Scientia
IN-DEPTH
Long-lasting Effects of Early Life Stress on the Brain and Epigenome Omar Kassem Abstract Stable caregiving in early life is critical for normal social and emotional development. Exposure to chronic or extreme stress early in life has been associated with increased risk for psychiatric disorders, especially affective disorders. Early life stress (ELS) has long-lasting impacts on the development and function of diverse brain regions that are involved in emotional processing, cognitive functions, and social behavior. Despite the adverse effects of ELS on brain development, the neural underpinnings of those effects are not yet well characterized. This review highlights ELS-provoked changes in networks wiring, the cellular impacts on neuron excitability and myelination, and the epigenetic modifications that contribute to those changes. Understanding those neurobiological aberrations aids in understanding the increased risk for psychopathology that has been reported in children exposed to ELS and provides insights into potential Introduction
have revealed that ELS can provoke changes conducted on adolescents years after exposure
Brain development and maturation on various levels including changes in neuron but the impact of ELS was still significant. Further are modulated by an interaction between excitability
and
myelination,
rewiring
of studies in mice have provided more insight into
environmental inputs and genes. It is well networks, and epigenetic modifications that are the underlying neural changes in those regions established that exposure to stress at different in some cases transgenerational [2,9,10,11]. Thus, in response to stress. The main physiological ages leads to different outcomes, with early stages integrating findings from circuitry, cellular, and model of memory formation in the brain is of development being associated with more severe genetic studies is essential to fully understand through adjusting synaptic weights in networks and long-lasting effects [1]. Early childhood is this
process.
Understanding
the
neural to encode memories. Several studies have
a critical period of brain development, which underpinnings of the relationship between ELS demonstrated that ELS interferes with synaptic renders it highly vulnerable to disorganizing and the mental health of the victims is of great plasticity and induces dendritic as well as spine environmental influences. Sustained or adverse value in the pursuit of possible treatments and atrophy [13,16,17]. The cumulative effect of these early-life stress (ELS), such as childhood trauma or interventions. Moreover, a better understanding alterations causes the loss of functional synapses, caregiver deprivation, modifies the expression of of caregiver-related stress effects on child which contributes to cognitive deficits. These multiple neurotransmitters and other molecules development provides many useful insights for influences on neural networks are mediated by that affect neuron and network development improving orphanage systems.
multiple molecules including stress-associated
in specific brain regions, potentially causing
glucocorticoid hormones, neurotransmitters,
long-term structural and functional changes [2]. Impact of ELS through disruption of the and neuropeptides. Better characterization of Brain regions involved in emotional processing, maturation of brain networks and circuitry such as the amygdala, cognitive regions such as
the stress toolbox has enhanced our ability to
The long-term effects of ELS stem pharmacologically intervene and manage stress
the hippocampus and prefrontal cortex, as well from the fact that developmental processes that symptoms [18,19]. as networks involved in social behaviors seem organize circuits and connectivity patterns are
Similarly, ELS, especially in the form
to be particularly responsive and vulnerable still occurring. In humans, the development of of caregiver deprivation, has been shown to to the impact of stress [1,3,4,5,6]. ELS-induced the hippocampus and limbic circuit, which are affect the development of the amygdala, which is long-lasting changes in these regions would be involved in cognitive and emotional functions, highly involved in emotion processing, affective expected to increase susceptibility to emotional takes place largely shortly after birth and valuation, and learning [20]. One key study did disorders and psychiatric illnesses, which has continues for years into adolescence. Therefore, an fMRI scan of brain activity of children adopted been reported in many epidemiological human unlike the effects of stress on adult cognitive from orphanages in a behavioral paradigm where studies [7,8]. Although the associations that functions that are reversible, ELS can often they were instructed to “go” to a neutral cue, and were statistically inferred from epidemiological permanently impact these processes and systems, “not go” to a rare threat cue [3]. Results showed studies are highly indicative of the impact of ELS, yet behavioral and pharmacological interventions that ELS-exposed preadolescents took longer it is difficult to prove causality and elucidate the can still be effective [12,13,14].. An epidemiological to approach a cue when anticipating a potential biological mechanisms underlying this influence study
conducted
on
post-institutionalized threat, indicating that the disorganized care of
in humans. Therefore, many subsequent studies adolescents showed that chronic early life the orphanage experience can alter emotional have used animal models to investigate the stress, being raised in orphanages, is associated and behavioral regulation. FMRI data showed biological underpinnings of ELS consequences. with a reduced volume of prefrontal cortex and that only activity in the amygdala differentiated Studies in animal models, especially rodents, hippocampus [15]. Remarkably, this study was the ELS-exposed children from the control group
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