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Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations.

ABSTRACT: While effects of gestational, neonatal or adolescent stress on psychological alterations in progeny have been extensively studied, much less is known regarding the effects of adult pre-gestational life events on offspring behavior. Although full siblings often display behavioral differences, whether the different parental life events prior to different pregnancies contribute to these behavioral differences among siblings is worth studying. In this study, male and female adult mice were restrained for 60 days before mating with unstressed or stressed partners. F1 offspring were examined for anxiety or mated to generate F2. Both F1 females and males from restrained mothers and/or fathers showed significantly reduced anxiety and serum cortisol and increased mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor compared to control offspring from unstressed parents. Similar behavioral and molecular changes were also observed in F2 females and males. Although restraint of adolescent mice reduced anxiety in F1 of both sexes, social instability of them increased anxiety predominantly in F1 females. Thus, adult pre-gestational restraint reduced offspring's anxiety across generations; different stressors on parents may cause different phenotypes in offspring; individual behaviors can depend on adult life experiences of parents.

SUBMITTER: He N

PROVIDER: S-EPMC5175168 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations.

He Nan N Kong Qiao-Qiao QQ Wang Jun-Zuo JZ Ning Shu-Fen SF Miao Yi-Long YL Yuan Hong-Jie HJ Gong Shuai S Cui Xiang-Zhong XZ Li Chuan-Yong CY Tan Jing-He JH

Scientific reports 20161221

While effects of gestational, neonatal or adolescent stress on psychological alterations in progeny have been extensively studied, much less is known regarding the effects of adult pre-gestational life events on offspring behavior. Although full siblings often display behavioral differences, whether the different parental life events prior to different pregnancies contribute to these behavioral differences among siblings is worth studying. In this study, male and female adult mice were restraine ...[more]

PMID: 28000794

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Project description:ObjectiveThe majority of studies that have examined parental alcohol use and offspring outcomes have either focused on exposure in the antenatal period or from clinical populations. This study sought to examine proximal and distal associations between parental alcohol use and offspring conduct problems and depressive symptoms in a population birth cohort.MethodsWe used prospective data from a large UK based population cohort (ALSPAC) to investigate the association between parental alcohol use, measured in units, (assessed at ages 4 and 12 years) with childhood conduct trajectories, (assessed on six occasions from 4 to 13.5 years, n = 6,927), and adolescent depressive symptoms (assessed on four occasions from ~13 to ~18 years, n = 5,539). Heavy drinking was defined as ?21 units per week in mothers and partners who drank 4+ units daily.ResultsWe found little evidence to support a dose response association between parental alcohol use and offspring outcomes. For example, we found insufficient evidence to support an association between maternal alcohol use at age 4 years and childhood conduct problems (childhood limited: OR = 1.00, 95% CI = .99, 1.01; adolescent onset: OR = 0.99, 95% CI = .98, 1.00; and early-onset persistent: OR = 0.99, 95% CI = .98, 1.00) per 1-unit change in maternal alcohol use compared to those with low levels of conduct problems. We also found insufficient evidence to support an association between maternal alcohol use at age 4 years and adolescent depressive symptoms (intercept: b = .001, 95% CI = -.01, .01, and slope: b = .003, 95% CI = -.03, .03) per 1-unit change in maternal alcohol use. Results remained consistent across amount of alcohol consumed (i.e., number of alcohol units or heavy alcohol use), parent (maternal self-reports or maternal reports of partner's alcohol use), and timing of alcohol use (assessed at age 4 or age 12 years).ConclusionsThere is no support for an association between parental alcohol use during childhood and conduct and emotional problems during childhood or adolescence.

Project description:A fundamental tenet of maternal effects assumes that maternal variance over time should have discordant consequences for offspring traits across litters. Yet, seldom are parents observed across multiple reproductive bouts, with few studies considering anthropogenic disturbances as an ecological driver of maternal effects. We observed captive coyote (Canis latrans) pairs over two successive litters to determine whether among-litter differences in behavior (i.e., risk-taking) and hormones (i.e., cortisol and testosterone) corresponded with parental plasticity in habituation. Thus, we explicitly test the hypothesis that accumulating experiences of anthropogenic disturbance reduces parental fear across reproductive bouts, which should have disparate phenotypic consequences for first- and second-litter offspring. To quantify risk-taking behavior, we used foraging assays from 5-15 weeks of age with a human observer present as a proxy for human disturbance. At 5, 10, and 15 weeks of age, we collected shaved hair to quantify pup hormone levels. We then used a quantitative genetic approach to estimate heritability, repeatability, and between-trait correlations. We found that parents were riskier (i.e., foraged more frequently) with their second versus first litters, supporting our prediction that parents become increasingly habituated over time. Second-litter pups were also less risk-averse than their first-litter siblings. Heritability for all traits did not differ from zero (0.001-0.018); however, we found moderate support for repeatability in all observed traits (r = 0.085-0.421). Lastly, we found evidence of positive phenotypic and cohort correlations among pup traits, implying that cohort identity (i.e., common environment) contributes to the development of phenotypic syndromes in coyote pups. Our results suggest that parental habituation may be an ecological cue for offspring to reduce their fear response, thus emphasizing the role of parental plasticity in shaping their pups' behavioral and hormonal responses toward humans.

Project description:22q11.2 deletion syndrome (22q11DS) is recognized as one of the strongest genetic risk factors for the development of psychopathology, including dramatically increased prevalence of schizophrenia anxiety disorders, mood disorders, and Attention Deficit Hyperactivity Disorder (ADHD). Despite sharing a homogenous genetic deletion, the psychiatric phenotype in 22q11DS still present significant variability across subjects. The origins of such variability remain largely unclear. Levels of parental psychopathology could significantly contribute to phenotypic variability of offspring psychopathology, through mechanisms of gene x gene (GxG) and gene x environment (GxE) interactions. However, this hypothesis has not been explicitly tested to date in 22q11DS. In the present manuscript, we employed a longitudinal design to investigate bi-directional interactions of parental anxiety and depressive symptoms, estimated with Beck Depression Inventory and Beck Anxiety Inventory, and offspring level of psychopathology assessed with a combination of parentally reported Child Behavioral Checklist, Youth Self Report Questionnaire, and Structured Clinical Interviews for Prodromal Syndromes (SIPS). We tested associations in both typically developing healthy controls (HCs) (N = 88 participants; N = 131 time points) and in individuals with 22q11DS (N = 103 participants; N = 198 time points). We observed that 22q11DS individuals with higher levels of parental anxiety and depression presented significant increases in multiple forms of psychopathology, including higher internalizing and externalizing symptoms, as estimated both by parental and self-report questionnaires, along with higher negative and generalized symptoms as measured with the SIPS. Associations for positive and disorganized dimensions of the SIPS were not statistically significant. Purely longitudinal analysis pointed to bi-directional interactions of parental and child psychopathology, with marginally stronger longitudinal associations between early parental anxiety-depression and subsequent child psychopathology. Interestingly, associations between psychopathology across generations were significantly stronger in 22q11DS individuals compared to HCs. Our results show that parental levels of anxiety and depression are associated with levels of offspring psychopathology, particularly in individuals with 22q11DS. These findings point to the existence of GxG or GxE mechanisms, that should be investigated in future work. From a clinical perspective, they highlight a strong rational for the management of parental psychological well-being in 22q11DS.

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Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations.

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Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations.

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