Cortisol production rate in posttraumatic stress disorder.

CONTEXT: Several authors have reported the unsuspected finding of low cortisol levels (urinary, salivary, and serum) in patients with posttraumatic stress disorder (PTSD). OBJECTIVE: Our objective was to assess concentrations of cortisol and its predominant metabolites, cortisol production rate (CPR), and glucocorticoid receptor (GR) binding characteristics in PTSD compared with normal subjects. DESIGN: Matched PTSD patients and control subjects had CPR determined by a stable isotope dilution technique after infusion of deuterated cortisol. Serum cortisol, urinary cortisol, and its metabolites were measured by gas chromatography/mass spectrometry. GR binding capacity (R(o)) and ligand binding affinity (K(d)) were measured in mononuclear leukocytes. SETTING: All subjects were tested during a 40-h admission in an inpatient clinical research center. PATIENTS AND PARTICIPANTS: Ten patients with PTSD were matched by age and gender with 10 controls. OUTCOME MEASURES: Statistical comparison was conducted for various measures of cortisol in PTSD patients and normal subjects. RESULTS: No statistical difference was found in mean level or circadian pattern of cortisol secretion using serum or salivary immunoassay detection methods. Although in the normal range, urinary cortisol by immunoassay showed statistically lower values over a 24-h period in PTSD patients compared with controls. This finding was not confirmed by gas chromatography/mass spectrometry determination of cortisol or its metabolites. CPR was not statistically different between these groups. GR also showed no alteration in R(o) or K(d) between the groups. CONCLUSION: The data indicate that PTSD in the chronic and unprovoked state is not characterized by an acute biological stress response.

Taurine release from the pineal-gland is stimulated via a beta-adrenergic mechanism.

Pineal glands were prelabeled in organ culture with [14C]taurine, and then treated with biogenic amines. The rate of release of [14C]taurine was rapidly elevated by low concentrations of norepinephrine, apparently acting through a beta-adrenergic mechanism. The release was probably not due to a nonspecific change in membrane permeability, as a comparable release was not seen with [14C]glycine and [14C]alpha-aminoisobutyric acid. These findings suggest that the release of taurine may be related to or a reflection of the early events in adrenergic activation of the pineal gland, such as hyperpolarization of pinealocytes. The released taurine might also have an extracellular role as it has been recently shown that extracellular taurine can interact with pineal beta-adrenergic receptors to stimulate melatonin production. Thus, the released taurine could possibly act as an extracellular feedback messenger.

Taurine: stimulation of pineal N-acetyltransferase activity and melatonin production via a beta-adrenergic mechanism.

Pineal glands convert [3H]tryptophan to [3H]N-acetylserotonin and [3H]melatonin in organ culture. Taurine treatment increases the rate of production of these compounds 40- and 25-fold respectively by stimulating the activity of N-acetyltransferase. This stimulation is blocked stereospecifically by L-propranolol, indicating that taurine is probably acting via beta-adrenergic receptors. Taurine is active in stimulating N-acetyltransferase activity in denervated glands, suggesting that it might interact directly with the beta-adrenergic receptor, and not by causing the release of norepinephrine from nerve terminals.

Uptake studies of taurine in vivo and its effects on the course of experimental focal epilepsy in rats.

The passage of orally administered taurine across the intestinal wall to the blood plasma and target sites of neuromuscular excitability has been studied. This has been correlated with the effect of repeated oral dosing on the manifestations of cobalt-induced epilepsy in the rat. The blood-brain barrier and the organ distribution of taurine uptake have important implications in testing its effect on hyperexcitability phenomena.

Neonatal encephalopathy: an indicator of early sexual maturation in girls.

Of 161 girls with neonatal encephalopathy who were prospectively assessed until 8 years of age, 7 (4.3%) demonstrated variable degrees of early sexual maturation. This finding was significantly greater than the accepted 0.6%, estimated for the general population. Four of the 7 girls with early sexual maturation had physical disabilities (i.e., 3 with cerebral palsy, 1 neurosensory deafness) which indicated that 10% of the 40 physically disabled girls had early sexual maturation. Three (2.5%) of 121 girls without physical disabilities matured early. Sexual maturation began 5 years or longer after the diagnosis of neonatal encephalopathy. An increased incidence of early sexual maturation in girls with neonatal encephalopathy indicates the importance of long-term follow-up of this population. This study provides an indication of a link between newborn illnesses causing neonatal encephalopathy and early sexual maturation in girls without progressive, structural, intracranial pathology and suggests further study of some girls previously diagnosed as having idiopathic precocious puberty.

A case of mistaken identity: a fourth ventricular tumor presenting as school phobia in a 12 year old boy.

A 12 year old boy was diagnosed as having overanxious disorder of childhood and school phobia. He was later found to be suffering from the effects of a cerebral tumor. Surgical removal of the tumor led to alleviation of the anxiety. The authors utilize this case to illustrate some aspects of differential diagnosis in child psychiatry. In particular, they point out the necessity of comprehensive physical examination in child psychiatry impatient units. The danger of attributing physical symptoms to functional illness purely in the absence of positive physical findings is noted. The importance of utilizing a biopsychosocial diagnostic model in child psychiatry is stressed.

Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates.

Corticotropin-releasing factor (CRF) is a neuropeptide involved in integrating the behavioral, autonomic, and hormonal responses to stress within the central nervous system. Patients suffering from depression have abnormal activity in stress responsive brain regions and elevated cerebrospinal fluid CRF. The DSM-IV criteria for major depressive disorder include behavioral changes such as depressed mood, anhedonia, and psychomotor agitation/retardation. We studied the effects of 434 microgram of CRF given intracerebroventricularly over 40 min in group and individually housed monkeys to examine the role of elevated levels of central CRF on behavior. CRF elicited a wide range of behaviors, which fell into three broad categories: anxiety-like, depressive-like, and externally oriented. Externally oriented behaviors decreased, and anxiety-like behaviors increased regardless of how the animals were housed. Interestingly, increased depressive-like behaviors were only observed when the animals were socially housed. In a separate experiment, we examined the effects of the same dose of CRF on the regional cerebral glucose metabolism of lightly anesthetized monkeys by using positron emission tomography and [(18)F]fluorodeoxyglucose. CRF infusion increased glucose metabolism in the pituitary/infundibulum, the amygdala, and hippocampus. These results indicate that increased central CRF tone affects primate behavior in a context-dependent manner, and that it activates limbic and stress-responsive regions. The fact that intracerebroventricular CRF increases depressive-like behavior in socially housed animals and increases activity in limbic brain regions may help explain the behavioral and metabolic alterations in humans with affective disorders, and this model could therefore have significant value in the development of novel antidepressant treatments.