Inflammatory biomarkers in individuals exposed to early life stress: a systematic review and meta-analysis

Objective:The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.Methods:We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms:child abuse,depression,HPA axis,dexamethasone,prednisolone,fludrocortisoneandspironolactone. Thirty-four papers were selected for this review.Results:Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.Conclusions:The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

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Analysis of the occurrence of early life stress in adult psychiatric patients: A systematic review.

Psychology & Neuroscience ◽

10.3922/j.psns.2011.2.007 ◽

2011 ◽

Vol 4 (2) ◽

pp. 219-227 ◽

Cited By ~ 29

Author(s):

Camila Maria Severi Martins ◽

Sandra Marcia de Carvalho Tofoli ◽

Cristiane Von Werne Baes ◽

Mario Juruena

Keyword(s):

Systematic Review ◽

Life Stress ◽

Early Life ◽

Psychiatric Patients ◽

Early Life Stress

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Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis

Translational Psychiatry ◽

10.1038/s41398-021-01352-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mariana Rocha ◽

Daniel Wang ◽

Victor Avila-Quintero ◽

Michael H. Bloch ◽

Arie Kaffman

Keyword(s):

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Dorsal Hippocampus ◽

Meta Analysis ◽

Early Life Stress ◽

Ventral Hippocampus ◽

Contextual Fear Conditioning ◽

Rodent Models ◽

Improved Performance

AbstractExposure to early life stress (ELS) causes abnormal hippocampal development and functional deficits in rodents and humans, but no meta-analysis has been used yet to quantify the effects of different rodent models of ELS on hippocampal-dependent memory. We searched PubMed and Web of Science for publications that assessed the effects of handling, maternal separation (MS), and limited bedding and nesting (LBN) on performance in the Morris water maze (MWM), novel object recognition (NOR), and contextual fear conditioning (CFC). Forty-five studies met inclusion criteria (n = 451–763 rodents per test) and were used to calculate standardized mean differences (Hedge’s g) and to assess heterogeneity, publication bias, and the moderating effects of sex and species (rats vs. mice). We found significantly lower heterogeneity in LBN compared to handling and MS with no consistent effects of sex or species across the three paradigms. LBN and MS caused similar cognitive deficits in tasks that rely heavily on the dorsal hippocampus, such as MWM and NOR, and were significantly different compared to the improved performance seen in rodents exposed to handling. In the CFC task, which relies more on the ventral hippocampus, all three paradigms showed reduced freezing with moderate effect sizes that were not statistically different. These findings demonstrate the utility of using meta-analysis to quantify outcomes in a large number of inconsistent preclinical studies and highlight the need to further investigate the possibility that handling causes different alterations in the dorsal hippocampus but similar outcomes in the ventral hippocampus when compared to MS and LBN.

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Early-life stress and inflammation: A systematic review of a key experimental approach in rodents

Brain and Neuroscience Advances ◽

10.1177/2398212820978049 ◽

2020 ◽

Vol 4 ◽

pp. 239821282097804

Author(s):

Ethan G. Dutcher ◽

E.A. Claudia Pama ◽

Mary-Ellen Lynall ◽

Shahid Khan ◽

Menna R. Clatworthy ◽

...

Keyword(s):

Systematic Review ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Later Life ◽

Interleukin 10 ◽

Brain Regions ◽

Clinical Approach ◽

Necrosis Factor Alpha

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.

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