of the MR in the discrimination between an unfamiliar mouse and a non-social stimulus. No effect was found with a GR antagonist. Our findings suggest that MR is involved in sociability and social discrimination in a sex-specific manner through inhibitory control exerted putatively via limbic-hippocampal efferents. The ability to discriminate between familiar and unfamiliar conspecifics is of uttermost importance for territorial defense and depends on a role of MR in decision-making.

Temperamental sensitivity moderates the effects of maternal love-withdrawal on perception of infant crying

Parenting has an impact on the offsprings social and behavioral outcomes. However, not all individuals are affected equally; according to the differential susceptibility hypothesis, temperamental traits may moderate the effects of early life experiences. We examined the association between young adults’ experiences of maternal love-withdrawal and their perception of infant crying, and the potentially moderating role of temperamental orienting sensitivity. In an ecologically valid but standardized setting, 132 female participants spent two consecutive evenings taking care of an infant simulator. Orienting sensitivity moderated the relation between experienced love-withdrawal and the perception of infant crying: Participants with high orienting sensitivity who experienced low levels of love-withdrawal perceived the crying bouts as less negative than others. We conclude that the long-term impact of early life experiences may be moderated by temperamental characteristics, with implications for individual differences in perceptual responses to infant stimuli in adulthood.

The added value of rodent models in studying parental influence on offspring development: opportunities, limitations and future perspectives

Over the past decades, the influence of parental care on offspring development has been a topic of extensive research in both human and animal models. Rodent models offer several unique advantages over human studies, allowing for higher levels of environmental control, exploration of interventions, genetic control and examination of underlying neurobiological mechanisms in greater spatiotemporal detail. Although exploitation of these opportunities has led to increased understanding of the neurobiological mechanisms underlying susceptibility to the early-life environment, translation of results to human parenting and child development appears to be challenging. Attuning animal models to the human situation and application of novel structural and functional techniques is therefore of crucial importance to reduce the gap between rodent and human research.

Mifepristone Treatment during Early Adolescence Fails to Restore Maternal Deprivation-Induced Deficits in Behavioral Inhibition of Adult Male Rats.

Early life adversity has a profound impact on brain development and later life health. Animal models have provided insight how early life stress programs stress responsiveness and might contribute to the development of psychiatric disorders. In the present study, the long-term effects of maternal deprivation (MD) on behavioral inhibition and attention were examined in adult male Wistar rats. To this end animals were tested in the 5-choice serial reaction time task (5-choice SRTT). We also explored the potential of a 3-day treatment with the glucocorticoid receptor (GR) antagonist mifepristone during early adolescence to normalize putative behavioral effects of early life stress. Deprivation of the mother for 24 h on postnatal day (PND) 3 led to a modest but significant increase in premature responses in the 5-choice SRTT, but did not affect measures of attention. Body weight was lower in deprived animals from weaning until the start of testing. Early adolescent mifepristone treatment (PND 26–28) did not influence performance on the 5-choice SRTT and did not mitigate the deprivation-related impairment in behavioral inhibition. Our results indicate that MD leads to impaired behavioral inhibition, and that mifepristone treatment during early adolescence does not normalize the behavioral changes caused by early life stress.

Complex Living Conditions Impair Behavioral Inhibition but Improve Attention in Rats

Rapid adaptation to changes, while maintaining a certain level of behavioral inhibition is an important feature in every day functioning. How environmental context and challenges in life can impact on the development of this quality is still unknown. In the present study, we examined the effect of a complex rearing environment during adolescence on attention and behavioral inhibition in adult male rats. We also tested whether these effects were affected by an adverse early life challenge, maternal deprivation (MD). We found that animals that were raised in large, two floor MarlauTM cages, together with 10 conspecifics, showed improved attention, but impaired behavioral inhibition in the 5-choice serial reaction time task. The early life challenge of 24 h MD on postnatal day 3 led to a decline in bodyweight during adolescence, but did not by itself influence responses in the 5-choice task in adulthood, nor did it moderate the effects of complex housing. Our data suggest that a complex rearing environment leads to a faster adaptation to changes in the environment, but at the cost of lower behavioral inhibition.

Childhood Maltreatment Experiences and Child Abuse Potential: Temperamental Sensitivity as Moderator?

This study aimed to examine the relationship between negative experiences in childhood (physical-, sexual-, and emotional abuse and emotional neglect) and the risk for an individual to become a perpetrator of child maltreatment in adulthood. Participants were 337 female college students who completed self-report measures of childhood trauma and temperament. Risk for child abuse was assessed with the Child Abuse Potential Inventory. Results showed experiences of emotional neglect significantly predicted higher child abuse potential. Additionally it was shown that experiences of physical abuse significantly predicted higher child abuse potential but only in those individuals with high temperamental orienting sensitivity. These results underline the potentially damaging long-term effects of emotional neglect in childhood and indicate temperamental sensitivity may moderate the relationship between being abused as a child and being at risk for maltreating one’s own offspring.