Association of the World War II Finnish Evacuation of Children With Psychiatric Hospitalization in the Next Generation

Santavirta, Torsten; Santavirta, Nina; Gilman, Stephen E.

doi:10.1001/jamapsychiatry.2017.3511

Cited by 35 publications

(17 citation statements)

References 42 publications

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“…Moreover, offspring of those exposed to early life trauma are at elevated risk for psychiatric disorders 9 . This phenomena has also been demonstrated in rodents 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Dickson¹,

et al. 2018

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Exposure of male mice to early life stress alters the levels of specific sperm miRNAs that promote stress-associated behaviors in their offspring. To begin to evaluate whether similar phenomena occur in men, we searched for sperm miRNA changes that occur in both mice and men exposed to early life stressors that have long-lasting effects. For men, we used the Adverse Childhood Experience (ACE) questionnaire. It reveals the degree of abusive and/or dysfunctional family experiences when young, which increases risks of developing future psychological and physical disorders. For male mice, we used adolescent chronic social instability (CSI) stress, which not only enhances sociability defects for >1 year, but also anxiety and defective sociability in female offspring for multiple generations through the male lineage. Here we found a statistically significant inverse correlation between levels of multiple miRNAs of the miR-449/34 family and ACE scores of Caucasian males. Remarkably, we found members of the same sperm miRNA family are also reduced in mice exposed to CSI stress. Thus, future studies should be designed to directly test whether reduced levels of these miRNAs could be used as unbiased indicators of current and/or early life exposure to severe stress. Moreover, after mating stressed male mice, these sperm miRNA reductions persist in both early embryos through at least the morula stage and in sperm of males derived from them, suggesting these miRNA changes contribute to transmission of stress phenotypes across generations. Since offspring of men exposed to early life trauma have elevated risks for psychological disorders, these findings raise the possibility that a portion of this risk may be derived from epigenetic regulation of these sperm miRNAs.

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“…Moreover, offspring of those exposed to early life trauma are at elevated risk for psychiatric disorders 9 . This phenomena has also been demonstrated in rodents 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Dickson¹,

et al. 2018

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“…The multi-generational stress resembles human populations living in chronic stress conditions, e.g., several generations exposed to residential school, war or poverty. (Laplante et al, 2016) (Santavirta et al, 2017) Compared to single-generation PS, the multigenerational stress has somewhat different consequences: it facilitates adaptation to the recurrent maternal stress across generations, thus generating stress resilience. This causes new behavioral traits and better brain activity coherence.…”

Section: B) Multi-generational Studiesmentioning

confidence: 99%

Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis

Frasch

Lobmaier

Stampalija

et al. 2020

Neuroscience & Biobehavioral Reviews

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Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.

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“…Similarly, genocide exposure in Cambodia and Rwanda has been linked to increased hyper-arousal and anxiety and depression in descendants, respectively [28,29]. The offspring of veterans of Serbian-Bosnian war with PTSD also have neurodevelopmental delays and emotional deficits [30] while daughters of Finnish women evacuated during the Second World War have increased risk of psychiatric hospitalization [31]. A very recent study examined the sperm of men with adverse childhood experiences and showed alterations in some miR-NAs that are similar to that observed in mice exposed to stress and their offspring [32 ].…”

Section: Inter-and Transgenerational Epigenetic Inheritance Of Negatimentioning

confidence: 99%

“…Yehuda et al [27 ] Genocide exposure in Cambodia Increased anxiety in the offspring Field et al [28] Genocide exposure in Rwanda Increased anxiety and depression in the offspring Rieder and Elbert [29] Evacuation during the second world war in Finland Increase psychiatric hospitalizations in women whose mothers were evacuated Santavirta et al [31] germ cells [34 ]. EE has also been shown to allow the correction of LTP and fear memory deficits in the offspring of Ras-GRF knock out mice [33] and to reverse the co-morbid anxiety in the offspring of a genetic model of absence seizures in mice [35].…”

Section: Exposure Associated Inherited Behavioral Phenotype Referencementioning

confidence: 99%

Inter- and transgenerational inheritance of behavioral phenotypes

Jawaid

Mansuy

2019

Current Opinion in Behavioral Sciences

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Adult animal behaviors are determined by complex and dynamic changes in gene expression in different brain regions and are influenced by life experiences and environmental exposures. These stimuli affect gene expression through intricate mechanisms of regulation that largely implicate epigenetic factors, such as, DNA methylation, histone post-translational modifications, and non-coding RNAs (ncRNAs). Through these molecular pathways, some of the behavioral phenotypes associated with life experiences can be stably transmitted to descendants, sometimes across several generations. Rodent studies indicate that parental stressful and traumatic experiences can lead to behavioral despair, risk-taking behaviors, altered sociability and atypical responses to stressful stimuli in the offspring, whereas parental environmental enrichment has been associated with improved cognition and stress resilience in the offspring. Similar observations have been made in humans; children and grandchildren of genocide survivors show increased psychopathology and emotional disturbances. At the molecular level, changes in germline ncRNAs have been identified as likely vectors of transmission in rodents. The mechanisms linking behavioral stimuli to the germline, and factors responsible for these changes and their persistence across generations remain, however, largely unidentified.

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Association of the World War II Finnish Evacuation of Children With Psychiatric Hospitalization in the Next Generation

Cited by 35 publications

References 42 publications

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis

Inter- and transgenerational inheritance of behavioral phenotypes

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