Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform disorder. A regional cerebral blood flow study.

To measure prefrontal and subcortical activity during a cognitive task, we examined 19 newly diagnosed schizophrenics and patients with schizophreniform psychosis. Seven healthy volunteers served as controls. The patients were drug naive or had received neuroleptics for a few days only. Cerebral blood flow distribution was depicted by single photon emission computed tomography at rest and during activation with the Wisconsin Card Sorting Test. A significant relative activation deficit in the left inferior-prefrontal region was revealed during the Wisconsin Card Sorting Test in the patient group. Furthermore, the patients had impaired striatal suppression on the left side during the cognitive task. The test performance was significantly impaired in the patients. The inability to reduce striatal activity may be due to a lack of corticostriatal feedback during prefrontal activation.     

Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility.

The mutation fragilitas ossium (fro) was discovered in a random-bred stock of mice during an experiment aimed at detecting recessive lethal mutations after treatment of the postmeiotic germ cells of male mice with tris (1-aziridinyl)phosphine sulphide. The affected mice were moderately runted and had deformities in all four limbs. The radiological and histological findings indicate that the mutant is similar to human osteogenesis imperfecta. The ash content of long bones was lower in the mutant. A defect of type I collagen could not be detected. The electrophoretic patterns of alpha bands of type I and V collagen and CB derived peptides of type I collagen from bone and skin showed no abnormalities. The total collagen synthesis and secretion in cultures of dermal fibroblasts, as well as the gel electrophoresis of procollagen and collagen chains synthesized, and of their CB peptides, were the same as those found in the controls. The percentage of type I and type V collagen synthesized was similar; that of type III was lower in the mutants. Bone osteonectin was found to be decreased by 30% and bone sialoprotein by 5%. The mRNA level for osteonectin was decreased in the fibroblasts of the mutant by about 50%. Whether the defective expression of the osteonectin in fro/fro mice is due to a mutation in the gene itself or its regulatory site(s), or is secondary to other factors remains to be established. The fro/fro mouse may represent a model for some forms of human bone fragility without collagen abnormalities.     

Activation of glucocorticoid receptors and the effect of naloxone during hemorrhagic hypotension.

Evidence indicates that endogenous opioid peptides and glucocorticoids participate in the control of cardiovascular regulation during hemorrhagic shock. In the present study, we investigated a possible interaction between brain opioid peptides and adrenal corticosteroids regarding the control of arterial pressure during hemorrhage. The bleeding volumes required to lower arterial pressure to 80, 60 and 40 mmHg were studied in anesthetized sham-operated (SHAM) and adrenalectomized (ADX) rats. I.c.v. administration of 10 micrograms of naloxone resulted in a significant increase in the bleeding volume required to lower arterial pressure from 60 to 40 mmHg in SHAM animals, whereas no effect of naloxone was observed in ADX animals. Replacement therapy with a 100% corticosterone pellet (100 mg, s.c.), but not with a 12.5% corticosterone pellet (12.5 mg corticosterone and 87.5 mg cholesterol, s.c.), resulted in an effect of naloxone on the bleeding volume in ADX animals. The effect of replacement therapy could be inhibited by i.c.v. pretreatment with the synthetic glucocorticoid receptor antagonist, RU38486 (100 ng). These data suggest that (1) opioid mechanisms are involved in the regulation of blood pressure during hemorrhage, and (2) occupancy of glucocorticoid receptors is required for naloxone to exert its hemodynamic effect during hemorrhagic hypotension in ADX rats.     

Circulating immune complexes in pre-eclampsia.

Serum samples from 20 non-pregnant women, 30 women with normal pregnancy and 50 women with pregnancy associated with pre-eclampsia were tested for circulating immune complexes using the polyethyleneglycol precipitation method. A highly significant positive correlation was found between circulating immune complexes and severe pre-eclampsia (BP greater than 140/90 mm Hg, albuminuria greater than 0.25 g/l). In contrast to this the difference in immune complex levels between non-pregnant subject, normal pregnancy cases and patients with mild pre-eclampsia was not statistically significant. A significant positive correlation was found between the level of circulating immune complexes and the severity of albuminuria. These findings suggest that circulating immune complexes, though not seeming to play an aetiological role in pre-eclampsia may very well be involved in its pathogenesis.     

Criteria for the evaluation of the biochemical composition of bile]

The authors suggest additional criteria evidencing inflammations in the gallbladder and colloid stability of the bile: bile acid absorption and cholesterol sedimentation coefficients. Derivation of these coefficients is based on biochemical examination of the bile with measurements of bile acid, cholesterol, and bilirubin concentrations in both portions. The results of examinations of 99 subjects evidence the diagnostic value and specificity of the characteristics, and availability of this method for clinical practice.     

Inpatient treatment of children with multiple personality/dissociative disorders and their families

A number of children who are admitted for inpatient psychiatric treatment have experienced significant trauma and abuse. It is important to evaluate them for the presence of a DD. The variety, complexity, and subtlety of the symptomatic presentation of childhood MPD makes differential diagnosis difficult, and it is probable that many cases have been missed in the past. Detailed historical information and extensive behavioral observations in a variety of settings can assist in establishing the diagnosis and in delineating areas for therapeutic intervention. Hospitalization may be necessary to conduct an adequate evaluation, develop a therapeutic alliance, safely manage behaviors that are injurious to the child or others, and/or to diffuse potentially volatile family situations. All members of a multidisciplinary inpatient team play important roles in the achievement of successful therapeutic intervention with dissociating children and their families. Skilled family therapy is often an important adjunct to therapeutic interventions focused on the child, particularly when the parent also has MPD. Knowledge of the psychodynamic issues involved in dissociation can be used to develop behavioral interventions that are successful in decreasing the child's need to dissociate, improving his or her overall functioning, and help him or her gain mastery over problematic behaviors.     

Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia.

Extracellular 5-HT in the anterior hypothalamus/preoptic area (AH/POA) and caudate nucleus of the freely moving cat was measured using in vivo brain microdialysis. Administration of 8-OH-DPAT, a 5-HT1A receptor agonist that decreases 5-HT neuronal activity, decreased extracellular 5-HT in both brain areas. Extracellular 5-HT levels were also examined in relationship to the sleep-wake cycle, because previous data from our laboratory have indicated that behavioral state is the primary determinant of 5-HT neuronal discharge. As with 5-HT neuronal discharge, extracellular 5-HT was increased during active behavioral states and decreased during somnolent periods. These first two sets of findings confirm the ability of the microdialysis technique to measure physiological fluctuations in extracellular 5-HT levels and support the hypothesis that neuronal discharge is a major determinant of extracellular 5-HT levels. Levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) in the AH/POA were also responsive to changes in behavioral state and administration of 8-OH-DPAT, though fluctuations in extracellular 5-HIAA were less robust and temporally delayed. Finally, extracellular 5-HT and 5-HIAA were examined in the AH/POA during fever induced by systemic injection of the synthetic pyrogen muramyl dipeptide. Previous data from our laboratory have indicated that 5-HT neuronal activity is unaffected by this manipulation, though 5-HT has been implicated specifically in thermoregulation. Pyrogen-induced hypothermia produced no specific change in 5-HT efflux, because any changes noted could be accounted for by behavioral state changes. These data are consistent with the hypothesis that the brain serotonergic system is closely linked to the sleep-wake-arousal cycle. However, extracellular 5-HT may be involved in thermoregulatory processes as part of a global role in modulating neuronal activity in coordination with the behavioral state of the animal.     

Single-channel K+ currents recorded from the somatic and dendritic regions of cerebellar Purkinje neurons in culture

Voltage-sensitive K+ channels were studied in rat cerebellar Purkinje neurons in culture using the single-channel recording technique. Recordings in the cell-attached and outside-out configuration revealed multiple voltage-sensitive K+ channel types in patches from both the somatic and the dendritic regions. K+ channel types were present in all patches studied. The same channel types were observed in somatic and dendritic recordings. Channel types were identified by reversal potential, single-channel conductance, voltage sensitivity, and patterns of activity. In cell-attached patches recorded under physiological conditions, 3 channel types were identified. Mean single-channel conductances were 92, 57, and 12 pS. All 3 channel types were activated by membrane depolarization. Similar channel types were identified in inside-out and outside-out patches recorded under physiological conditions. Two additional channel types were identified in the outside-out patches, with mean single-channel conductances of 41 and 26 pS. In cell-attached recordings under symmetrical K+ conditions, 6 channel types were identified. Mean single-channel conductances were 222, 134, 39, 25, 14, and 15 pS. Channel types with mean conductances of 222, 134, and 39 pS required membrane depolarization for activation. A comparison of channel properties indicated that these channel types correlated with the 3 channel types observed in cell-attached patches under physiological conditions. The 3 smaller-conductance channel types (25, 14, and 15 pS) were active at potentials around rest or at hyperpolarized membrane potentials. Two K+ channel types (39 and 25 pS) were commonly associated with the late phase of extracellularly recorded spontaneous spike events, suggesting a functional role in the repolarizing phase of somatic and dendritic action potentials. These results demonstrate that voltage-sensitive K+ channels are a prominent component of both the somatic and the dendritic membrane of the cerebellar Purkinje neuron and support the view that multiple voltage-sensitive K+ channel types contribute to the membrane functions of both cellular regions in this CNS neuronal type.     

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.