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Biomedical subjects

S J Lupien

Publications and source records attributed to S J Lupien.

17 recordsLinked to original sources
PubMed2006

Hippocampal volume is as variable in young as in older adults: implications for the notion of hippocampal atrophy in humans.

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Adolescent↗
PubMed2006

Do corticosteroids damage the brain?

Corticosteroids are an essential component of the body's homeostatic system. In common with other such systems, this implies that corticosteroid levels in blood and, more importantly, in the tissues remain within an optimal range. It also implies that this range may vary according to circumstance. Lack of corticosteroids, such as untreated Addison's disease, can be fatal in humans. In this review, we are principally concerned with excess or disturbed patterns of circulating corticosteroids in the longer or shorter term, and the effects they have on the brain.

Adrenal Cortex Hormones↗
PubMed2006

Multiparity reveals the blunting effect of breastfeeding on physiological reactivity to psychological stress.

Rat studies show that hypothalamic-pituitary-adrenal (HPA) responsiveness to physical and emotional stressors is attenuated during lactation, although situations evoking pup endangerment can supersede this phenomenon. In the human population, blunted cortisol responses are seen in primiparous breastfeeding compared to bottlefeeding mothers following physical stress, but not after psychosocial stress. It is currently unknown whether stressor salience (child-related versus nonrelated stressor) has a differential effect on cortisol reactivity as a function of infant feeding choice and whether HPA responses to stress could be modified by parity. We investigated the impact of infant feeding type and maternal parity on salivary cortisol and alpha-amylase response to stress in 5-20-week postpartum mothers using exposure to the Trier Social Stress Test (TSST) and to an emotional film evoking threats to a child. Analyses show that alpha-amylase responses were similar in all groups and for both types of stress, suggesting that sympathetic reactivity was independent of infant feeding type and parity. By contrast, cortisol response was affected by these variables. In primiparous mothers, cortisol reactivity to psychological stressors did not vary as a function of infant feeding type while, among multiparous mothers, breastfeeding was associated with reduced responsiveness to the TSST and child-related stressor. We speculate that changes in neural mechanisms occurring as a result of pregnancy and lactation and that modulate the HPA axis in women might be exacerbated with multiple repeats of the pregnancy/lactation period. This would serve to 'desensitise' stress circuits and reduce the overall stress-induced cortisol secretion after multiple births.

Adaptation, Physiological↗
PubMed2004

Successful ageing: from cell to self.

Many people see ageing as a time of cognitive and physical decline. For the past three decades, most scientists and the general public have accepted this negative age-stereotype as the norm, but fortunately this view is now challenged. New findings show that well-being and a positive view of ageing are major protective factors against the effects of age on the organism. These results challenge the scientific studies that place emphasis on the negative side of ageing. This ageism view has been observed in each sphere of science, from genetics to social sciences. Perspectives from each domain are described, and new integrative views of successful ageing are summarized.

Aging↗
PubMed2002

Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids.

In a previous longitudinal study of basal cortisol levels and cognitive function in humans, we showed that elderly humans with 4- to 7-yr cumulative exposure to high levels of cortisol present memory impairments, compared with elderly humans with moderate cortisol levels over years. Here, we measured whether memory performance in two groups of elderly humans separated on the basis of their cortisol history over a 5-yr period could be modulated by a hormone-replacement protocol in which we inhibited cortisol secretion by the administration of metyrapone and then restored baseline cortisol levels by infusion of hydrocortisone. We showed that in elderly subjects with a 5-yr history of moderate cortisol levels (n = 8), metyrapone treatment significantly impaired memory performance, a deficit that was reversed following hydrocortisone replacement. In the elderly subjects with a 5-yr history of high cortisol levels and current memory deficits (n = 9), metyrapone treatment did not have any significant effect on memory performance, but hydrocortisone treatment significantly decreased delayed memory. These results suggest that memory function in elderly humans can be intensely modulated by pharmacological manipulation of glucocorticoids, although the direction of these effects depends on the cortisol history of each individual.

Aged↗
PubMed2001

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.

Animals↗
PubMed2001

Circulating human corticotropin-releasing factor-binding protein levels following cortisol infusions.

Corticotropin-releasing factor-binding protein (CRF-BP) is a 37 kDa protein present in the brain and plasma and is known to regulate the actions of CRF. It has been demonstrated that CRF-BP in the brain and the pituitary appears to be positively regulated by glucocorticoids. In this study, the effect of various doses of hydrocortisone infusions on plasma CRF-BP levels was assessed. Four groups of 10 age-matched males received a 100 min infusion of either placebo (saline), 40 microg/kg/h, 300 microg/kg/h or 600 microg/kg/h hydrocortisone. CRF-BP levels were measured via a LIRMA. In addition, levels of plasma ACTH and cortisol were measured by standard radioimmunoassay. As expected, plasma cortisol levels increased and plasma ACTH levels were suppressed following the infusion. When expressed as proportion of pre-infusion baseine, no significant changes in plasma CRF-BP levels were observed following the infusion for all hydrocortisone groups relative to the control group. However, a significant time-averaged positive correlation was found between CRF-BP and cortisol levels at low to moderate, but not high, cortisol levels. The data obtained in this study indicate that CRF binding protein levels within the time course examined may slightly appear to be affected in the peripheral circulation in response to pronounced, sustained hypercortisolemia.

Adult↗
PubMed2001

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 child's secretion of stress hormones.

Adolescent↗
PubMed2000

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 child's cortisol level is significantly correlated with his or her mother's 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.

Age Factors↗
PubMed1999

Support for a bimodal role for type II adrenal steroid receptors in spatial memory.

We investigated the effects of acute adrenal steroid treatment on spatial memory using the Y-maze and employing adrenal steroid receptor antagonists and agonists. For receptor activation, adrenalectomized rats were injected 2 h prior to their first Y-maze trial with sesame oil (adrenalectomy or SHAM), stress levels of corticosterone, a Type I receptor agonist (aldosterone), or a Type II receptor agonist (RU362). For receptor inactivation, unoperated rats were injected with a Type I receptor antagonist (RU318), a Type II receptor antagonist (RU555), sesame oil, or not injected at all. The findings indicated that spatial memory was impaired when the Type II receptors were blocked (RU555) or highly occupied (corticosterone or RU362) and normal for the other treatment conditions. These data suggest that the Type II receptors may be responsible for the inverted U-shaped relationship between spatial memory and corticosterone levels reported by others.

Adrenalectomy↗
PubMed1999

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.

Adrenocorticotropic Hormone↗
PubMed1999

Increased cortisol levels and impaired cognition in human aging: implication for depression and dementia in later life.

Perhaps the most prominent feature of human aging is the variability in decline of intellectual processes. Although many research avenues have been used to study the origin of such an increased variability with aging, new studies show that some biological factors may be associated with normal and pathological cognitive aging. One biological parameter that came under scrutiny in the past few years is the hypothalamic-pituitary-adrenal (HPA) axis, an endocrine closed-loop system controlling the secretion of stress hormones (glucocorticoids). In this review, we summarize data obtained in both animals and humans suggesting that cumulative exposure to high levels of glucocorticoids can be particularly detrimental for the aged hippocampus, a brain structure involved in learning and memory in both animals and humans. We then analyze the implication of these data for the study of dementia and depression in later life, two disorders characterized by increased glucocorticoid secretion in a significant proportion of patients. Finally, we suggest various factors that could explain the development of glucocorticoid hypersecretion in later life.

Aging↗
PubMed1998

Cortisol levels during human aging predict hippocampal atrophy and memory deficits.

Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans.

Aged↗
PubMed1997

The effects of type I and type II corticosteroid receptor agonists on exploratory behavior and spatial memory in the Y-maze.

We investigated the effects of two adrenal steroid agonists on adrenalectomized (ADX) rats' performance on the Y-maze. The Y-maze was chosen because memory can be assessed quickly and because it is sensitive to various parameters of exploratory behavior and spatial memory performance. Four days after surgery, ADX rats were injected with aldosterone (ALDO, a selective Type I receptor agonist), RU362 (a selective Type II receptor agonist) or sesame vehicle at three different time points (120 min prior to Trial 1, immediately after Trial 1 or 120 min after Trial 1). SHAM-operated rats injected with vehicle were also tested. The results indicate that vehicle-treated ADX rats were impaired on spatial recognition memory compared to SHAM rats. Treatment with ALDO restored spatial recognition memory performance of ADX rats to a level comparable to SHAM-treated rats by acting on acquisition and consolidation, whereas treatment with RU362 did not change the poor spatial recognition memory performance of ADX rats. Discrimination memory was improved only when either agonist was injected prior to the first trial, strongly suggesting a non-selective effect of corticosteroids on discrimination memory such as increasing arousal. A detailed analysis of exploratory behavior showed that both the ALDO- and RU362-treated rats explored the Y-maze more than the ADX and SHAM groups at all periods of the experiment. These results show that the non-specific increase in exploratory behavior induced by replacing corticosteroids targeted at Type I and Type II receptors was used differentially with the ALDO-treated rats learning and consolidating spatial information better than the RU362-treated rats. These data are discussed along with other evidence to suggest that Type II receptors may require the simultaneous occupancy of Type I receptors to affect learning and memory processes.

Adrenalectomy↗
PubMed1997

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.

Adrenal Cortex Hormones↗
PubMed1997

Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity.

A group of 14 healthy elderly subjects was submitted to a nonstressful (attentional task) and a stressful (public speaking task) condition. Declarative (conscious recollection of learned information) and nondeclarative (retrieved information without conscious or explicit access) memory as well as salivary cortisol levels were measured before and after each condition. The results showed that the stressful condition significantly decreased declarative memory performance, whereas the nonstressful condition did not. Nondeclarative memory performance was not affected by either condition. Further analyses separating the subjects into responders and nonresponders in terms of stress-induced cortisol changes revealed a very different pattern of cortisol secretion and declarative memory performance in both populations. We showed that the responders presented increased cortisol levels 60 min before the actual stressor, whereas the nonresponders presented increased cortisol levels 25 min before the actual stressor. Although the responders did not differ from the nonresponders in declarative memory performance before and after the nonstressful condition, they presented a lower declarative memory performance when measured before and after the stressful condition. The early increase in cortisol levels observed in the responder group suggests that the anticipation of the stress, rather than the actual stressor per se, may have played a more significant role in the stress-induced declarative memory deficits observed in this subgroup. Together, these results show that the cortisol response to anticipation of stress and/or to stress in the elderly specifically affects those memory functions that are dependent on hippocampal activity. They also suggest that an altered cortisol responsivity to acute and/or chronic stress, with its detrimental effects on memory, could be an important factor explaining the genesis of memory deficits in aged populations.

Aged↗