New insights into early-life stress and behavioral outcomes

doi:10.1016/j.cobeha.2016.12.012

Current Opinion in Behavioral Sciences

Volume 14, April 2017, Pages 133-139

https://doi.org/10.1016/j.cobeha.2016.12.012 Get rights and content

Highlights

•
Early-life stress is linked with vulnerability to cognitive and emotional disorders.
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Naturalistic animal models of early-life stress are critical to identify mechanisms.
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Recent studies report outcomes ranging from hippocampus-dependent memory deficits to emotional consequences such as anhedonia and depression.

Adverse early-life experiences, including various forms of early-life stress, have consistently been linked with vulnerability to cognitive and emotional disorders later in life. Understanding the mechanisms underlying the enduring consequences of early-life stress is an active area of research, because this knowledge is critical for developing potential interventions. Animal models of early-life stress typically rely on manipulating maternal/parental presence and care, because these are the major sources of early-life experiences in humans. Diverse models have been created, and have resulted in a wealth of behavioral outcomes. Here we focus on recent findings highlighting early-life stress-induced behavioral disturbances, ranging from hippocampus-dependent memory deficits to problems with experiencing pleasure (anhedonia). The use of naturalistic animal models of chronic early-life stress provides insight into the spectrum of cognitive and emotional outcomes and enables probing the underlying mechanisms using molecular-, cellular-, and network-level approaches.

Introduction

Mental illnesses and cognitive disorders commence predominantly early in life [1, 2], suggesting the need to explore events early on that predispose and contribute to disease onset. Epidemiological data indicate that various forms of early-life stress in humans can have life-long impacts, ranging from memory deficits and poor executive functioning [3, 4, 5] to more explicitly stress-related disorders such as depression, anxiety, and post-traumatic stress disorders [6, 7, 8, 9, 10, 11]. Adverse early-life conditions, including poverty, loss of a parent, substance abuse by the mother or maternal depression, are consistently associated with vulnerability to various psychopathologies later in life [12, 13, 14, 15]. Understanding the mechanisms for the enduring consequences of early-life stress on brain function has been an active area of neuroscience research, as this knowledge is critical for identifying clinically plausible therapeutic strategies. This review will focus on the behavioral outcomes of early-life stress, with a particular emphasis on new findings emerging within the past few years, and conclude with a unifying theory for how these profound changes may occur.

Section snippets

What is early-life stress?

The type and severity of the perturbations that cause early-life stress seem to govern its consequences. In humans, chronic early-life stress has both physical and emotional components, but the emotional aspects are dominant. Among the most influential studies of the effects of early-life stress are those of institutionally raised children, where chronic impoverished care was associated with cognitive and emotional problems [4, 16]. Notably, the associated consequences were partially reversed

Modeling early-life stress

In mammals, including humans, monkeys and rodents, maternal input has perhaps the most significant influence on the environment experienced during development [20, 22, 23, 24, 25]. Thus, most animal models of early-life stress have manipulated maternal interaction, disrupting either the quantity or quality of maternal care early in life (see Refs. [26•, 27•] for recent reviews). Non-human primates, whose brains and sociality most closely resemble those of humans, have provided useful insights

Modeling the behavioral outcomes of early-life stress

The specific later-life consequences of early-life stress in humans are modeled in rodents using standardized cognitive and emotional tests that have been designed to optimize translation to the human condition. For example, rodent tests of depressive-like behavior, such as the forced-swim test (FST), have been validated to show improvement with human antidepressants [64]. Human cognitive function, though much more complex than in rodents, is subserved by areas of the brain that are homologous

A spectrum of cognitive consequences of chronic early-life stress

Diverse cognitive effects of early-life stress have been reported. For example, MS stress on postnatal day 9 has led to improved memory in the active avoidance test [70], whereas the same manipulation on postnatal day 4 has led to impaired memory in the same test [70]. This latter finding is more in line with the majority of the MS literature, which includes reports of impairments in the Morris Water maze test and OR [40, 71]. There may be several possible bases for these divergent outcomes,

Recent findings for emotional consequences of chronic early-life stress

A variety of emotional problems, based on rodent tasks considered indicative of depression or anxiety, have been reported after early-life stress [26•, 74, 75, 76]. More recently, anhedonia, a reduced capacity to experience pleasure which commonly heralds depression or schizophrenia in humans [77], has been identified following early-life stress. Already during adolescence, anhedonia, apparent both as a significant reduction in sucrose preference and a reduction of peer-play, was found in LBN

Conclusions

Stress has profound effects on the brain, manifesting as altered behavioral outcomes. This is especially true when the stress occurs during vulnerable developmental periods. Brain maturation involves multiple dynamic processes that are regulated both by genetic factors and environmental input [87, 88, 89, 90]. Many of these processes continue during postnatal life. Although it is impossible to directly compare rodent and human brain development and their trajectories, there is excellent

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Conflict of interest statement

The authors declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Acknowledgements

This work was supported by the National Institutes of Health [grant numbers R01MH073136, R01S028912, P50MH096889] and the George E. Hewitt Foundation for Medical Research.

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View full text

New insights into early-life stress and behavioral outcomes

Highlights

Introduction

Section snippets

What is early-life stress?

Modeling early-life stress

Modeling the behavioral outcomes of early-life stress

A spectrum of cognitive consequences of chronic early-life stress

Recent findings for emotional consequences of chronic early-life stress

Conclusions

References and recommended reading

Conflict of interest statement

Acknowledgements

Child Adolesc Psychiatr Clin N Am

Psychoneuroendocrinology

Biol Psychiatry

Psychoneuroendocrinology

Trends Cogn Sci

Rev Neurosci

Neurosci Biobehav Rev

Physiol Behav

Hippocampus

Pharmacol Biochem Behav

Trauma Violence Abuse

Hippocampus

Endocrinology

J Neurosci

Pain

J Neurosci

Environ Health Perspect

Neuropsychopharmacology

Ment Retard Dev Disabil Res Rev

Neurosci Biobehav Rev

Neuropharmacology

Proc Natl Acad Sci U S A

J Comp Neurol

Science

Am J Psychiatry

N Engl J Med

J Neurosci

Nat Rev Neurosci

Prevalence and treatment of mental disorders, 1990 to 2003

N Engl J Med

Childhood socioeconomic position and cognitive function in adulthood

Int J Epidemiol

Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project

Science

Chronic distress and incidence of mild cognitive impairment

Neurology

Impact of child sexual abuse: a review of the research

Psychol Bull

An ecological-transactional analysis of children and contexts: the longitudinal interplay among child maltreatment, community violence, and children’s symptomatology

Dev Psychopathol

Childhood abuse and lifetime psychopathology in a community sample

Am J Psychiatry

A meta-analysis of the published research on the effects of child sexual abuse

J Psychol

Effects of stress throughout the lifespan on the brain, behaviour and cognition

Nat Rev Neurosci

Risky families: family social environments and the mental and physical health of offspring

Psychol Bull

Attachment and the regulation of the right brain

Attach Hum Dev

Salivary cortisol levels in children adopted from Romanian orphanages

Dev Psychopathol

V. The neurobiological toll of early human deprivation

Monogr Soc Res Child Dev

The developmental effects of early life stress: an overview of current theoretical frameworks

Curr Dir Psychol Sci

Research into the origins of delinquent behaviour

Br Med J

Fragmentation and unpredictability of early-life experience in mental disorders

Am J Psychiatry

Mother-infant separation in monkeys

J Child Psychol Psychiatry

Early life trauma and attachment: immediate and enduring effects on neurobehavioral and stress axis development

Front Endocrinol

Early-life experience, epigenetics, and the developing brain

Neuropsychopharmacology

Naturalistic rodent models of chronic early-life stress