Early-Life Stress and Psychiatric Disorders: Epidemiology, Neurobiology and Innovative Pharmacological Targets

2015 ◽  
Vol 21 (11) ◽  
pp. 1379-1387 ◽  
Author(s):  
A. Ventriglio ◽  
A. Gentile ◽  
R.J. Baldessarini ◽  
A. Bellomo
2021 ◽  
Vol 22 (2) ◽  
pp. 730
Author(s):  
Anna Portugalov ◽  
Irit Akirav

There have been growing concerns about the protracted effects of cannabis use in adolescents on emotion and cognition outcomes, motivated by evidence of growing cannabis use in adolescents, evidence linking cannabis use to various psychiatric disorders, and the increasingly perceived notion that cannabis is harmless. At the same time, studies suggest that cannabinoids may have therapeutic potential against the impacts of stress on the brain and behavior, and that young people sometimes use cannabinoids to alleviate feelings of depression and anxiety (i.e., “self-medication”). Exposure to early adverse life events may predispose individuals to developing psychopathology in adulthood, leading researchers to study the causality between early life factors and cognitive and emotional outcomes in rodent models and to probe the underlying mechanisms. In this review, we aim to better understand the long-term effects of cannabinoids administered in sensitive developmental periods (mainly adolescence) in rodent models of early life stress. We suggest that the effects of cannabinoids on emotional and cognitive function may vary between different sensitive developmental periods. This could potentially affect decisions regarding the use of cannabinoids in clinical settings during the early stages of development and could raise questions regarding educating the public as to potential risks associated with cannabis use.


2021 ◽  
Vol 13 ◽  
Author(s):  
Ryan D. Shepard ◽  
Fereshteh S. Nugent

Adverse events and childhood trauma increase the susceptibility towards developing psychiatric disorders (substance use disorder, anxiety, depression, etc.) in adulthood. Although there are treatment strategies that have utility in combating these psychiatric disorders, little attention is placed on how to therapeutically intervene in children exposed to early life stress (ELS) to prevent the development of later psychopathology. The lateral habenula (LHb) has been a topic of extensive investigation in mental health disorders due to its prominent role in emotion and mood regulation through modulation of brain reward and motivational neural circuits. Importantly, rodent models of ELS have been shown to promote LHb dysfunction. Moreover, one of the potential mechanisms contributing to LHb neuronal and synaptic dysfunction involves endocannabinoid (eCB) signaling, which has been observed to critically regulate emotion/mood and motivation. Many pre-clinical studies targeting eCB signaling suggest that this neuromodulatory system could be exploited as an intervention therapy to halt maladaptive processes that promote dysfunction in reward and motivational neural circuits involving the LHb. In this perspective article, we report what is currently known about the role of eCB signaling in LHb function and discuss our opinions on new research directions to determine whether the eCB system is a potentially attractive therapeutic intervention for the prevention and/or treatment of ELS-associated psychiatric illnesses.


2014 ◽  
Vol 16 (1) ◽  
pp. 29-41 ◽  

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants.


2021 ◽  
Vol 8 ◽  
Author(s):  
Carlos A. González-Acosta ◽  
Christian A. Rojas-Cerón ◽  
Efraín Buriticá

Early life stress can be caused by acute or chronic exposure to childhood events, such as emotional, physical, sexual abuse, and neglect. Early stress is associated with subsequent alterations in physical and mental health, which can extend into adolescence, adulthood, and even old age. The effects of early stress exposure include alterations in cognitive, neuropsychological, and behavioral functions, and can even lead to the development of psychiatric disorders and changes in brain anatomy. The present manuscript provides a review of the main findings on these effects reported in the scientific literature in recent decades. Early life stress is associated with the presence of psychiatric disorders, mainly mood disorders such as depression and risk of suicide, as well as with the presence of post-traumatic stress disorder. At the neuropsychological level, the involvement of different mental processes such as executive functions, abstract reasoning, certain memory modalities, and poor school-skill performance has been reported. In addition, we identified reports of alterations of different subdomains of each of these processes. Regarding neuroanatomical effects, the involvement of cortical regions, subcortical nuclei, and the subcortical white matter has been documented. Among the telencephalic regions most affected and studied are the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. Understanding the impact of early life stress on postnatal brain development is very important for the orientation of therapeutic intervention programs and could help in the formulation and implementation of preventive measures as well as in the reorientation of research targets.


2013 ◽  
Vol 201 (12) ◽  
pp. 1007-1020 ◽  
Author(s):  
Clara Passmann Carr ◽  
Camilla Maria Severi Martins ◽  
Ana Maria Stingel ◽  
Vera Braga Lemgruber ◽  
Mario Francisco Juruena

2017 ◽  
Vol 1 ◽  
pp. 247054701769446 ◽  
Author(s):  
Shariful A. Syed ◽  
Charles B. Nemeroff

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health’s proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.


2016 ◽  
Vol 6 (11) ◽  
pp. e943-e943 ◽  
Author(s):  
A Luoni ◽  
R Massart ◽  
V Nieratschker ◽  
Z Nemoda ◽  
G Blasi ◽  
...  

2020 ◽  
Author(s):  
Eamon Fitzgerald ◽  
Matthew C Sinton ◽  
Sara Wernig-Zorc ◽  
Nicholas M Morton ◽  
Megan C Holmes ◽  
...  

AbstractEarly life stress during childhood is associated with a number of psychiatric disorders that manifest across the life course. Preterm birth is a profound stressor, and an important cause of cognitive impairment, as well as neurodevelopmental and psychiatric disorders. However, the mechanisms that link events during the early neonatal period with later functional problems are poorly understood. We developed a novel mouse model of early life stress (modified maternal separation; MMS) with specific relevance to preterm birth (PTB) and hypothesised it would affect the hypothalamic transcriptome and DNA methylome and impact on behaviour in adulthood. MMS consisted of repeatedly stimulating pups for 1.5 hours/day, whilst separated from their mother, from postnatal day (P)4-6. 3’ RNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing was performed on the hypothalamus at P6. Behaviour was assessed with the elevated plus and open field mazes, and in-cage monitoring at 3-4 months of age. Although MMS was only associated with subtle changes in gene expression there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS also resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. In conclusion we describe a novel model of early life stress with relevance to PTB, with marked effects on DNA methylation in the hypothalamus and with stress-specific hyperactivity in young adulthood. We suggest that these results have implications for the understanding of early life stress mediated effects on brain development.


2020 ◽  
Vol 8 ◽  
pp. 100120
Author(s):  
Annamaria Cattaneo ◽  
Nadia Cattane ◽  
Catia Scassellati ◽  
Ilari D’Aprile ◽  
Marco Andrea Riva ◽  
...  

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