Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

BACKGROUND: Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state. METHODS: Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders. RESULTS: Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia. CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Hot and cold executive functions in youth with psychotic symptoms.

BACKGROUND: Psychotic symptoms are common in children and adolescents and may be early manifestations of liability to severe mental illness (SMI), including schizophrenia. SMI and psychotic symptoms are associated with impairment in executive functions. However, previous studies have not differentiated between 'cold' and 'hot' executive functions. We hypothesized that the propensity for psychotic symptoms is specifically associated with impairment in 'hot' executive functions, such as decision-making in the context of uncertain rewards and losses. METHODS: In a cohort of 156 youth (mean age 12.5, range 7-24 years) enriched for familial risk of SMI, we measured cold and hot executive functions with the spatial working memory (SWM) task (total errors) and the Cambridge Gambling Task (decision-making), respectively. We assessed psychotic symptoms using the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia interview, Structured Interview for Prodromal Syndromes, Funny Feelings, and Schizophrenia Proneness Instrument - Child and Youth version. RESULTS: In total 69 (44.23%) youth reported psychotic symptoms on one or more assessments. Cold executive functioning, indexed with SWM errors, was not significantly related to psychotic symptoms [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.85-2.17, p = 0.204). Poor hot executive functioning, indexed as decision-making score, was associated with psychotic symptoms after adjustment for age, sex and familial clustering (OR 2.37, 95% CI 1.25-4.50, p = 0.008). The association between worse hot executive functions and psychotic symptoms remained significant in sensitivity analyses controlling for general cognitive ability and cold executive functions. CONCLUSIONS: Impaired hot executive functions may be an indicator of risk and a target for pre-emptive early interventions in youth.

Like father like daughter: sex-specific parent-of-origin effects in the transmission of liability for psychotic symptoms to offspring.

Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8-24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43-4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61-2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.

The effects of lithium carbonate on healthy volunteers: mood stabilization?

A 2-month lithium-placebo double-blind cross-over study was carried out with 17 healthy volunteers. Their mood was self-rated: twice daily (AM, PM) with the Visual Analogue Mood Scale (VAMS); weekly with the analogue scales for subjective states and body symptoms; and three times (basal and at the end of each treatment period) with the Profile of Mood States (POMS). Memory and reaction time were also assessed, but did not show any change. The mean VAMS score decreased during lithium treatment, but the mean mood variability, a measure of the mean successive differences between consecutive mood ratings (delta squared), did not change significantly. There was a tendency toward decreased mood variability on lithium, both during the full 1-month treatment period and in the last week of treatment, when all volunteers had a lithium serum level ranging from 0.6 to 1.0 mEq/liter. The lower mean VAMS scores on lithium could be attributed to lithium-induced dysphoric mood as recorded on the analogue scales and POMS. However, very large inter- and intraindividual differences in response to lithium were observed. Actually, lithium even had an opposite effect on some volunteers' mood. The data and problems involved with assessment of mood and its changes are discussed.

Interaction of cannabidiol and alcohol in humans.

Six male and four female healthy volunteers were given oral placebo (glucose capsule and orange juice), cannabidiol (CBD 200 mg capsule and orange juice), alcohol (1 g/kg in orange juice and glucose capsule), and CBD (200 mg capsule) plus alcohol (1 g/kg in orange juice) in a double-blind, crossover, randomized design. Treatments were spaced one week apart. Parameters measured were a finger tap test (motor performance), cancellation and differential aptitude tests (psychomotor performance), a 1-min time production task, subjective effects (66 item adjective-pair semantic differential), and breathalyzer estimations of blood alcohol levels. Compared to placebo, alcohol and alcohol plus CBD, but not CBD alone, produced significant impairments of motor and psychomotor performances, overestimations of time production and subjective responses indicating an accurate self-perception of their intoxication and deficits. The combination of alcohol plus CBD resulted in significantly lower blood alcohol levels compared to alcohol given alone, however, there were few differences observed between the pharmacological effects of the two alcohol conditions. Thus, the inactivity of CBD, a major marijuana constituent, on motor and mental performance and effects also extends to its interaction with alcohol.

Effects of desipramine and total sleep deprivation on hormonal levels of healthy subjects.

Plasma prolactin (PRL) and growth hormone (GH) were serially measured over a 5-hour morning period in healthy subjects who twice received a single oral dose of 100 mg desipramine (DMI). The study was carried out both after a regular night of sleep and after 1 night of total sleep deprivation. Clinical studies have suggested that sleep deprivation could potentiate the therapeutic effects of antidepressants, and there were reports on DMI stimulation of GH. The basal PRL levels decreased after sleep deprivation, but subsequently increased after DMI, whereas the same dose of DMI did not affect PRL in the absence of after DMI, whereas the same dose of DMI did not affect PRL in the absence of sleep deprivation. The GH levels increased substantially (8- to 10-fold) after DMI in both experimental conditions. Sleep deprivation neither changed GH basal levels nor potentiated the DMI-induced GH increase.

The effects of REM sleep deprivation on striatal dopamine receptor sites.

3H-Spiroperidol binding to dopamine receptor sites of rat striatal tissue was studied following 24, 48, 72 and 96 hr of rapid eye movement sleep deprivation (REM dep.). The density of dopamine receptor binding sites (Bmax) was decreased after 48, 72, and 96 hr of REM dep. The apparent dissociation constant (KD) decreased after 96 hr, indicating an increase in apparent affinities. The control experimental animals also presented a time-dependent decrease of Bmax and KD as compared to unhandled controls. These results suggest that dopaminergic mechanisms may indeed be involved in the effects of REM sleep deprivation and/or stress.

The excitatory effect of ethanol: absence in rats, no tolerance and increased sensitivity in mice.

Three questions related to ethanol's stimulating effect (ESE) were studied. The first referred to the reported absence of tolerance to ESE in mice. It was determined whether tolerance would develop if the period of ethanol treatment were extended significantly beyond those normally found in the literature. No evidence of tolerance to ESE was found over a 5-month period of treatment. The second issue related to the possibility that mice not only do not develop tolerance but actually become more responsive to ESE after chronic exposure. A dose of ethanol that acutely did not produce a significant activating effect did induce a marked excitation after the animals were chronically treated with ethanol. Finally, the issue was addressed of whether the absence of ESE in some strains of rats could in part be due to a masking effect by the depressant component of this drug. To test this possibility rats were treated with ethanol for a 4-month period. Tolerance to the depressant effect was observed but no ESE was detected.

Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine.

REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre-1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg-1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.

Lack of agreement between the salivary flow and finger-sweat print methods for the determination of the anticholinergic effects of antidepressant drugs.

The purpose of the present study was to compare the extent of salivary flow and finger sweating after single acute oral doses of mianserin (30 mg), amitryptiline (75 mg), imipramine (75 mg) and maprotiline (75 mg) and placebo in healthy volunteers in a double-blind assay. Maprotiline and mianserin were less active in reducing salivary flow but were more active than amitryptiline and imipramine in reducing finger sweating. The lack of association between these methods for the measurement of the anticholinergic effect of antidepressant drugs is analyzed in terms of possible mechanisms for the control of palmar sweating.

Analysis of Impurity Content and Transport in Tokamak Plasmas Using Low-Resolution XUV Spectra.

Two experiments were performed to determine whether impurity content and transport information could be extracted from low-resolution XUV spectra recorded from a simple spectroscopic diagnostic that utilized a flat multilayer mirror as the dispersive element. The first experiment, at the DIII-D tokamak, compared MLM spectra to higher-resolution spectra and found that the low-resolution MLM spectra were sufficient to distinguish changes in impurity emission patterns. The results demonstrated the feasibility of building simple MLM-based diagnostics for impurity monitors in the harsh environment of future tokamaks. The second experiment, at the Texas Experimental tokamak, compared MLM spectra to those produced by an impurity transport code coupled to a collisional-radiative model. The comparison showed that it is possible to distinguish changes in impurity transport from low-resolution MLM spectra.

Near normal incidence spectroscopy of a Penning ionization discharge in the 110-180 A range with flat multilayer mirrors.

Al III to Al v spectra emitted from a Penning ionization discharge have been recorded in the 110-180 i range using two flat multilayer mirrors (Mo/Si and Mo/B(4)C) as dispersive elements in a near normal incidence configuration.

Lack of effect of intravenous hypertonic glucose on the intensity of alcohol intoxication induced experimentally and observed in patients of an emergency room.

In the present paper, two experiments are performed to test the efficacy of the intravenous administration of hypertonic glucose (25 or 50%) in alcoholic intoxication. In a first experiment, 10 healthy, nonstarved volunteers, received 15 min after the ingestion of 1.0 g/kg alcohol, 40 ml of 25% glucose i.v., the same volume of 0.9% NaCl or no injection. According to evaluations performed at several time intervals up to 2 h after alcohol ingestion, no difference among the 3 conditions was observed either in the intensity of alcohol intoxication or on blood alcohol levels. In a second experiment, blood glucose and alcohol levels were evaluated in 80 alcoholized patients in an emergency room. The mean glycemic value was 94 mg/100 ml. No difference was found by comparing this value with that presented by nonalcoholized patients. The 80 patients were distributed in two groups of 40 each: one of them was intravenously administered 40 ml of glucose 50% while the other was injected with saline. About 20-30 min later the patients of both groups were clinically evaluated by the physician on duty, being considered equally improved regardless of the injection. The self-evaluation by the patients provided similar results.

Peak reflectivity measurements of W/C, Mo/Si, and Mo/B(4)C multilayer mirrors in the 8-190-A range using both Kalpha line and synchrotron radiation.

Peak reflectivity measurements of W/C, Mo/Si, and Mo/B(4)C multilayer mirrors have been performed using line and synchrotron radiation in the 8-190 A wavelength range. Short wavelength measurements using a line source were corrected for nonmonochromatic and divergent incident radiation. Reflectivities of Mo/Si mirrors, measured with synchrotron radiation, ranged from 25 to 44% but decreased significantly around the Si absorption edge. Mo/B(4)C multilayer mirrors were measured that had peak reflectivities from 10 to 25% between 90 and 200 A and bandpasses as small as 3 A.

Salicilemia em voluntarios sadios apos a ingestao de aspirina sob a forma de comprimidos convencionais ou tamponados. / Salicylemia in healthy volunteers after ingestion of aspirin under the conventional or buffered tablets forms

Em esquema de duplo anonimato (doubleblind), 13 voluntarios sadios ingeriram 975mg de apirina, apresentada sob 3 tipos diferentes de comprimidos: aspirina sintetizada no Brasil por laboratorio nacional sem antiacidos(aspirina NQ-comprimidos A); aspirina NQ tamponada com glicinato de aluminio e carbonato de magnesio (comprimidos B); e aspirina comercial importada, sem antiacidos (comprimidos C). Dosagens plasmaticas mostraram que o nivel de salicilato ao fim de 2 horas era identico para os 3 tipos de comprimidos e que este nivel era atingido mais rapidamente com os comprimidos tamponados (B)