High Maternal Care Research Articles

Influences of quality of maternal care and environmental enrichment on associative memory function in rats with early life lead exposure.

Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure. Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From postnatal days (PNDs) 2-9, maternal care behaviors were observed, and dams were classified as low or high maternal care based on amounts of licking/grooming and arched back nursing. At weaning, pups were randomly assigned to enriched or non-enriched environments. At PND 55, animals began trace fear conditioning and associative memory was tested on days 1, 2, and 10 postconditioning. Control offspring showed no significant effects of maternal care or enrichment on task performance. Females with EPN-Pb exposure and males with PERI-Pb exposure living in the non-enriched environment and having an LMC mother had significant memory impairments at days 2 and 10 that were not observed in comparably housed animals with HMC mothers. Enriched animals had no deficits, regardless of maternal care status. These results show the potential for modulatory influences of maternal care and housing environment on protecting against or reversing at least one aspect of Pb-induced cognitive/behavioral dysfunction.

The effect of cognitive reappraisal and early-life maternal care on neuroendocrine stress responses

Early-life adversity (ELA) is related to profound dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, reflected in both, blunted or exaggerated cortisol stress responses in adulthood. Emotion regulation strategies such as cognitive reappraisal might contribute to this inconsistent finding. Here, we investigate an interaction of early-life maternal care (MC), where low MC represents a form of ELA, and instructed emotion regulation on cortisol responses to acute stress. Ninety-three healthy young women were assigned to a low (n = 33) or high (n = 60) MC group, based on self-reported early-life MC. In the laboratory, participants received regulation instructions, asking to cognitively reappraise (reappraisal group, n = 45) or to focus on senses (control group, n = 48) during subsequent stress exposure, induced by the Trier Social Stress Test. Salivary cortisol and subjective stress levels were measured repeatedly throughout the experiment. Multilevel model analyses confirmed a MC by emotion regulation interaction effect on cortisol trajectories, while controlling for hormonal status. Individuals with low MC in the control compared with the reappraisal group showed increased cortisol responses; individuals with high MC did not differ. These results highlight the significance of emotion regulation for HPA axis stress regulation following ELA exposure. They provide methodological and health implications, indicating emotion regulation as a promising target of treatment interventions for individuals with a history of ELA.

Patterns of resilient functioning in early life: Identifying distinct groups and associated factors.

Resilience, the capacity to maintain or regain functionality in the face of adversity, is a dynamic process influenced by individual, familial, and community factors. Despite its variability, distinct resilience trajectories can be identified within populations, yet the predictors defining these distinct groups remains largely unclear. Here, using data from the Avon Longitudinal Study of Parents and Children (ages 0-18), we quantify resilience as the remaining variance in psychosocial functioning after taking into account the exposure to adversity. Growth mixture modeling identified seven distinct resilience trajectories, with over half of the study population maintaining resilience throughout early life. Factors increasing the likelihood of resilient trajectory membership included a less emotional temperament, high cognitive abilities, high self-esteem, low levels of autistic social traits, strong sibling relationships, high maternal care, and positive school experiences. Among the socioeconomic factors considered, maternal education - a significant indicator of socioeconomic status - and birth-order were associated with resilient trajectories. Our findings underscore the importance of fostering cognitive abilities, self-esteem, social relationships, positive school experiences, and extracurricular engagement to bolster resilience in adversity-exposed individuals and communities. This research informs resilience-focused interventions in mental health, education, and social policy sectors, and prompts further exploration of socioeconomic influences on resilience trajectories.

Individual and context correlates of the oral pill and condom use among Brazilian female adolescents

BackgroundStudies have examined the impact of contextual factors on the use of contraceptives among adolescents and found that many measures of income and social inequality are associated with contraceptive use. However, few have focused on maternal and primary health indicators and its influence on adolescent contraceptive use. This paper assesses whether maternal mortality rates, antenatal care visits, and primary healthcare coverage are associated with pill and condom use among female adolescents in Brazil.MethodsWe used data from the Study of Cardiovascular Risks in Adolescents (ERICA), a national, school-based cross-sectional study conducted in Brazil. A subsample of all female adolescents who had ever had sexual intercourse and were living in one of the 26 State capitals and the Federal District was selected (n = 7415). Multilevel mixed effects logistic regression models were estimated to examine the effect of contextual variables on pill and condom use.ResultsSixty-five percent of female adolescents reported using pill while 21.9% reported using condom during the last sexual intercourse. Adolescents living in municipalities with low maternal mortality and high antenatal care coverage were significantly more likely to use pill during the last sexual intercourse compared to those from municipalities with high maternal mortality and low antenatal care coverage. Primary healthcare coverage (proportion of the population covered by primary healthcare teams) was not significantly associated with either condom or pill use during the last sexual intercourse.ConclusionOur findings suggest that promoting the use of pill among female adolescents may require approaches to strengthen healthcare systems rather than those focused solely on individual attributes.

Perceived parental bonding and cortisol awakening response in people with eating disorders

It is widely acknowledged that early life experiences may have an impact on hypothalamic–pituitary–adrenal (HPA) axis functioning in eating disorders (EDs). Parental bonding is defined as the parental contribution of care and control to parent–child relationships. We evaluated whether perceived care and protection of parental bonding in childhood and adolescence were associated with HPA axis functioning in adult patients with EDs.Sixty-four women with EDs participated in the study, 37 with anorexia nervosa and 27 with bulimia nervosa. Parental care and control (separately for the mother and father) were evaluated by the Parental Bonding Instrument. The activity of the HPA axis was assessed by measuring the salivary cortisol awakening response (CAR).Parental care and control did not differ significantly between the two diagnostic groups. High and low maternal care were associated with significantly different time patterns of CAR without any significant difference in the overall post-awakening production of cortisol. Maternal control, paternal care and paternal control were not associated with any difference in the CAR.Our results showed for the first time an association of perceived maternal care with the time pattern of CAR in female patients with EDs, while perceived parental control was not associated with any CAR feature. These findings support the idea that perceived characteristics of parental bonding in childhood and adolescence may influence the HPA axis activity in adults with EDs.

Quality of early-life maternal care predicts empathy-like behavior in adult male rats: Linking empathy to BDNF gene expression in associated brain regions

Empathy is the ability to experience a shared affective state as others. It enhances group living and manifests itself as helping behavior towards a distressed person. It also can flourish by nurturing. Recent findings suggest that rodents exhibit empathy-like behavior towards their conspecifics. However, the role of early-life experiences (e.g., maternal care) is not clear on the development of empathy-like behavior. Moreover, brain-derived neutrophilic factor (BDNF) is a pivotal protein in modulating the brain's function and behaviors. Evidence suggests that the expression of the BDNF gene can be affected by the quality of maternal care. In this study, we questioned whether variation in maternal care modulates empathy-like behavior of male rats in adulthood. Additionally, gene expression of BDNF was measured in the amygdala, hippocampus, insula, anterior cingulate cortex, prefrontal cortex, and striatum in these adult male rats. Based on the pattern of maternal care, the offspring were divided into high maternal care (HMC) and low maternal care (LMC) groups. We confirmed that the early-life experience of HMC significantly promoted the empathy-like behavior of rats in adulthood compared to LMC. In terms of gene expression, the HMC group consistently had higher BDNF gene expression in all studied regions, except anterior cingulate cortex which groups were not different. Taken together, it suggests that maternal care in infancy predicts empathy-like behavior in adulthood and differences in BDNF gene expression in different brain regions may reflect the underlying mechanism.

The impact of maternal care and blood glucose availability on the cortisol stress response in fasted women

Individuals with a history of low maternal care (MC) frequently present a blunted, yet sometimes also show an increased cortisol stress response. Fasted individuals with low blood glucose levels who are exposed to acute stress typically show an attenuated response pattern in this endocrine marker. Despite well-documented metabolic dysregulations after low MC, a possible interaction of both factors has not been investigated yet. Here, we examined the effects of MC and blood glucose concentration on various aspects of the stress response. Fasted women (N = 122, meanage = 22.12, sdage = 2.56) who experienced either very high, high, or low MC (based on the Parental Bonding Instrument) were randomly assigned to consume grape juice (condition sugar), or water (condition water) prior to being exposed to the Trier-Social-Stress-Test for groups. Salivary cortisol and alpha amylase, blood glucose, and mood ratings were assessed repeatedly. Using multilevel mixed models, we replicated the boosting effect of glucose on the cortisol stress response. While we found neither an effect of MC, nor an interaction between MC and blood glucose availability on the cortisol stress response, we observed an effect of MC on the amylase stress response. We discuss the results in the light of links between various stress/energy systems that possibly mediate health-related MC effects.

Interaction between childhood parental bonding and affective temperaments on adulthood depressive symptoms

• Interaction between parental bonding and affective temperaments was studied. • Hyperthymic temperament decreases depressogenic effect of paternal overprotection. • Maternal care reduces depressogenic effect of temperament excluding hyperthymic one. • Evaluating such interactions may be useful in dealing with depressive symptoms. Childhood parental bonding and affective temperaments influence adulthood mood symptoms, and childhood maltreatment has an effect on the affective temperaments present in adulthood depressive symptoms. However, whether childhood parental bonding interacts with affective temperaments related to adulthood depressive symptoms has not been investigated. Therefore, this study aimed to study the interaction between childhood parental bonding and these effects in community adults. The 548 adult community volunteers were assessed using the Parental Bonding Instrument, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire version, and Patient Health Questionnaire-9. The interactions were evaluated using hierarchical multiple regression analysis. High paternal care significantly and positively interacted with anxious temperament in depressive symptoms, whereas high paternal overprotection significantly and negatively interacted with hyperthymic temperament in depressive symptoms. High maternal care significantly and negatively interacted with cyclothymic, depressive, irritable, and anxious temperaments in depressive symptoms. High maternal overprotection had no significant interaction with any affective temperament in depressive symptoms. All participants were community volunteers, which prevents generalization to other community individuals. The cross-sectional design prevents explanation of the causal links in the study parameters. This study suggests that childhood parental bonding interacts with affective temperaments in adulthood depressive symptoms. High maternal care decreases the depressogenic effects of cyclothymic, depressive, irritable, and anxious temperaments, although maternal care may not interact with hyperthymic temperament. The moderator effects of maternal care may be involved in the differences between the effects of hyperthymic temperament and other temperaments on adulthood depressive symptoms.

Early Life Maternal Separation and Maternal Behaviour Modulate Acoustic Characteristics of Rat Pup Ultrasonic Vocalizations

Early separation of preterm infants from their mothers has adverse, long-term neurodevelopmental consequences. We investigated the effects of daily maternal separation (MS) of rat pups from postnatal days 2–10 (PND2–10) on neurobehavioural responses to brief isolation at PND12 compared with pups receiving controlled handling without MS. Ultrasonic vocalizations (USV) were measured at PND12 during two, 3-minute isolations occurring immediately before and after a 3-minute maternal reunion. There were no significant differences in acoustic characteristics between MS and control animals in the first isolation. However, in the second isolation, MS pups produced a greater proportion of high (~60 kHz) vs low (~40 kHz) frequency calls. During this isolation, control pups made longer and louder low frequency calls compared to the first isolation, whereas MS pups did the opposite. Maternal behaviour of control and MS mothers modulated pup acoustic characteristics in opposite directions; higher maternal care was associated with more low frequency calls in control pups but more high frequency calls in MS pups. We hypothesize that MS results in USV emission patterns reflective of a greater stress response to isolation. This translational model can be used to identify mechanisms and interventions that may be exploited to overcome the negative, long-term effects of MS.

Higher maternal care and tolerance in more experienced giraffe mothers

Maternal investment and maternal care provided by mammalian females can change during their ontogeny. Differences may be related to the age and/or experience (parity) of the female. Several hypotheses have been postulated to explain changes in the rate of maternal care of females during their lifetime. The residual reproductive value hypothesis supposes a higher rate of maternal care in older and more experienced females, in contrast the targeted reproductive effort hypothesis predicts lower levels of maternal care in older and/or more experienced females. To test these hypotheses we investigated nursing bout frequency and time devoted to nursing as predictors of the rate of maternal care, and rate of successful nursing bouts as a predictor of maternal investment, in captive giraffe (22 females, 47 calves in four zoos). We also considered the high rate of allonursing (nursing of non-filial calves) which appeared in all herds. The nursing and allonursing bout frequency as well as the total time devoted to nursing and allonursing increased with increasing parity and age of the female, thus supporting the residual reproductive value hypothesis. In addition, maternal experience of individual females in terms of parity rather than age was responsible for variation in maternal behaviour. This suggests that variation depends on individual experiences.

Link of negative core beliefs about the self with perceived dysfunctional parenting

Cognitive theory posits the central role of negative core beliefs about the self in cognitive vulnerabilities to depression, and this position is supported by empirical studies. It is also hypothesized that these core beliefs develop as a result of negative interactions with significant others in early life. To test the hypothesis that negative core beliefs about the self are formed by dysfunctional parenting, we examined their relations with perceived parental rearing. The subjects were 355 Japanese healthy volunteers. Core beliefs of negative-self were assessed by the corresponding subscale of the Brief Core Schema Scales. Perceived parental care and protection were evaluated by the corresponding subscales of the Parental Bonding Instrument. In both multiple regression analysis and structural equation modeling, core beliefs of negative-self were predicted by perceptions of high maternal protection and low paternal care. The present study shows that negative core beliefs about the self are linked with perceived dysfunctional parenting, suggesting that the formation mechanism of these core beliefs is at least partly ascribable to dysfunctional parenting.

Parenting style and mental disorders in a nationally representative sample of US adolescents

We examined associations between parenting style and past-year mental disorders in a nationally representative cross-sectional survey of US adolescents and whether the associations differed by adolescent demographic characteristics. The sample included 6483 adolescents aged 13-18years who were interviewed for a full range of DSM-IV mental disorders. Parenting style was assessed by adolescent-reported maternal and paternal care and control using items from the Parental Bonding Instrument. We controlled for socio-demographics, parental history of mental disorders, stressful life events, sexual violence, inter-parental conflict, and household composition. We also tested for two-way interactions between parental care and control and adolescent age, sex, and race/ethnicity. In adjusted models, high maternal care was associated with lower odds of depressive, eating, and behavioral disorders, and high maternal control was associated with greater odds of depressive, anxiety, eating, and behavioral disorders. High paternal care was associated with lower odds of social phobia and alcohol abuse/dependence. High paternal control was associated with greater odds of agoraphobia and alcohol abuse/dependence but with lower odds of attention-deficit/hyperactivity disorder. Associations of maternal and paternal control with anxiety disorders and substance abuse/dependence differed by sex. High paternal care was associated with lower odds of anxiety disorders only among Hispanics and non-Hispanic blacks. Perceived parental care and control were associated with adolescent mental disorders after controlling for multiple potential confounders. Differential patterns of association were found according to adolescent sex and race/ethnicity. Findings have implications for prevention and intervention programs that incorporate familial contextual factors.

Parental Bonding in Adolescents With and Without Chronic Pain.

Parental responses influence children's pain; however, the specific role of parental bonding in pediatric pain has not been examined. Depressive symptomology is frequently reported in children with chronic pain (CP) and may play a role in the relationship between parental bonding and pain. This study examined the connections between maternal/paternal bonding (perceived care and control) and symptoms of pain and depression in adolescents with CP and in healthy adolescents. Participants included 116 adolescents (aged 12-17) with CP (n = 55) and without (n = 61). Adolescents completed the Parental Bonding Instrument separately for their mother and father, as well as measures of depression and pain. Significant associations between parental bonding and adolescent pain and depression emerged in the pain group, but not in the healthy group. There were no differences in the impact of maternal versus paternal bonding on adolescent pain and depression. Mediation analyses revealed adolescent depression was a mediator of the relationship between maternal care and adolescent pain, and paternal control and adolescent pain in the group with CP. This study highlights the importance of considering parental bonding and adolescent depression in pediatric CP, suggesting that high paternal control and low maternal care contribute to increased pain in adolescents through heightened adolescent depressive symptoms. The findings emphasize the need for family-based treatment for CP that addresses parent behaviors and adolescent mental health.

Lasting effects of early life stress in mice: interaction of maternal environment and infant genes.

In the mouse, a powerful paradigm of early life stress, infant maternal separation (IMS), can trigger emotional and cognitive dysfunctions in adulthood similar to those found in humans with a history of childhood adversity. The magnitude of IMS effects differs among diverse inbred strains suggesting an interaction between the genetic background of pups and the maternal care they received. Here, we investigated this interaction with studies on reciprocal F1 hybrid mice of the stress-susceptible Balb/c and the resilient C57Bl/6 strains that were either raised by Balb/c mothers (low maternal care) or by C57Bl/6 mothers (higher maternal care) with or without IMS exposure. The ultrasonic vocalization response to isolation was recorded from infant F1 pups, and their emotional, executive cognitive and epigenetic phenotypes were assessed in adulthood. These studies showed that, regardless of the maternal care received, the emotional phenotype of F1 hybrids was not significantly affected by IMS exposure. However, F1 pups raised by Balb/c (but not C57Bl/6) mothers during IMS exposure exhibit deficits in working memory and attention-set-shifting in adulthood. They also exhibit reduced histone deacetylase 1 levels at promotors of brain-derived neurotrophic factor and early growth response 2 genes, and abnormally high induction of expression of these genes during cognitive testing. As one of affected genes was previously shown to associate with the Balb/c and the other with the C57Bl/6 genetic background, these findings indicate that both parental alleles interact with the maternal environment to modulate the cognitive and epigenetic phenotypes of F1 mice exposed to the IMS.

Mother and offspring fitness in an insect with maternal care: phenotypic trade-offs between egg number, egg mass and egg care.

BackgroundOviparous females have three main options to increase their reproductive success: investing into egg number, egg mass and/or egg care. Although allocating resources to either of these three components is known to shape offspring number and size, potential trade-offs among them may have key impacts on maternal and offspring fitness. Here, we tested the occurrence of phenotypic trade-offs between egg number, egg mass and maternal expenditure on egg care in the European earwig, Forficula auricularia, an insect with pre- and post-hatching forms of maternal care. In particular, we used a series of laboratory observations and experiments to investigate whether these three components non-additively influenced offspring weight and number at hatching, and whether they were associated with potential costs to females in terms of future reproduction.ResultsWe found negative associations between egg number and mass as well as between egg number and maternal expenditure on egg care. However, these trade-offs could only be detected after statistically correcting for female weight at egg laying. Hatchling number was not determined by single or additive effects among the three life-history traits, but instead by pairwise interactions among them. In particular, offspring number was positively associated with the number of eggs only in clutches receiving high maternal care or consisting of heavy eggs, and negatively associated with mean egg mass in clutches receiving low care. In contrast, offspring weight was positively associated with egg mass only. Finally, maternal expenditure on egg care reduced their future reproduction, but this effect was only detected when mothers were experimentally isolated from their offspring at egg hatching.ConclusionsOverall, our study reveals simultaneous trade-offs between the number, mass and care of eggs. It also demonstrates that these factors interact in their impact on offspring production, and that maternal expenditure on egg care possibly shapes female future reproduction. These findings emphasize that studying reproductive success requires consideration of phenotypic trade-offs between egg-number, egg mass and egg care in oviparous species.

It Takes Two: Sensitive Caregiving Across Contexts and Children's Social, Emotional, and Academic Outcomes

Research Findings: Using longitudinal survey data from the Welfare, Children, and Families Study: A Three-City Study (n = 135), this study examines how congruence in maternal and child care provider sensitivities contributes to young children's social, emotional, and academic outcomes among low-income minority families. Congruence groups were created based on levels of high and low maternal and child care provider sensitivity. Children with high maternal sensitivity and low child care provider sensitivity had lower scores on measures of social competence and applied problems compared to children with high maternal and child care provider sensitivity. Children with low maternal sensitivity but high child care provider sensitivity displayed higher emotional competence than children with low maternal and child care sensitivity, implying an important protective benefit of child care. Practice or Policy: Current state and federal policy climates, including recently awarded Early Learning Challenge grants focused on social and personal development and the Academic, Social, and Emotional Learning Act, reflect an important emphasis on social and emotional learning. Given this, the findings from this study implicate the role of families and child care providers as important components in any policy or program focused on shaping children's early social and emotional outcomes.

Predictors for exacerbation/improvement of postpartum depression—A focus on anxiety, the mothers' experiences of being cared for by their parents in childhood and borderline personality: A perspective study in Japan

ObjectiveTo investigate the course and influencing factors of postpartum depression in women during the child rearing period. MethodsData were collected during 0-year-old baby check-ups and a follow-up investigation. 262 participants were included in the analysis. Both surveys employed the Zung Self-Rating Depression Scale (ZSDS). The first also comprised the State Trait Anxiety Inventory, Parental Bonding Instrument (PBI), and Borderline Scale Index, enabling sub-division of participating subjects into healthy/pathological groups. ZSDS group and survey scores were compared using the t-test. ResultsThe average ages of the children and the ZSDS scores in both surveys were 7.0±3.2 and 21.8±2.4 months, 40.6±7.9 and 40.1±8.7, respectively, with no significant differences among depression scores. When subjects were divided according to individual scale scores, and survey scores compared, depression significantly improved in the high trait/state anxiety group, high PBI maternal care score group, nonborderline personality (BP) trait group, and breast feeding group, whereas depression was significantly exacerbated in the low PBI maternal care score group. DiscussionPostpartum depression characterized by strong anxiety and a depressive state in mothers with favorable psychological backgrounds showed gradual improvement. We noted an exacerbation of depression during the separation period in mothers who had received poor maternal care. We assume that the feeling of abandonment induced by individuation of their children is a major factor. LimitationsThere is concern that some depressive women may have dropped out due to a performance bias. ConclusionsSharing our findings about exacerbation/improvement of depression among medical staff may be beneficial for postpartum mothers.

Sub-optimal parenting is associated with schizotypic and anxiety personality traits in adulthood

Part of the variation in personality characteristics has been attributed to the child–parent interaction and sub-optimal parenting has been associated with psychiatric morbidity. In the present study, an extensive battery of personality scales (Trait Anxiety Inventory, Behavioural Inhibition/Activation System questionnaire, Eysenck Personality Questionnaire-Revised, Temperament and Character Inventory, Schizotypal Traits Questionnaire, Toronto Alexithymia Scale) and the Parental Bonding Instrument (PBI) were administered in 324 adult healthy males to elucidate the effects of parenting on personality configuration. Personality variables were analysed using Principal Component Analysis (PCA) and the factors “Schizotypy”, “Anxiety”, “Behavioural activation”, “Novelty seeking” and “Reward dependence” were extracted. Associations between personality factors with PBI “care” and “overprotection” scores were examined with regression analyses. Subjects were divided into “parental style” groups and personality factors were subjected to categorical analyses. “Schizotypy” and “Anxiety” were significantly predicted by high maternal overprotection and low paternal care. In addition, the Affectionless control group (low care/high overprotection) had higher “Schizotypy” and “Anxiety” compared with the Optimal Parenting group (high care/low overprotection). These results further validate sub-optimal parenting as an important environmental exposure and extend our understanding on the mechanisms by which it increases risk for psychiatric morbidity.

DATby perceived MC interaction on human prefrontal activity and connectivity during emotion processing

Maternal care (MC) and dopamine modulate brain activity during emotion processing in inferior frontal gyrus (IFG), striatum and amygdala. Reuptake of dopamine from the synapse is performed by the dopamine transporter (DAT), whose abundance is predicted by variation in its gene (DAT 3'VNTR; 10 > 9-repeat alleles). Here, we investigated the interaction between perceived MC and DAT 3'VNTR genotype on brain activity during processing of aversive facial emotional stimuli. Sixty-one healthy subjects were genotyped for DAT 3'VNTR and categorized in low and high MC individuals. They underwent functional magnetic resonance imaging while performing a task requiring gender discrimination of facial stimuli with angry, fearful or neutral expressions. An interaction between facial expression, DAT genotype and MC was found in left IFG, such that low MC and homozygosity for the 10-repeat allele are associated with greater activity during processing of fearful faces. This greater activity was also inversely correlated with a measure of emotion control as scored with the Big Five Questionnaire. Moreover, MC and DAT genotype described a double dissociation on functional connectivity between IFG and amygdala. These findings suggest that perceived early parental bonding may interact with DAT 3'VNTR genotype in modulating brain activity during emotionally relevant inputs.

Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity

BackgroundIn the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats. MethodExperiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life.Experiment II: rat pups exposed as neonates to daily sessions of 8h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions.Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments. ResultsExperiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For demonstration of the cumulative stress hypothesis an injection of CORT in the adult Low LG offspring was required that increased APO-gnawing and reduced PPI. This CORT-induced PPI disruption was greatly enhanced after additional isolation rearing. The High LG group, either socially housed or reared in isolation, was resistant to the acute effects of CORT at adulthood.Experiment II: MS increased psychosis susceptibility only in NOVEL SEP rats that had experienced MS in the context of early social isolation. These individuals displayed increased adult APO-gnawing and reduced PPI, if reared post-weaning in a condition that does not match with their early life social environment (i.e. group housing). This finding supports the mismatch hypothesis. ConclusionThe outcome of environmental manipulations on developmental programming of psychosis susceptibility depends on the interplay of early-life adversity and later-life stressors in a manner that supports the mismatch hypothesis. However, evidence for the cumulative stress hypothesis arises if vulnerable individuals are exposed in later life additionally to excess of the stress hormone CORT.