Early visual information processing in schizophrenia compared to recurrent depression

Patients with schizophrenia have repeatedly shown deficits in early visual processing using backward masking (VBM) tasks. Whether this represents a specific dysfunction in schizophrenia is an unsolved question. Patients with recurrent unipolar depression represent an interesting comparison group to examine the question of specificity, but have never previously been assessed on VBM. In addition to comparing VBM performance in patients with schizophrenia and patients with depression, we wanted to examine the relations between VBM and clinical symptoms. Fifty-one patients with schizophrenia were compared to 49 patients with recurrent unipolar depression and 47 healthy controls. All subjects were administered a two-digit identification task in a no-masking and four masking conditions. Patients with schizophrenia performed significantly worse than normal controls on four of the five conditions. No significant difference was found between depression patients and normal controls. The effect of masking stimuli had no differential effects on the three groups. VBM correlated strongly with positive symptoms in the schizophrenia group.     

Funded research in psychosomatic medicine, medical psychology, and psychotherapy

This paper, summarizing the activities of the research task force of the German College of Psychosomatic Medicine (DKPM), reviews how research in psychosomatic medicine, medical psychology and psychotherapy has been funded by different institutions. The review reveals that psychosocial research has received considerable grants especially by the German Research Council and the Federal Ministry of Education and Research but also from other funding institutions. Besides an overview of potential sources for funding in the psychosocial disciplines, recommendations are formulated that might be helpful for raising research funds in the future.     

Tenascin-R as a repellent guidance molecule for newly growing and regenerating optic axons in adult zebrafish

In adult fish, in contrast to mammals, new optic axons are continuously added to the optic projection, and optic axons regrow after injury. Thus, pathfinding of optic axons during development, adult growth, and adult regeneration may rely on the same guidance cues. We have shown that tenascin-R, a component of the extracellular matrix, borders the optic pathway in developing zebrafish and acts as a repellent guidance molecule for optic axons. Here we analyze tenascin-R expression patterns along the unlesioned and lesioned optic pathway of adult zebrafish and test the influence of tenascin-R on growing optic axons of adult fish in vitro. Within intraretinal fascicles of optic axons and in the optic nerve, newly added optic axons grow in a tenascin-R immunonegative pathway, which is bordered by tenascin-R immunoreactivity. In the brain, tenascin-R expression domains in the ventral diencephalon, in non-retinorecipient pretectal nuclei and in some tectal layers closely border the optic pathway in unlesioned animals and during axon regrowth. We mimicked these boundary situations with a sharp substrate border of tenascin-R in vitro. Optic axons emanating from adult retinal explants were repelled by tenascin-R substrate borders. This is consistent with a function of tenascin-R as a repellent guidance molecule in boundaries for adult optic axons. Thus, tenascin-R may guide newly added and regenerating optic axons by a contact-repellent mechanism in the optic pathway of adult fish.     

Improvement in behavioral symptoms and advance of activity acrophase after short-term bright light treatment in severe dementia

Ten elderly subjects with severe dementia were given bright light (5000-8000 lux) for 45 min each morning for 4 weeks. Two rating scales of behavioral symptoms in dementia were used as outcome measures: Cohen-Mansfield Agitation Inventory (CMAI) and Behavior Pathology In Alzheimer's Disease Rating Scale (BEHAVE-AD), a scale for sleep-wake disturbances, and actigraphy to monitor activity rhythm. Behavioral symptoms improved with treatment. No changes in sleep-wake measures were found. There was an advance of the activity rhythm acrophase during treatment. These results suggest that short-time bright light improves behavioral symptoms and aspects of activity rhythm disturbances even in severely demented subjects.     

Reducing the duration of untreated first-episode psychosis: effects on clinical presentation

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.     

Localization of components of the renin-angiotensin system in the suprachiasmatic nucleus of normotensive Sprague-Dawley rats: part A. angiotensin I/II, a light and electron microscopic study

The central pacemaker of the mammalian circadian clock, identified in the suprachiasmatic nucleus (SCN), is of special interest for many chronomedical studies on neuropeptides. Based on its role in the modulation of blood pressure and vasopressin release, the distribution and function of the neuropeptide angiotensin II (ANG II) in the SCN became a target for several immunohistological studies. At the light microscopic level, the distribution of ANG II in the SCN is well known, but detailed information about the localization of ANG II in the SCN at the ultrastructural level is missing. To gain further insight in the functional aspects of ANG II in the SCN, we investigated on the subcellular localization of the neuropeptide ANG II and its precursor ANG I in the SCN. The current report presents a light and electron microscopic study on ANG I/II-immunoreactivity in the suprachiasmatic nucleus of normotensive Sprague-Dawley rats.     

Localization of components of the renin-angiotensin system in the suprachiasmatic nucleus of normotensive Sprague-Dawley rats: part B. angiotensin II (AT1)-receptors, a light and electron microscopic study

The dominant pacemaker of the mammalian circadian clock, located in the suprachiasmatic nucleus (SCN), is of special interest for many pharmacological, physiological and immunohistological studies on angiotensins and their receptors. Based on its role in the circadian modulation of blood pressure and vasopressin release, the distribution and function of the neuropeptide angiotensin II (ANG II) and its AT1-receptors (AT1) in the SCN became a target for several immunohistological studies. Though the distribution of ANG II and vasopressin in the SCN is well known at light microscopic level, detailed data concerning the AT1-receptor distribution in the SCN is missing. To confirm the mechanisms by which ANG II exerts its actions in the SCN, it is vital to understand how the brain renin-angiotensin system is organized at the cellular level, including the distribution of ANG II and the ANG II (AT1)-receptors as well as the protein-receptor complex. The current paper presents a light- and electron microscopic study on AT1-receptor-immunolabeling in the suprachiasmatic nucleus of normotensive Sprague-Dawley rats.     

Navigating toward fetal and maternal health: the challenge of treating epilepsy in pregnancy

A rational approach to the treatment of women of childbearing potential with epilepsy has been hampered by the lack of conclusive data on the comparative teratogenic potential of different antiepileptic drugs (AEDs). Although, several cohort studies on birth defects associated with AED use during pregnancy have been published, these have generally failed to demonstrate differences in malformation rates between AEDs, probably mainly due to insufficient power. In particular, pregnancies with new generation AEDs have been too few. In recent years, pregnancy registries have been introduced to overcome this problem--EURAP (an international collaboration), the North American, and the U.K. AED and pregnancy registries are observational studies that prospectively assess pregnancy outcome after AED exposure using slightly different methods. Each has enlisted 3-5,000 pregnancies in women with epilepsy, and the North American and the U.K. have released preliminary observations. Thus the U.K. registry reported a higher malformation rate with valproate, 5.9% (4.3-8.2%; 95% CI), than with carbamazepine, 2.3% (1.4-3.7%), and lamotrigine, 2.1% (1.0-4.0%). Most of the more recent cohort studies have also identified a nonsignificant trend toward a higher teratogenicity with valproate. These signals need to be interpreted with some caution since none of the studies to date have fully assessed the impact of possible confounders, such as type of epilepsy, family history of birth defects, etc. However, with increasing number of pregnancies it should be possible in the near future for the pregnancy registries to take such confounding factors into account and thus make more reliable assessments of the causal relationship between exposure to specific AEDs and teratogenic risks. While awaiting more conclusive results, it appears reasonable to be cautious in prescribing valproate to women considering to become pregnant if other suitable treatment alternatives, and with less teratogenic potential, are available. Any attempt to change treatment should, however, be accomplished well before conception. The importance of maintained seizure control must also be kept in mind, and the woman who needs valproate to control her seizures should not be discouraged from pregnancy, provided that counseling at the best of available knowledge is given.     

Effects of alkylphenols on redox status in first spawning Atlantic cod (Gadus morhua)

Offshore oil production releases large amounts of lipophilic compounds in produced water and into the ocean. The discharge of produced water from the Norwegian petroleum sector has increased from 26 million m3 in 1993 to 120 million m3 in 2001, and it continues to increase. Produced water contains significant amounts of alkylphenols, which have been reported to be estrogenic, causing endocrine disruption in fish. In year 2000, approximately 44 tons of alkylphenols were released on the Norwegian continental shelf in connection with discharge of produced water. Except from being estrogenic, relatively little is known about the effects of alkylphenols when released in the marine environment. Our objective was to study how alkylphenols affect the redox status in first spawning Atlantic cod (Gadus morhua) of both sexes. Model compounds tested included 4-tert-butylphenol (C4), 4-n-pentylphenol (C5), 4-n-hexylphenol (C6) and 4-n-heptylphenol (C7), all found in produced water. First spawning Atlantic cod were force-fed a mixture of these four alkylphenols, ranging between 0.02 and 80 ppm or 5 ppm 17beta-estradiol (E2), for 1 or 4 weeks. Increased hepatic total glutathione concentration in response to alkylphenol exposure was detected in female fish compared to control group after 1-week exposure, an effect not seen after 4 weeks. Furthermore, hepatic total glutathione concentration was sex dependent, where male fish sampled after 4 weeks had higher levels of glutathione than female fish. Increased glutathione reductase catalytic activities in both male and female fish were seen after exposure to 0.02 ppm alkylphenol mixture in 4 weeks. The glutathione S-transferase activity was only affected in male fish exposed to 0.02 ppm alkylphenols, and glucose-6-phosphate dehydrogenase activity increased in female fish exposed to 0.02 ppm alkylphenol mixture for 1 week. The increase of hepatic total glutathione content as well as the effects on glutathione reductase activities suggests that alkylphenol exposure affects the redox status in Atlantic cod.     

Plasma concentrations during naltrexone implant treatment of opiate-dependent patients

AIMS: To evaluate individual variations in plasma concentrations over time in patients with naltrexone implants. METHODS: Ten opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite beta-naltrexol. RESULTS: The median naltrexone C(max) was 12.3 (range 5.8-22.1) ng ml(-1), the median T(max) was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml(-1) was 55 (range 30-80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation. CONCLUSION: Marked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.