Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's disease.

The aim of the present study was to identify the distribution of the second melatonin receptor (MT2) in the human hippocampus of elderly controls and Alzheimer's disease (AD) patients. This is the first report of immunohistochemical MT2 localization in the human hippocampus both in control and AD cases. The specificity of the MT2 antibody was ascertained by fluorescence microscopy using the anti-MT2 antibody in HEK 293 cells expressing recombinant MT2, in immunoblot experiments on membranes from MT2 expressing cells, and, finally, by immunoprecipitation experiments of the native MT2.

Auditory distraction in young and middle-aged adults: a behavioural and event-related potential study.

Cognitive tasks involving distraction are associated with an early age-related decline in performance. Involuntary shifts in attention to irrelevant stimulus features and subsequent reorientation were studied in young and middle-aged subjects focussing on behavioural and event-related potential (ERP) measures. Subjects were asked to discriminate between equiprobable short and long auditory stimuli.

High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light.

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.

The frontal predominance in human EEG delta activity after sleep loss decreases with age.

Sleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non-rapid eye movement sleep. We investigated age-related changes of the EEG response to sleep deprivation along the antero-posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions.

Orexins and their receptors in the human retina.

Objectives: Orexins A and B are neuropeptides involved in the regulation of feeding behavior, energy homeostasis and arousal. In the human retina, however, immunohistochemical localization of orexins and their receptors, OX-R1 and OX-R2, has not been ascertained.

Methods: We localized orexins A and B, OX-R1 and OX-R2 in the human retina using immunohistochemistry.

Waking up properly: is there a role of thermoregulation in sleep inertia?

We assume that alertness should be highest at the end of a sleep episode: it is not. There is always sleep inertia upon awakening, which can last minutes to hours, and whose underlying physiological mechanisms are largely unknown. Previously, we had found a functional relationship between the degree of distal vasodilatation (as measured by the distal-proximal skin temperature gradient (DPG) and sleepiness (as measured by subjective ratings), promoting rapid sleep onset.

Circadian modulation of sequence learning under high and low sleep pressure conditions.

Humans are able to learn complex sequences even without conscious awareness. We have studied the repercussions of circadian phase and sleep pressure on the ability to learn structured sequences using a serial reaction time task (SRT). Sixteen young healthy volunteers were studied in a 40-h "constant posture protocol" under high sleep pressure (i.

Serotonin transporter gene polymorphism and personality traits in primary alcohol dependence.

We tested the hypothesis of an association between the serotonin transporter (5-HTT) gene regulatory region polymorphism and the Temperament and Character Inventory (TCI) personality dimension of Harm Avoidance. For the study, 124 subjects seeking inpatient treatment for primary alcohol dependence were grouped by their 5-HTT genotype and assessed with the TCI. Genotypes differed statistically significantly in Harm Avoidance but not in any other personality trait.

Evening melatonin and bright light administration induce additive phase shifts in dim light melatonin onset.

In healthy young men, administration of a single light pulse (5000 lux for 3 hr) or a single melatonin pill (5 mg) at 20:40 hr under controlled constant routine conditions of <10 lux, yielded a phase delay and a phase advance, respectively, in the circadian marker of dim light melatonin onset 24 hr later. Phase shifts after combining the two interventions were additive. Melatonin suppression is not necessary for a phase shift by light, and melatonin is not a 'weak' Zeitgeber relative to bright light when ambient lighting is strictly controlled.

Circadian and wake-dependent modulation of fastest and slowest reaction times during the psychomotor vigilance task.

Performance on the psychomotor vigilance task (PVT) sensitively reflects a circadian modulation of neurobehavioral functions, as well as the effect of sleep pressure developing with duration of time awake, without being confounded by a learning curve. Sixteen healthy volunteers underwent two 40-h constant posture protocols in a balanced crossover design. During these protocols, either low sleep pressure conditions were attained by an alternating cycle of 150 min of wakefulness and 75 min of sleep (NAP) protocol, or high sleep pressure conditions were achieved by total sleep deprivation (SD) protocol.

Quality of life of living donors before and after living donor liver transplantation.

Living donor liver transplantation (LDLT) is becoming an established method for treatment of terminal liver disease in adults. After resection of the right hepatic lobe, postoperative complications can arise in healthy donors, and even individual cases of death have been recorded. There remains, however, little research on the psychosocial aspects in living donors before and after LDLT.

Human sleep spindle characteristics after sleep deprivation.

Objective: Sleep spindles (12-15 Hz oscillations) are one of the hallmarks of the electroencephalogram (EEG) during human non-rapid eye movement (non-REM) sleep. The effect of a 40 h sleep deprivation (SD) on spindle characteristics along the antero-posterior axis was investigated.

Methods: EEGs during non-REM sleep in healthy young volunteers were analyzed with a new method for instantaneous spectral analysis, based on the fast time frequency transform (FTFT), which yields high-resolution spindle parameters in the combined time and frequency domain.

Chronobiology and mood disorders.

The clinical observations of diurnal variation of mood and early morning awakening in depression have been incorporated into established diagnostic systems, as has the seasonal modifier defining winter depression (seasonal affective disorder, SAD). Many circadian rhythms measured in depressive patients are abnormal: earlier in timing, diminished in amplitude, or of greater variability. Whether these disturbances are of etiological significance for the role of circadian rhythms in mood disorders, or a consequence of altered behavior can only be dissected out with stringent protocols (eg, constant routine or forced desynchrony).

Minimally invasive technique based on ultraslow ultrafiltration to collect and store time profiles of analytes.

A device is described to collect and store continuously time profiles of analytes over periods of 24 h suitable to sample freely moving individuals (humans and animals). The device consists of a hollow fiber ultrafiltration probe, a long capillary and a nonmechanical unit (a disposable medical syringe) driven by vacuum to withdraw fluid. The principle is that at low rates (< or = 100 nL/min), sample fluid is collected through the ultrafiltration probe into the capillary.

Safety of injectable opioid maintenance treatment for heroin dependence.

Background: There is a growing debate about injectable opioid treatment programs in many Western countries. This is the first placebo-controlled study of the safety of injectable opioids in a controlled treatment setting.

Methods: Twenty-five opioid-dependent patients on intravenous (IV) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo.

Seasonality in affective disorders in Switzerland.

Objective: To estimate the prevalence of seasonal affective disorder (SAD) and its subsyndromal form (S-SAD) in Switzerland (47 degrees N).

Method: A representative sample from all three language areas of Switzerland (n = 980) were given a structured telephone interview using the extended Seasonal Pattern Assessment Questionnaire (SPAQ+). A smaller, but also representative sample in the city of Basel filled in the SPAQ+ form as well as undergoing a structured diagnostic interview.

Regional differences in the circadian modulation of human sleep spindle characteristics.

Electroencephalographic oscillations in the sleep spindle frequency range (11-16 Hz) are a key element of human nonrapid eye movement sleep. In the present study, sleep spindle characteristics along the anterior-posterior axis were analysed during and outside the circadian phase of melatonin secretion. Sleep electroencephalograms were recorded during naps distributed over the entire circadian cycle and analysed with two different methodological approaches, the classical fast Fourier transform in the frequency-domain and a new method for instantaneous spectral analysis, the fast time frequency transform that yields high-resolution parameters in the combined time-frequency-domain.

Leptin levels of alcohol abstainers and detoxification patients are not different.

Aims: Leptin is a cytokine-type peptide hormone, recently implicated as a putative state marker of alcohol use and in craving. Our goal was to evaluate the potential of leptin as a state and trait marker and to rule out the role of current alcohol intoxication on leptin levels.

Methods: Eighteen alcohol withdrawal patients (16 males, 2 females) whose blood contained 202 mg/dl (median) of ethanol at hospitalization, who had a median age of 43.

Successful therapy of tardive dyskinesia in a 71-year-old woman with a combination of tetrabenazine, olanzapine and tiapride.

There is no generally accepted treatment for tardive dyskinesia following intake of neuroleptics. Many compounds with effects on serotonine, GABA, cholinergic or dopamine receptors have been clinically useful. We report on a 71-year-old female patient suffering from orofacial tardive dyskinesia after treatment with haloperidol, which did not respond to monotherapy with antidyskinetic drugs.

Role of melatonin in the regulation of human circadian rhythms and sleep.

The circadian rhythm of pineal melatonin is the best marker of internal time under low ambient light levels. The endogenous melatonin rhythm exhibits a close association with the endogenous circadian component of the sleep propensity rhythm. This has led to the idea that melatonin is an internal sleep "facilitator" in humans, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms.

Eugen Bleuler and forensic psychiatry.

The list of Eugen Bleuler's writings shows that he grappled with forensic issues quite early, even before he became a full professor in 1898. Bleuler regularly prepared forensic criminal expert's reports himself until emeritus status was conferred on him in 1927. Analysis of his writings indicates that his position remained explicitly deterministic.

Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.

We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle.

Homeostatic control of slow-wave and spindle frequency activity during human sleep: effect of differential sleep pressure and brain topography.

The impact of a 40 h sleep deprivation versus a 40 h multiple nap paradigm on topographic and temporal aspects of electroencephalographic (EEG) activity during the subsequent recovery sleep was investigated in 10 young volunteers in a controlled 'constant posture' protocol. The accumulation of sleep pressure with extended wakefulness could be significantly attenuated by intermittent naps. The differential sleep pressure conditions induced frequency- and topographic-specific changes in the EEG slow wave range (0.

Alteration of internal circadian phase relationships after morning versus evening carbohydrate-rich meals in humans.

The effects of a single morning and evening carbohydrate-rich meal for 3 consecutive days on circadian phase of core body temperature (CBT), heart rate, and salivary melatonin rhythms were compared under controlled constant routine conditions. In 10 healthy young men entrained to a natural light-dark cycle with regular sleep timing, CBT and heart rate were significantly elevated for approximately 8 h after the last evening carbohydrate-rich meal (EM), and nocturnal melatonin secretion (as measured by salivary melatonin and urinary 6-sulphatoxymelatonin levels) was reduced, compared to the morning carbohydrate-rich meal (MM) condition. Thus, circadian phase could not be measured until the following day due to this acute masking effect.