J. Herbert

Endogenous steroids and financial risk taking on a London trading floor

Little is known about the role of the endocrine system in financial risk taking. Here, we report the findings of a study in which we sampled, under real working conditions, endogenous steroids from a group of male traders in the City of London. We found that a traders morning testosterone level predicts his days profitability. We also found that a traders cortisol rises with both the variance of his trading results and the volatility of the market. Our results suggest that higher testosterone may contribute to economic return, whereas cortisol is increased by risk. Our results point to a further possibility: testosterone and cortisol are known to have cognitive and behavioral effects, so if the acutely elevated steroids we observed were to persist or increase as volatility rises, they may shift risk preferences and even affect a traders ability to engage in rational choice.

Regional changes in c-fos expression in the basal forebrain and brainstem during adaptation to repeated stress: Correlations with cardiovascular, hypothermic and endocrine responses

Acute stress is known to evoke a discrete pattern of c-fos expression in the brain. The work reported here shows that this pattern is modified in regionally specific ways following repeated stress, and that this can be correlated with changes in telemetered heart rate, core temperature and corticosterone output that occur during adaptation. Intact male rats were restrained for 60 min daily for one or 10 days. Stress-induced tachycardia was maximal 10 min following the onset of restraint, and decreased thereafter. The peak value was not altered by repeated restraint, but levels fell towards baseline values more rapidly with increasing bouts of stress. Core temperature showed marked reduction during the first 10 min of the initial stress, followed by a minor (and not very consistent) overshoot during the remainder of the stress period. In contrast to heart rate, stress-induced hypothermia did not alter during repeated restraint. Corticosterone was raised dramatically immediately following the first 60-min session of restraint, and this was attenuated by repeated stress. Sixty minutes after the end of the first stress session, there was pronounced c-fos expression in the lateral septum, lateral preoptic area, lateral hypothalamic area, all divisions of the hypothalamic paraventricular nucleus, the medial (but not central) amygdala, the locus ceruleus and a brainstem structure (thought to be Barringtons nucleus), compared to rats transferred to the testing room but not restrained. Sixty minutes after the 10th stress session, c-fos expression was markedly decreased in some of these areas compared with the pattern observed after the first stress, especially in the paraventricular nucleus (dorsal and medial parvicellular regions) and in medial amygdala. However, all other areas measured demonstrated a sustained response even after repeated stress. There were no significant differences in c-fos expression in rats repeatedly transferred to the testing room (but not stressed) compared to singly transferred counterparts. These results show that both neuronal and physiological responses adapt to a repeated stress, but that in both cases this has highly specific components. It seems likely that adaptive changes in c-fos expression are associated with those in some features of autonomic and endocrine reactions. It is noteworthy that there is evidence that the lateral septum, in which c-fos expression did not diminish after repeated stress, may be involved in temperature control, whereas the paraventricular nucleus, in which c-fos did alter, has been linked with both cardiac and corticoid regulation.

Do Corticosteroids Damage the Brain

Corticosteroids are an essential component of the bodys 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 Addisons 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.

Exposure to postnatal depression predicts elevated cortisol in adolescent offspring

BACKGROUND Animal research shows that early adverse experience results in altered glucocorticoid levels in adulthood, either raised basal levels or accentuated responses to stress. If a similar phenomenon operates in humans, this suggests a biological mechanism whereby early adversity might transmit risk for major depression, glucocorticoid elevations being associated with the development of this disorder. METHODS We measured salivary cortisol at 8:00 am and 8:00 pm over 10 days in 13-year-old adolescents who had (n = 48) or had not (n = 39) been exposed to postnatal maternal depression. RESULTS Maternal postnatal depression was associated with higher, more variable morning cortisol in offspring, a pattern previously found to predict major depression. CONCLUSIONS Early adverse experiences might alter later steroid levels in humans. Because maternal depression confers added risk for depression to children, these alterations might provide a link between early events and later psychopathology.

Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression

Treating adult male rats with subcutaneous pellets of dehydroepiandrosterone (DHEA) increased the number of newly formed cells in the dentate gyrus of the hippocampus, and also antagonized the suppressive of corticosterone (40 mg/kg body weight daily for 5 days). Neither pregnenolone (40 mg/kg/day), a precursor of DHEA, nor androstenediol (40 mg/kg/day), a major metabolite, replicated the effect of DHEA (40 mg/kg/day). Corticosterone reduced the number of cells labelled with a marker for neurons (NeuN) following a 28‐day survival period, and this was also prevented by DHEA. DHEA by itself increased the number of newly formed neurons, but only if treatment was continued throughout the period of survival. Subcutaneous DHEA pellets stimulated neurogenesis in a small number of older rats (≈ 12 months old). These results show that DHEA, a steroid prominent in the blood and cerebral environment of humans, but which decreases markedly with age and during major depressive disorder, regulates neurogenesis in the hippocampus and modulates the inhibitory effect of increased corticoids on both the formation of new neurons and their survival.

Adrenal secretion during major depression in 8- to 16-year-olds, I. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation.

The association between basal cortisol, dehydroepiandrosterone (DHEA), its sulphate (DHEAS) and major depression was investigated in 8- to 16-year-olds. Eighty-two subjects with major depression, 25 non-depressed psychiatric cases and 40 community controls were systematically assessed for current mental state and hormone levels at 08.00, 12.00 and 20.00 h, assayed from salivary samples collected over a 48 h period. The average mean of the two time points was compared between the three groups. Evening cortisol hypersecretion and morning DHEA hyposecretion were significantly, and independently, associated with major depression. High evening cortisol (> 0.594 ng/mL) and low morning DHEA (< 0.200 ng/mL) identified subgroups of depressives with different types of adrenal hormone dysregulation. The association between high evening cortisol or low morning DHEA and MDD was not affected by either age or gender.

Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats

Intraspecific confrontation between male rats represents a biologically relevant form of social stress. C‐fos expression has been used to map the pattern of neural activation following either a single (acute) or repeated (10 times) exposure of an intruder male to a larger male in the latter’s home cage. These conditions induce high levels of aggressive interaction.

Dehydroepiandrosterone antagonizes the neurotoxic effects of corticosterone and translocation of stress-activated protein kinase 3 in hippocampal primary cultures

Glucocorticoids are toxic to hippocampal neurons. We report here that the steroid dehydroepiandrosterone protects neurons of primary hippocampal cultures against the toxic effects of corticosterone. Corticosterone (20-500 nM) added for 24h to primary cultures of embryonic day 18 rat hippocampus resulted in significant neurotoxicity. Dissociated cells were grown for at least 10 days, initially in serum-containing medium, but serum was removed before adding steroids for 24 h. Neurotoxicity was measured by counting the number of cells stained either for beta-tubulin III or glial fibrillary acidic protein. Corticosterone-induced toxicity was prevented by co-treatment of the cultures with dehydroepiandrosterone (20-500 nM). Dehydroepiandrosterone on its own had little effect, though the highest concentration used (500 nM) was mildly toxic. Immunohistochemical studies on the nuclear translocation of a range of stress-activated protein kinases showed that stress-activated protein kinases 1, 2, 3 and 4 were all translocated by 10 min exposure to corticosterone (100 nM). Dehydroepiandrosterone (100 nM) attenuated the translocation of stress-activated protein kinase 3, but not the others. These experiments show that dehydroepiandrosterone has potent anti-glucocorticoid actions on the brain, and can protect hippocampal neurons from glucocorticoid-induced neurotoxicity. This protective action may involve stress-activated protein kinase 3-related intracellular pathways, though direct evidence for this has still to be obtained.

Salivary cortisol and dehydroepiandrosterone in relation to puberty and gender

This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their relation to gender and pubertal development, in healthy children and adolescents. Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years. Subjects provided morning (08:00 h) and evening (20:00 h) saliva samples over four consecutive days. Pubertal stage was assessed using Tanner stage sketches, and subjects were grouped according to their general status of pubertal development (pre-early puberty: Tanner stageII). Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys, but not pre-early pubertal girls and boys. Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls. Changes in hypothalamic-pituitary-adrenal (HPA) axis function that occur during puberty may have implications for immediate and long-term adolescent health.

Altered salivary dehydroepiandrosterone levels in major depression in adults

BACKGROUND The authors sought to examine whether levels of dehydroepiandrosterone are abnormal in depression. METHODS Three groups of subjects aged 20-64 were studied: 44 major depressives, 35 subjects with partially or completely remitted depression, matched as far as possible for age and drug treatment, and 41 normal control subjects. Dehydroepiandrosterone and cortisol in saliva were determined from specimens taken at 8:00 AM and 8:00 PM on 4 days. RESULTS The mean age of the three groups did not differ. Dehydroepiandrosterone was lowered at 8:00 AM and 8:00 PM compared with control subjects. Values for the remitted group were intermediate. Dehydroepiandrosterone levels at 8:00 AM correlated negatively with severity of depression and were not related to drug treatment or smoking, but decreased with age (as expected). Cortisol was elevated in depression in the evening. The molar cortisol/dehydroepiandrosterone ratio also differentiated those with depression from the control group. CONCLUSIONS Lowered dehydroepiandrosterone levels are an additional state abnormality in adult depression. Adrenal steroid changes are thus not limited to cortisol. Because dehydroepiandrosterone may antagonize some effects of cortisol and may have mood improving properties, these findings may have significant implications for the pathophysiology of depression.