Depressive symptoms, cortisol, and cognition during human aging: the role of negative aging perceptions.

Depressive symptoms and memory impairments are associated with heightened stress hormone levels during aging. A factor that is related to memory deficits during aging is internalized negative aging stereotypes; the idea people have about the process of aging. In this study, we assessed the associations between internalized negative aging stereotypes, depressive symptoms, subjective and objective memory assessments, and cortisol concentration among older adults. Forty older adults aged between 58 and 85 years (18 females and 22 males; mean age ± SD: 71.25 ± 8.80 years) were assessed in this study. Measures of internalized negative aging stereotypes, depressive symptoms, and both subjective and objective memory performance were assessed. Salivary samples were obtained for measurement of cortisol concentration. Stepwise linear regressions were executed in our main analyses. Internalized negative aging stereotypes were associated with increased depressive symptoms and subjective memory complaints. No significant differences were observed for objective memory performance, or cortisol concentration. Internalized negative aging stereotypes are associated with increased depressive symptomatology and subjective complaints of memory; however, they do not predict increased cortisol concentration nor objective memory performance during aging. These results indicate that the mechanism underlying the association between internalized negative aging stereotypes and cognitive impairments may not be related to dysregulations of cortisol secretion among older adults.

Influence of genetic polymorphisms in the apolipoprotein (APOE) and the butyrylcholinesterase (BCHE) gene on stress markers in older adults: a 3-year study.

The present study examined the influence of genetic polymorphisms in the apolipoprotein (APOE) and the butyrylcholinesterase (BCHE) gene on GC secretion, cognition and personality in 66 healthy older adults. These particular variables were chosen given that they have been shown to be associated with human stress (i.e.stress markers). Measures included basal serum GC levels and cognitive scores on declarative memory obtained annually over 3 years. Also, self-esteem, neuroticism and depression were evaluated. Results showed that participants with the APOE E4-BCHE K variant (E4-K group) present increased basal levels of GCs and poorer cognitive performance when compared to non-carriers of these variants. In addition, the E4-K group reported lower self-esteem and higher levels of depression. These findings may indicate a genotype effect on markers of stress and cognitive integrity years before symptoms of dementia are apparent.

Acute and long-term associations between ApoE genetic polymorphism, cortisol levels, and declarative memory performance in older adults.

CONTEXT: For the past two decades, researchers have shown that elevated levels of circulating stress hormones may negatively impact cognitive performance in older adults. As well, genetic polymorphism of the apolipoprotein E gene (APOE) has been found to contribute to impairment in cognitive performance in old age. To date, only one study has reported a relationship between APOE status and cortisol levels, however the relationship was only found to be significant in dementia patients, with a trend observed in healthy controls. OBJECTIVE: The goal of the present investigation was to examine the acute and long-term relationship between APOE status, cortisol secretion, and declarative memory performance in older adults. DESIGN: Two sample cohorts were assessed. In the first cohort, 24-h basal serum cortisol levels were obtained once a year over eight years to assess changes in basal cortisol levels over time. Declarative memory was also obtained in this group at three time-points over five years. In the second cohort, basal and stress-induced cortisol levels as well as basal declarative memory was tested. RESULTS: In the first cohort, E4 carriers were found to secrete higher serum cortisol levels than non-E4 carriers during the first 24-h visit (p=0.04) to the laboratory. However, this group difference did not remain over subsequent years. Furthermore, declarative memory performance over years did not significantly differ according to APOE status. In the second cohort, no significant group differences were found for basal or reactive cortisol levels (ps>0.05), and no group difference was found for acute declarative memory performance. CONCLUSION: The findings in this study suggest minimal to no significant effect of APOE status on cortisol secretion or declarative memory in non-demented older adults.

Impaired platelet [3H]paroxetine binding in female patients with borderline personality disorder.

RATIONALE: There have been few studies of platelet paroxetine binding in borderline personality disorder (BPD). OBJECTIVE: Our aim was to determine whether female BPD subjects show abnormalities in platelet paroxetine binding. METHODS: Twenty-one female BPD subjects and 16 age- and gender-matched normal control subjects were assessed using the following: (1) Diagnostic Interview for Borderlines, Revised, (2) Diagnostic Assessment for Personality Pathology: Brief Questionnaire, and (3) Barratt Impulsivity Scale. Platelets were collected and assayed for platelet paroxetine binding. RESULTS: Bmax was lower in the BPD group (p < 0.0001), but differences in Kd only reached a trend level. There were no associations with trait dimensions independent of diagnosis. CONCLUSIONS: Reduced platelet paroxetine binding in female BPD patients may reflect presynaptic serotonin dysfunction.

Secretion of melatonin in healthy elderly subjects: a longitudinal study.

UNLABELLED: We report on a 10-year longitudinal study on 24-h serum melatonin secretion (AUC) in healthy human subjects. Fifty women and 53 men (aged 42-83 yr) participated in the study initially. Of these, 18 women and 15 men were followed for 6 consecutive years. RESULTS: (a) Cross-sectional analysis (n = 103): A significant (R = -.49, P =.0001) decline in AUC melatonin with age was found in women, but not in men. (b) Longitudinal analysis (n = 33): Repeated-measure ANOVAs for women (n = 18): Time: linear F(1,17) = 5.14, P =.037. The AUC increased by about 40% over the six-year period. In men, there were no significant changes. CONCLUSION: In agreement with most cross-sectional studies, an inverse relationship was found between melatonin secretion and age. However, the longitudinal study showed an increase in melatonin secretion, indicating the presence of putative compensatory mechanisms during healthy aging. Changes in melatonin secretion were gender specific, occurring in women only.

Neurobiological correlates of diagnosis and underlying traits in patients with borderline personality disorder compared with normal controls.

The purpose of the study was to test the hypothesis that borderline personality disorder (BPD) and its underlying traits are associated with abnormalities in neurotransmitter systems. Subjects were 30 women with BPD and 22 normal controls, assessed using the Diagnostic Interview for Borderlines, revised, the Hamilton Depression Scale (HAM-A) and the Hamilton Anxiety Scale (HAM-A), the Diagnostic Assessment of Personality Pathology, the Buss-Durkee Guilt-Hostility Inventory, the Barratt Impulsivity Scale (BIS), and challenge tests to measure serotonergic, cholinergic and noradrenergic activity. Borderline subjects with high HAM-A and HAM-D scores showed a faster time to peak in prolactin response to meta-chlorphenylpiperazine (m-CPP) challenge. Borderline subjects with high BIS scores showed prolactin blunting. There were no differences in cortisol response to m-CPP, or on the cholinergic and noradrenergic challenges. The results suggest that impulsive traits in borderline patients are associated with abnormalities in serotonergic systems.

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.

The modulatory effects of corticosteroids on cognition: studies in young human populations.

In the present article, we report on two studies performed in young human populations which tested the cognitive impact of glucocorticoids (GC) in situations of decreased or increased ratio of mineralocorticoid (MR) and glucocorticoid (GR) receptor occupation. In the first study, we used a hormone replacement protocol in which we pharmacologically decreased cortisol levels by administration of metyrapone and then restored baseline cortisol levels by a subsequent hydrocortisone replacement treatment. Memory function was tested after each pharmacological manipulation. We observed that metyrapone treatment significantly impaired delayed recall, while hydrocortisone replacement restored performance at placebo level. In the second study, we took advantage of the circadian variation of circulating levels in cortisol and tested the impact of a bolus injection of 35 mg of hydrocortisone in the late afternoon, at a time of very low cortisol concentrations. In a previous study with young normal controls, we injected a similar dose of hydrocortisone in the morning, at the time of the circadian peak, and reported detrimental effects of GC on cognitive function. Here, when we injected a similar dose of hydrocortisone in the afternoon, at the time of the circadian trough, we observed positive effects of GC on memory function. The results of these two studies provide evidence that GC are necessary for learning and memory in human populations.