Cortisol concentrations and the social significance of rank instability among wild baboons

Previous work has shown that dominant primates in stable social hierarchies in a number of species often have low basal cortisol concentrations, relative to subordinate individuals. In contrast, this trait appears to be lost during periods of social instability, probably reflecting the psychological stressfulness of the instability. The present study examined whether basal cortisol concentrations were elevated not only when the overall hierarchy was unstable, but also were elevated in individuals which, within a stable hierarchy, were nevertheless in the process of their own rank shifting. Study subjects were a population of male olive baboons living freely in a national reserve in East Africa, which could be anesthetized under conditions allowing for determination of basal cortisol concentrations. The instability of a particular rank was quantified by determining the percentage of dominance interactions that represented a reversal of the already established direction of dominance.

Highly unstable relationships with the rest of the males in the hierarchy did not predict elevated basal cortisol concentrations in an individual. Instead, it was the stability of interactions with males close in rank (within three steps in the hierarchy of the individual) which predicted cortisol concentrations: the greater the percentage of interactions that were reversals with the three nearest lower-ranking males, the higher the basal cortisol concentrations in an individual. In general, high rates of such reversal interactions indicated that the male was being challenged for his more dominant position.

In contrast, basal cortisol concentrations were not related to the extent of instability in a male's interactions with the three nearest higher-ranking males; high rates of such interactions indicated that the male instead was challenging those ahead of him in the hierarchy. Thus, the present data show that rank instability is not always an addrenocortical stimulant; it depends on whether the instability implies that the male is rising or declining in the hierarchy.     

Hypercortisolism among socially subordinate wild baboons originates at the CNS level

Recent studies suggest that the hypercortisolism and dexamathasone resistance of depression arise, at least in part, at the level of the brain, ie, cortisol-releasing factor (CRF) and/or other corticotropin-secretagogues are hypersecreted. This article suggests a similar cause of the hypercortisolism of social subordinance. Two troops of wild olive baboons, living freely in the Serengeti Ecosystem of East Africa, have been under long-term study. Consistently, in stable dominance hierachies, subordinate males are hypercortisolemic relative to dominant animals. Furthermore, hypercortisolemic males are dexamethasone resistant. There are no rank-related difference in cortisol clearance or adrenal sensitivity to corticotropin, suggesting a pituitary and/or neural locus of the hypercortisolism. Subordinate males were shown to secrete less corticotropin in response to a CRF-challenge than did dominant males. Following the logic used in similar studies with depressives, if subordinate males were hypercortisolemic despite decreased pituitary sensitivity to CRF, then this implies that the hyperactivity of the adrenocortical axis is driven at the level of the brain. Furthermore, subordinate males were hyporesponsive to CRF after administration of metyrapone, which blocks cortisol secretion and disinhibits the pituitary from feedback inhibition. Thus, the pituitary appears to have lost sensitivity to CRF itself in these low-ranking males. These observations are interpreted in light of behavioral data suggesting that these subordinate males are under sustained social stress.     

Depressive symptoms associated with dexamethasone resistance

Using split sample discriminant function analysis on a series of 63 consecutive depressed outpatients, the authors identified several items on the Hamilton Depression Rating Scale that were associated with dexamethasone resistance (late and middle insomnia, retardation, somatic and psychic anxiety, and obsessive-compulsive symptoms), and several items that were associated with dexamethasone suppression (genital symptoms, somatic-general symptoms, hypochondriasis, early insomnia, and depersonalization). The accuracy of the classification function was 100% for the index split sample, 84% for the overall sample, and 72% for the other split sample. The implications of these findings are discussed.     

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.     

Prevalence of white matter hyperintensities increases with age

White matter hyperintensities(WMHs) that arise with age and/or atherosclerosis constitute a heterogeneous disorder in the white matter of the brain. However, the relationship between age-related risk factors and the prevalence of WMHs is still obscure. More clinical data is needed to confirm the relationship between age and the prevalence of WMHs. We collected 836 patients, who were treated in the Renmin Hospital, Hubei University of Medicine, China from January 2015 to February 2016, for a case-controlled retrospective analysis. According to T2-weighted magnetic resonance imaging results, all patients were divided into a WMHs group(n = 333) and a non-WMHs group(n = 503). The WMHs group contained 159 males and 174 females. The prevalence of WMHs increased with age and was associated with age-related risk factors, such as cardiovascular diseases, smoking, drinking, diabetes, hypertension and history of cerebral infarction. There was no significant difference in sex, education level, hyperlipidemia and hyperhomocysteinemia among the different age ranges. These findings confirm that age is an independent risk factor for the prevalence and severity of WMHs. The age-related risk factors enhance the occurrence of WMHs.     

EEG coherence obtained from an auditory oddball task increases with age.

Changes in coherence with aging during cognitive tasks have, until now, not been investigated. However, several fMRI and positron emission tomography studies of cognitive tasks have found increased bilateral activity in elderly subjects. Changes in coherence with aging during a cognitive task were investigated to see if EEG coherence was present in older adults. An auditory oddball task, which is a widely used test for cognitive function, was used. Eleven young adults (27.8 +/- 4.8 years, six females) and 10 older adults (61.3 +/- 4.6 years, six females) were studied, and both interhemispheric and long- and short-range intrahemispheric coherence were considered. Higher interhemispheric coherence was found in the older subjects in the delta band. Short intrahemispheric coherence was also increased in the theta, delta, and alpha bands. Higher coherence, although not significantly different, was also found for all other coherence types and bands, except for long intrahemispheric coherence in the low gamma band. The results presented here provide the first evidence that aging is associated with increased EEG coherence during a relatively easy cognitive task.     

Susceptibility to pilocarpine-induced seizures in rats increases with age

Systemic administration of high doses of the cholinergic agonist pilocarpine induces motor limbic seizures in rats. Susceptibility to the convulsant effects of pilocarpine increases during adult life: the threshold dose for generalized seizures is essentially constant from age 30 to 70 days, but decreases thereafter, particularly beyond age 100 days. The increase in seizure susceptibility continues up to at least age 200 days, (the oldest age studied).     

Incidence of cancer among persons with schizophrenia and their relatives

BACKGROUND: It has repeatedly been reported that the risk for cancer in patients with schizophrenia is different from that of the general population, specifically a lower risk for lung cancer despite increased smoking. Confirmation of these associations could lead to hypotheses on shared risk or protective factors, either genetic or environmental. METHODS: From Finland's National Hospital Discharge and Disability Pension registers, Helsinki, we identified a cohort of 26 996 individuals born between 1940 and 1969 and treated for schizophrenia between 1969 and 1991. They were followed up for cancer from 1971 to 1996 by record linkage with the Finnish Cancer Registry, yielding 446 653 person-years at risk, and standardized incidence ratios (SIRs) were calculated. Likewise, 39 131 parents and 52 976 siblings of the patients with schizophrenia were followed up to explore familial genetic hypotheses on deviations in cancer risk. RESULTS: In patients with schizophrenia, an increased overall cancer risk was found (724 cases observed vs 619 expected; SIR, 1.17; 95% confidence interval [CI], 1.09-1.25). Half of the excess cases were attributable to lung cancer (SIR, 2.17; 95% CI, 1.78-2.60), and the strongest relative increase in risk was in pharyngeal cancer (SIR, 2.60; 95% CI, 1.25-4.77). Cancer incidence in siblings (SIR, 0.89; 95% CI, 0.83-0.94) and parents (SIR, 0.91; 95% CI, 0.89-0.93) was consistently lower than that in the general population. CONCLUSION: Although specific lifestyle factors, particularly tobacco smoking and alcohol consumption, probably account for the increased cancer risk in patients with schizophrenia, the decreased risk in relatives would be compatible with a postulated genetic risk factor for schizophrenia offering selective advantage to unaffected relatives.     

Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone

Approximately 50% of depressed patients are resistant to the cortisol-suppressing effect of dexamethasone. To determine if glucocorticoid resistance could be a more generalized phenomenon in depressed patients, mitogen stimulation tests were performed on lymphocytes from 12 depressed patients and 12 control subjects before and after dexamethasone administration. Suppression of serum cortisol following administration of 1 mg of dexamethasone in four depressed patients and 11 control subjects was associated with a decreased lymphoproliferative response, but no such change occurred in the eight depressed patients and the single control subject who did not suppress cortisol. The dexamethasone-induced changes in the mitogen responses were positively correlated with the highest postdexamethasone serum cortisol values.     

Influence of age on the cortisol response to dexamethasone

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.     

Normal and injury-induced sympathetic innervation of rat dorsal root ganglia increases with age

In rats, partial injury to a peripheral nerve often leads to sympathetically maintained pain (SMP). In humans, this condition is especially apparent in the elderly. Nerve injury also causes perivascular sympathetic axons to sprout into the dorsal root ganglion (DRG), forming a possible anatomical substrate for SMP. Here, we describe the effects of chronic sciatic nerve constriction injury (CCI) in young (3 months) and old (16 months) rats on neuropathic pain behavior and on sympathetic sprouting in DRG. Behavioral tests assessed changes in thermal allodynia and hyperalgesia and in mechanical allodynia. We found that 1) sympathetic innervation of the DRG increased naturally with age, forming pericellular baskets mainly around large DRG neurons, and that sympathetic fibers were often associated with myelinated sensory axons; 2) sympathetic fiber density following CCI was also greater in old than in young rats; and 3) in old rats, thermal allodynia was less pronounced than in young rats, whereas thermal hyperalgesia and mechanical allodynia were more pronounced. These results highlight the possibility that sympathetic sprouting in the DRG is responsible for the sympathetic generation or maintenance of pain, especially in the elderly. J. Comp. Neurol. 394:38–47, 1998. © 1998 Wiley-Liss, Inc.     

Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures

Purpose: Several studies have indicated that psychogenic nonepileptic seizures (PNES) are associated with psychological trauma, but only a few studies have examined the associations with neurobiologic stress systems, such as the hypothalamus–pituitary–adrenal (HPA) axis and its end‐product cortisol. We tested several relevant HPA‐axis functions in patients with PNES and related them to trauma history. Methods: Cortisol awakening curve, basal diurnal cortisol, and negative cortisol feedback (using a 1 mg dexamethasone suppression test) were examined in 18 patients with PNES and 19 matched healthy controls (HCs) using saliva cortisol sampling on two consecutive days at 19 time points. Concomitant sympathetic nervous system (SNS) activity was assessed by analyzing saliva α‐amylase (sAA). Results: Patients with PNES showed significantly increased basal diurnal cortisol levels compared to HCs. This effect was driven mainly by patients reporting sexual trauma who showed a trend toward higher cortisol levels as compared to patients without a sexual trauma report. Importantly, the increased basal diurnal cortisol levels in patients were not explained by depression, medication, or smoking, or by current seizures or group differences in SNS activity. Discussion: This is the first study showing that basal hypercortisolism in patients with PNES is independent of the acute occurrence of seizures. In addition, basal hypercortisolism was more pronounced in traumatized patients with PNES as compared to nontraumatized patients with PNES. These findings suggest that HPA‐axis activity provides a significant neurobiologic marker for PNES.