Sonia J. Lupien

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

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

Allostatic load biomarkers of chronic stress and impact on health and cognition

The allostatic load model expands the stress-disease literature by proposing a temporal cascade of multi-systemic physiological dysregulations that contribute to disease trajectories. By incorporating an allostatic load index representing neuroendocrine, immune, metabolic, and cardiovascular system functioning, numerous studies have demonstrated greater prediction of morbidity and mortality over and beyond traditional detection methods employed in biomedical practice. This article reviews theoretical and empirical work using the allostatic load model vis-à-vis the effects of chronic stress on physical and mental health. Specific risk and protective factors associated with increased allostatic load are elucidated and policies for promoting successful aging are proposed.

The acute effects of corticosteroids on cognition: integration of animal and human model studies

Cognitive deficits following acute administration of corticosteroids have been described in experimental animals and humans. In both populations, an inverted-U shape relationship has been reported between the dose of corticosteroids administered and the nature and extent of the cognitive deficits induced by corticosteroids. Further studies in animals have revealed a two-level recognition system for adrenal steroids, which was later more clearly resolved into two receptor types: Type I and Type II adrenal steroid receptors. The demonstration of an inverted-U shape relationship between corticosteroids and cognitive process leads to the question as to whether this relationship is generated via the two receptor types, exerting effects either via competing or opposing processes or via a more synergistic interaction. In this article, we review the effects of corticosteroids on animal and human cognition and propose a theoretical framework that leads to testable predictions regarding the acute effects of corticosteroids on cognitive function. We also discuss some methodological and experimental factors that might explain some discrepancies in data obtained from animals and humans. Furthermore, we suggest new experimental protocols for use in humans, based on animal literature, that could help resolve these discrepancies and assess more clearly the nature of the cognitive deficits induced by acute administration of corticosteroids.

Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans.

The effects of various doses (40 microg/kg/hr, 300 microg/kg/hr, 600 microg/kg/hr or placebo) of hydrocortisone on tasks assessing working and declarative memory function were measured in 4 groups of 10 young men. During the infusion, participants were given an item-recognition working memory task, a paired-associate declarative memory task, and a continuous performance task used to control possible concomitant effects of corticosteroids on vigilance. The results revealed significant acute effects of the highest dose of hydrocortisone on working memory function, without any significant effect on declarative memory function or arousal-vigilance performance. These results suggest that working memory is more sensitive than declarative memory to the acute elevations of corticosteroids, which could explain the detrimental effects of corticosteroids on acquisition and consolidation of information, as reported in the literature.

Child’s stress hormone levels correlate with mother’s socioeconomic status and depressive state

BACKGROUND Individuals with lower socioeconomic status report greater exposure to stressful life events and a greater impact of these events on their lives than individuals with higher socioeconomic status, and this relationship between socioeconomic status and health begins at the earliest stages of life. To extend on these results, we performed a psychoneuroendocrine study of 217 children and 139 mothers. METHODS Salivary cortisol levels and cognitive function were assessed in children, and a semistructured phone interview measuring symptoms of stress and depression was conducted with their mothers. RESULTS Children with low socioeconomic status present significantly higher salivary cortisol levels than children with high socioeconomic status, and this socioeconomic status effect emerges as early as age 6. We also report that a childs cortisol level is significantly correlated with his or her mothers extent of depressive symptomatology. CONCLUSIONS These results offer a neurobiological determinant to the well-known association between socioeconomic status and health that begins early in life.

Can poverty get under your skin? Basal cortisol levels and cognitive function in children from low and high socioeconomic status

It is well known that individuals from more advantaged social classes enjoy better mental and physical health than do individuals within lower classes. Various mechanisms have been evoked to explain the association between socioeconomic status (SES) and health. One mechanism that has received particular attention in recent years is stress. It has been shown that individuals lower in SES report greater exposure to stressful life events and a greater impact of these events on their life than individuals higher in SES. In order to measure whether the development of the relationship between SES and mental health is sustained by exposure to high levels of glucocorticoids, we measured morning salivary cortisol levels as well as cognitive function (memory, attention, and language) in 307 children (from 6 to 16 years of age) from low versus high SES in the Montreal area in Canada. The results revealed that low SES children from 6 to 10 years old present significantly higher salivary cortisol levels when compared to children from high SES. This difference disappears at the time of school transition, and no SES differences are observed in salivary cortisol levels during high school. However, children from low and high SES do not differ with regard to memory or to attentional and linguistic functions. Also, mothers of low SES children reported higher feelings of depression and more unhealthy behaviors, while mothers of high SES children reported higher stress related to work or family transitions. Altogether, these results show that low SES in young children is related to increased cortisol secretion, although the impact of SES on cortisol secretion is absent after transition to high school. These data are interpreted within the context of the equalization process of class patterning. Four social explanatory factors are suggested to explain the disappearance of SES differences in basal cortisol levels after school transition, taking into account the influence of family environment on the childs secretion of stress hormones.

Stress hormones and human memory function across the lifespan.

In this paper, we summarize the data obtained in our laboratory showing the effects of glucocorticoids on human cognitive function in older adults, young adults and children. We first present data obtained in the aged human population which showed that long-term exposure to high endogenous levels of glucocorticoids is associated with both memory impairments and a 14% smaller volume of the hippocampus. We then report on studies showing that in older adults with moderate levels of glucocorticoids, memory performance can be acutely modulated by pharmacological manipulations of glucocorticoids. In young adults, we present data obtained in our laboratory showing that cognitive processing sustained by the frontal lobes is also sensitive to acute increases of glucocorticoids. We also summarize studies showing that just as in older adults, memory performance in young adults can be acutely modulated by pharmacological manipulations of glucocorticoids. We then present a study in which we showed a differential involvement of adrenergic and glucocorticoid hormones for short- and long-term memory of neutral and emotional information. In the last section of the paper, we present data obtained in a population of young children and teenagers from low and high socioeconomic status (SES), where we showed that children from low SES present significantly higher levels of basal cortisol when compared to children from high SES. We then present new data obtained in this population showing that children and teenagers from low and high SES do not process the plausibility of positive and negative attributes in the same way. Children from low SES tended to process positive and negative attributes on a more negative note than children from high SES, and this type of processing was significantly related to basal cortisol at age 10, 12 and 14. Altogether, the results of these studies show that both bottom-up (effects of glucocorticoids on cognitive function), and top-down (effects of cognitive processing on glucocorticoid secretion) effects exist in the human population.

Stress, memory, and the hippocampus: can't live with it, can't live without it

Since the 1968s discovery of receptors for stress hormones (corticosteroids) in the rodent hippocampus, a tremendous amount of data has been gathered on the specific and somewhat isolated role of the hippocampus in stress reactivity. The hippocampal sensitivity to stress has also been extended in order to explain the negative impact of stress and related stress hormones on animal and human cognitive function. As a consequence, a majority of studies now uses the stress-hippocampus link as a working hypothesis in setting up experimental protocols. However, in the last decade, new data were gathered showing that stress impacts on many cortical and subcortical brain structures other than the hippocampus. The goal of this paper is to summarize the four major arguments previously used in order to confirm the stress-hippocampus link, and to describe new data showing the implication of other brain regions for each of these previously used arguments. The conclusion of this analysis will be that scientists should gain from extending the impact of stress hormones to other brain regions, since hormonal functions on the brain are best explained by their modulatory role on various brain structures, rather than by their unique impact on one particular brain region.

Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening.

Objective There is evidence that clinical depression and negative mood are associated with elevated basal cortisol levels. Recently, measuring the cortisol response during the first hour in the morning with strict reference to the time of awakening was established as a reliable marker of individual adrenocortical activity. In studies using this marker, a relationship with self-reported stress levels and psychosomatic symptoms has been found. The goal of the present study was to investigate the association of self-reported depressive symptomatology with early morning free cortisol levels and their relationship to measures of stress. Methods We assessed the severity of depressive symptoms using the Hamilton Depression Inventory and chronic and acute stress perception in 40 healthy young men. Once a week, for 4 consecutive weeks, subjects provided saliva samples collected at 0, 30, and 60 minutes after awakening. Results Higher levels of depressive symptomatology were associated with a greater cortisol response after awakening. This association seemed to be stronger when only subjects in the nonclinical range of depression were included. Furthermore, cortisol levels and depressive symptomatology were significantly positively correlated with measures of chronic and acute stress perception. Conclusions The present study extends earlier findings of hypothalamus-pituitary-adrenal axis hyperactivity in clinical depression to healthy young men with mild levels of depressive symptomatology. Measuring the cortisol response to awakening is proposed as an economical alternative to traditional approaches for determining basal hypothalamus-pituitary-adrenal axis activity. Associations between depressive symptomatology and chronic stress, as well as implications for future studies, are discussed.

Deactivation of the Limbic System During Acute Psychosocial Stress: Evidence from Positron Emission Tomography and Functional Magnetic Resonance Imaging Studies

BACKGROUND Stress-induced metabolic changes can have detrimental health effects. Newly developed paradigms to investigate stress in neuroimaging environments allow the assessment of brain activation changes in association with the perception of and the metabolic response to stress. METHODS We exposed human subjects to a psychosocial stressor in one positron emission tomography (n = 10) and one functional magnetic resonance imaging (fMRI; n = 40) experiment. RESULTS We observed a profound deactivation of limbic system components including hippocampus, hypothalamus, medio-orbitofrontal cortex and anterior cingulate cortex in subjects who reacted to the stressor with a significant increase of the endocrine stress marker cortisol. Further, in the fMRI study, the degree of deactivation in the hippocampus was correlated with the release of cortisol in response to the stress task. CONCLUSIONS The observed deactivation of limbic system structures suggests elevated activation at rest and during nonstressful situations. A model is proposed where the observed reduction in limbic system activity is essential for the initiation of the stress response.