Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.     

Measurement of maximum variability within event related potentials in schizophrenia.

One limitation of averaging individual late component event related potential (ERP) responses is that a single average ERP cannot reflect the variability of responses from epoch to epoch. In this article, we describe a method to quantify this variability and determine if any part of the overall ERP reflects a maximum variance through the use of response variance curves. We then apply this method to one disorder, schizophrenia, in which variability of information processing is hypothesized to underlie aspects of the symptomatology. Response variance curves in a group of unmedicated schizophrenic patients reveal systematic differences, maximal between 190 and 250 ms, compared with those in a group of medicated schizophrenic patients and normal control subjects.     

Longterm neurological complications of chronic, habitual cocaine abuse.

We review and expand the results of several previously published studies on computed tomographic and electroencephalographic correlates of chronic, habitual cocaine abuse in order to present a complete spectrum of the longterm neurological complications of cocaine abuse. We argue that prolonged and frequent cocaine abuse leads to biochemical and vascular cerebral insults that eventually may cause functional and structural abnormalities affecting predominantly the fronto-temporal areas.     

Chiari II malformation: MR imaging evaluation

The purpose of this study was to explore the value of high-detail MR imaging in the diagnosis of the Chiari II malformation. Twenty-four patients with known Chiari II malformation as diagnosed by CT scanning were evaluated with cranial MR scans. Two patients also had spine scans. The sagittal-plane images were the most informative, and abnormalities of the telencephalon, diencephalon, mesencephalon, rhomboencephalon, upper spinal cord, and mesencephalon were shown extremely well. We found MR to be an easy and accurate method for demonstrating the abnormalities of the Chiari II malformation, and it is our procedure of choice.     

Altered turnover and synthesis rates of lung surfactant following thoracic irradiation

Between 2-6 weeks after thoracic irradiation with 10 Gy X rays, when levels of surfactant in the alveoli show the greatest increase, there is a reduction in the rate of radioactivity loss from 3H-choline labeled disaturated phosphatidylcholine from the lung. This indicates a reduced turnover of surfactant. Discrepancies between the halving times for specific activity and for total radioactivity of the disaturated phospholipids suggest that at between 2 and 3 weeks post-irradiation, removal and degradation of surfactant almost ceases, but that synthesis continues normally. However, by 3 weeks post-irradiation, choline-3H incorporation into disaturated phosphatidylcholine suggests that surfactant synthesis is increased about two-fold. The reduced number of macrophages recovered from alveolar lavage between about 2 and 6 weeks post-irradiation may indicate a reason for the lengthened turnover times of surfactant over this period. Nevertheless the stimulated surfactant production that takes place from about 3 weeks onward suggests an additional active response to radiation or to radiation damage by the type II pneumonocytes. These studies confirm that the maximum levels of alveolar surfactant seen at 3 weeks post-irradiation result from a different lung response than that responsible for the increase in surfactant, which occurs within hours of irradiation.     

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.     

Nonreceptor binding of human chorionic gonadotropin (hCG): detection of hCG or a related molecule bound to endometrial tissue during pregnancy using labeled monoclonal antibodies that bind to exposed epitopes on the hormone

When hCG adsorbs to surfaces, including membranes from tissues that lack specific hCG receptors, it adsorbs with a particular orientation. Some sites on the alpha- and beta-subunits project away from the surface and can be detected with radiolabeled monoclonal antibodies. Other epitopes, which are located on a region on the hormone that presumably contacts the surface, lose their ability to bind antibody. Using antibodies specific for epitopes on hCG which remain exposed and can be detected when the hormone is adsorbed to rat brain homogenates, we found hCG or closely related substances bound to progestational decidual tissues. Immunologically reactive material adsorbed to the decidual tissue increased and decreased in parallel with the serum levels of hCG throughout pregnancy. Binding of labeled monoclonal antibody to substances similar or identical to hCG in other tissues, including placenta and fetal lung, but not red cells, also was identified. Unlike material adsorbed to decidual tissues, receptor-bound hCG was not recognized by any of our alpha-subunit-specific antibodies. This finding suggests either that the adsorbed hormone has a different orientation than receptor-bound hormone or that the adsorbed hormone has dissociated into subunits. These studies represent the first detection of nonreceptor binding of hCG or related molecules to tissues lacking receptors or presumed not to synthesize the hormone. The role of nonreceptor-bound hCG, if any, is unknown. Other than its effects on stimulation of luteal steroidogenesis during early pregnancy, the role of hCG during most of pregnancy has not been determined. Conceivably, the nonreceptor binding we identified is related to a role for hCG in pregnancy that is not associated with an action on the ovarian LH receptor.     

Importance of spinal noradrenergic pathways in cardiovascular reflexes and central actions of clonidine and alpha-methyldopa in the rabbit

We have examined in conscious rabbits the chronic effects of 6-hydroxydopamine (6-OHDA)-induced local lesions of the spinal noradrenaline (NA) pathways on (i) resting mean arterial pressure (MAP) and heart rate (HR), (ii) the nasopharyngeal pressor response, (iii) the sympathetic component of the baroreceptor-heart rate reflex (iv) the acute responses to intracisternal (i.c.) clonidine and alpha-methyldopa (alpha-MD), and (v) the acute NA release response produced by i.e. 6-OHDA. One month after injection of 6-OHDA (40 nmol in 4 microliters) into the first cervical spinal cord segment (C1), the NA content was reduced to 29% in C2, 45% in T4 and 61% in L3 with little non-specific damage. Basal MAP was 14% higher (P less than 0.05) than in sham-operated rabbits suggesting increased vasoconstrictor tone. Basal cardiac sympathetic tone was enhanced, but a corresponding increase in cardiac vagal tone resulted in little net effect on resting HR in the spinal NA-depleted group. Spinal NA lesions attenuated the nasopharyngeal pressor reflex by 27% in baroreceptor-intact rabbits and by 38% in sino-aortically denervated (SAD) animals. The lesion did not affect HR range, gain and BP50 of the sympathetic baroreflex. In SAD rabbits, the acute MAP responses to i.c. 6-OHDA (early hypotension, late hypertension) were not affected by spinal NA depletion, but the early fall in HR (cardiac sympathetic inhibition) was abolished. The hypotension produced by i.c. clonidine or alpha-MD was not affected by the lesion, probably because many of the NA terminals in the lower thoracic and upper lumbar cord were still intact. Our results suggest that intraspinal NA fibers have a tonic inhibitory action on spinal preganglionic vasoconstrictor and cardiac motoneurons. The spinal NA neurons affecting vasomotor tone (but not cardiac sympathetic tone) are in turn inhibited by higher vasomotor centers receiving projections from the arterial and trigeminal afferents and thereby participate in vasoconstrictor reflexes.