scholarly journals Effects of early life adversity on immediate early gene expression: Systematic review and 3-level meta-analysis of rodent studies

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0253406
Author(s):  
Heike Schuler ◽  
Valeria Bonapersona ◽  
Marian Joëls ◽  
R. Angela Sarabdjitsingh

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA (alteration of maternal care) on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced additional hits. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.

2021 ◽  
Author(s):  
Heike Schuler ◽  
Valeria Bonapersona ◽  
Marian Joels ◽  
Ratna Angela Sarabdjitsingh

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced multiple negative life events. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naive, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.


Author(s):  
Jack M. Gorman

Psychiatry downplayed the importance of life events in causing mental illness from the 1960s on, favoring a view that all disorders except one are the result of abnormal genes affecting chemical processes in the brain. Studying the exception, posttraumatic stress disorder (PTSD), when it was defined in 1980 helped lead to renewed recognition that early life adversity is central to all psychiatric conditions. At the same time, neuroscientists showed that early life experiences are capable of changing life-long behavior and brain function in laboratory animals. One mechanism by which this occurs is through the epigenetic regulation of gene expression. Epigenetics is the way that the expression levels of genes are controlled without changing the underlying genetic code. Epigenetics is an attractive way of understanding how individual life experiences are translated in the brain into each person’s unique set of emotions, behaviors, abilities, and risks for psychiatric abnormalities.


2021 ◽  
pp. 088626052110572
Author(s):  
Jordan L. Thomas ◽  
Danielle Keenan-Miller ◽  
Jennifer A. Sumner ◽  
Constance Hammen

Intimate partner violence (IPV) is associated with adverse outcomes for both victims and perpetrators, though there is significant heterogeneity in manifestations of relationship violence. A growing amount of research has focused on elucidating predictors of clinical IPV—defined as severe violence involving institutional or medical intervention due to actual or potential injury—so as to better understand potential prevention and intervention targets. Early life adversity (ELA) is associated with IPV in adulthood, yet this literature focuses on discrete, retrospectively reported adversities (e.g., physical abuse and neglect) and has yet to consider clinical IPV as an outcome. Little is known about if and how broadly adverse early environments may confer risk for this specific form of relationship violence. We investigated associations between exposure to ELA prior to age five and clinical IPV victimization and perpetration by age 20 in a longitudinal, community-based sample of men and women in Australia ( N = 588). Early life adversity was prospectively indexed by maternal reports of financial hardship, child chronic illness, maternal stressful life events, maternal depressive symptoms, parental discord, and parental separation. Youth interpersonal conflict life events at age 15—an interviewer-rated assessment of episodic stressors involving conflict across relationships in mid-adolescence—was tested as a potential mediator for both victims and perpetrators. Among women, ELA predicted IPV victimization and perpetration, and interpersonal conflict life events partially mediated the link between ELA and victimization, but not perpetration. Neither ELA nor interpersonal conflict life events predicted victimization or perpetration among men. Women exposed to ELA are at-risk for conflictual interpersonal relationships later in life, including violent intimate relationships, and deficits in conflict resolution skills may be one mechanism through which ELA leads to IPV victimization among this subgroup. Violence prevention and intervention efforts should target interpersonal skills, including conflict resolution, among women and girls exposed to adverse early environments.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yaoyao Bian ◽  
Lili Yang ◽  
Zhongli Wang ◽  
Qing Wang ◽  
Li Zeng ◽  
...  

Adverse early life experiences can negatively affect behaviors later in life. Maternal separation (MS) has been extensively investigated in animal models in the adult phase of MS. The study aimed to explore the mechanism by which MS negatively affects C57BL/6N mice, especially the effects caused by MS in the early phase. Early life adversity especially can alter plasticity functions. To determine whether adverse early life experiences induce changes in plasticity in the brain hippocampus, we established an MS paradigm. In this research, the mice were treated with mild (15 min, MS15) or prolonged (180 min, MS180) maternal separation from postnatal day 2 to postnatal day 21. The mice underwent a forced swimming test, a tail suspension test, and an open field test, respectively. Afterward, the mice were sacrificed on postnatal day 31 to determine the effects of MS on early life stages. Results implied that MS induces depression-like behavior and the effects may be mediated partly by interfering with the hippocampal GSK-3β-CREB signaling pathway and by reducing the levels of some plasticity-related proteins.


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