Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory

McClelland, Shawn; Kőrösi, Anikó; Cope, Jessica Lack; Ivy, Autumn S; Baram, Tallie Z.

doi:10.1016/j.nlm.2011.02.008

Cited by 99 publications

(94 citation statements)

References 135 publications

(223 reference statements)

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“…For example, the reduced size of the hippocampus and associated behavioural impairments in the infant that result from intrauterine growth restriction may reflect maternal corticosteroid hormone exposure, hypoxaemia, and micronutrient deficiency (Lodygensky et al 2008). In addition, McClelland et al (2011) have described the epigenetic mediation of the long-lasting effects of early experience on learning and memory abilities.…”

Section: Adhdmentioning

confidence: 99%

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Oades

2011

ADHD Atten Def Hyp Disord

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Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance. Serum was taken from 35 children with DSM-IV ADHD (14 on medication) and 21 typically developing controls to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-α and IFN-γ) and 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-hydroxyindole acetic acid [5-HIAA]). The mothers received a 124-item questionnaire on features surrounding the pregnancy. (1) For children with ADHD, a shorter pregnancy and smaller birth weight were associated statistically with increased 3HK and IFN-γ and for obstetric problems with decreased TNF-α levels. (2) Maternal smoking related to decreasing kynurenine and increasing 3HK and S100B levels in ADHD children. Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children. (3) The taking of supplements often related to decreasing TNF-α, increasing IL-10 and lower 5-HIAA levels in the ADHD children. Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively. (4) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. Unexpectedly, more child care (seafood and time together) in ADHD than healthy families was implicated by lower tryptophan levels and an altered balance of pro-inflammatory cytokines. Across measures control families generally showed either non-significant associations or the opposite to those of the ADHD group. In ADHD children more than controls, the balance of potentially toxic or protective kynurenine metabolites and of pro- over anti-inflammatory cytokines may reflect the perinatal experience associated with stress, but not with maternal illness.

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Section: Adhdmentioning

confidence: 99%

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Oades

2011

ADHD Atten Def Hyp Disord

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“…Providing infants with a caring and stimulating environment is generally considered ideal for fostering cognitive development (10). One reason is that infants growing up in such an environment are protected from frequent stress exposure.…”

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confidence: 99%

Stress impairs cognitive flexibility in infants

Seehagen

Schneider

Rudolph

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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In human adults, learning and memory under acute stress are characterized by an increased use of rigid habitual response strategies at the cost of flexible cognitive strategies. The immediate effects of stress on cognitive functioning early in life are not well understood. Here we show experimentally that acute stress leads human infants to perform habitual behavior rigidly. We found that 15-mo-old infants exposed to stress thereafter kept performing a previously effective action, even after the action suddenly became ineffective. Infants in a no-stress control group flexibly adjusted their behavior by disengaging from the newly ineffective action in favor of exploring an alternative action. This finding demonstrates that stress impairs infants' ability to adjust their behavior to changing circumstances.S tress is pervasive in modern society. It is by definition aversive, but how potentially stressful experiences affect a person depends on a variety of factors, such as the person's age, developmental history, temperament, and the type of stressor (1, 2). Thus, the very same set of challenges that inspires peak performance in some people might leave others drained. In addition to its relevance for mental and physical well-being, stress alters the way human adults think. Learning and memory under acute stress are characterized by increased use of rigid habitual response strategies at the cost of flexible cognitive strategies (3-5). For example, stressed adults continue to select a particular beverage even after they have become satiated with its flavor, whereas satiated nonstressed adults select a new beverage (4). This shift from hippocampus-dependent to dorsal striatum-dependent memory is mediated by an increase of the stress hormone cortisol (6-8).In the first years of life, core characteristics of the human brain are its rapid development and high plasticity (9). Providing infants with a caring and stimulating environment is generally considered ideal for fostering cognitive development (10). One reason is that infants growing up in such an environment are protected from frequent stress exposure. However, the immediate consequences of stress exposure on infant cognition are not well understood. In a number of previous studies, children between 1 and 5 y of age were unlikely to show a physiological response (i.e., an increase in cortisol levels) to mildly threatening situations, such as being in an unfamiliar environment or being approached by an unfamiliar person (11,12). This human equivalent to the so-called hyporesponsive phase reported in rodents is thought to protect the developing brain from potentially harmful effects of acute stress (13). However, this idea is somewhat at odds with a minority of studies in which stress induction did lead to increased cortisol levels in young children (14,15). Furthermore, chronic stress exposure early in life is associated with long-term impairments in cognitive functioning (16). Thus, even if a cortisol response can be difficult to elicit, it seems unlikely that early...

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“…The primary aim of the present study, therefore, was to construct an ontogenetic timeline of memory in mice using contextual fear conditioning, a well-characterized aversive learning paradigm (Anagnostaras et al 2001;Rudy et al 2004). Furthermore, although maladaptive early life experience is often shown to produce cognitive impairments that are evident long after the initial trauma (Sullivan et al 2006;McClelland et al 2011), less research has focused on whether early adversity delays the initial onset of learning and memory in young animals. Thus, our second aim was to determine whether an ontogenetic timeline of contextual fear memory could be used to detect developmental delays resulting from one type of adverse early life experience-fetal exposure to alcohol.…”

mentioning

confidence: 99%

Ontogeny of contextual fear memory formation, specificity, and persistence in mice

et al. 2012

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Pinpointing the precise age when young animals begin to form memories of aversive events is valuable for understanding the onset of anxiety and mood disorders and for detecting early cognitive impairment in models of childhood-onset disorders. Although these disorders are most commonly modeled in mice, we know little regarding the development of learning and memory in this species because most previous studies have been restricted to rats. Therefore, in the present study, we constructed an ontogenetic timeline of contextual fear memory ranging from infancy to adulthood in mice. We found that the ability of mice to form long-term context-shock associations emerged 13 -14 d of age, which is several days earlier than previously reported for rats. Although the ability to form contextual fear memories remained stable from infancy into adulthood, infant mice had shorter-lasting memories than adolescent and adult mice. Furthermore, we found that mice subjected to fetal alcohol exposure showed a delay in the developmental emergence of contextual fear memory, illustrating the utility of this ontogenetic approach in detecting developmental delays in cognitive function stemming from maladaptive early life experience.

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Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory

Cited by 99 publications

References 135 publications

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Stress impairs cognitive flexibility in infants

Ontogeny of contextual fear memory formation, specificity, and persistence in mice

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