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Functional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS).We developed two algorithms to define dependency from items of UPDRS Part 2 and MDS-UPDRS Part 2 relating to basic ADLs (feeding, dressing, hygiene and walking, and getting out of a chair). We validated both algorithms using data from 1110 patients from six community-based PD incidence cohorts, testing concurrent validity, convergent validity, and predictive validity.Our optimal algorithm showed high specificity and moderate to high sensitivity versus SchwabEngland80% (specificity 95% [95% confidence interval (CI) 93-97] and sensitivity 65% [95% CI 55-73] at baseline; 88% [95% CI 85-91] and 85% [95% CI 79-97] respectively at five-years follow-up). Convergent validity was demonstrated by strong associations between dependency defined by the algorithm and cognition (MMSE), quality of life (PDQ39), and impairment (UPDRS part 3) (all p 0.001). Algorithm-defined dependency status also predicted mortality: HR for mortality in those dependent vs independent at baseline was 1.6 (95%CI 1.2-2.1) and in those dependent vs independent at five-years' follow-up was 2.2 (1.6-3.0).We have demonstrated the concurrent validity, convergent validity, and predictive validity of a UPDRS-/MDS-UPDRS-based algorithm to define functional dependency in PD. This can be used for studying dependency in any study where UPDRS or MDS-UPDRS part 2 data have been collected.

Aim and background Shift work, and especially night work, is associated with poor health. Nurses, work a variety of work schedules including night work. So far, few studies have specifically investigated sleep and health among intensive care nurses. Design and methods We investigated sleep, sleepiness, fatigue, subjective health complaints, anxiety and depression in 150 intensive care nurses (convenience sample representing a response rate of 56·2%). The nurses worked at two major University hospitals in Norway and answered a questionnaire survey. Results The intensive care nurses reported poorer sleep, more sleepiness, more fatigue, more anxiety and more depression compared to normative data. Poor sleep was reported by 70% and excessive sleepiness by 25% of the nurses; however, the design of the study did not allow us to determine the causes underlying these findings. Multiple linear regression analyses showed that age was positively associated with sleep problems, fatigue, subjective health complaints and anxiety and depression. In contrast, shift work experience was negatively associated with sleep problems, suggesting better coping with shift work over time. Conclusions Nurses working in intensive care units reported poorer sleep, more sleepiness, more fatigue, more anxiety and more depression compared to Norwegian norm groups. Age was positively related to these complaints, whereas shift work experience was negatively related to poor sleep. More studies are needed on strategies to improve sleep and health in nurses.

The objective was to compare the effects of two types of written material for insomnia in a randomized trial with follow-up after three months. Insomniacs were recruited through newspaper advertisements to a web-based survey with validated questionnaires about sleep, anxiety, depression, and use of sleep medications. A self-help book focusing on cognitive behavioral therapy for insomnia was compared to standard sleep hygiene advice; 77 and 78 participants were randomized to self-help book or sleep hygiene advice, respectively. The response rate was 81.9%. The self-help book gave significantly better scores on the sleep questionnaires compared to sleep hygiene advice. The proportion using sleep medications was reduced in the self-help book group, whereas it was increased in the sleep hygiene group. Compared to pre-treatment, the self-help book improved scores on the sleep (effect sizes 0.61-0.62) and depression (effect size 0.18) scales, whereas the sleep hygiene advice improved scores on some sleep scales (effect sizes 0.24-0.28), but worsened another (effect size -0.36). In addition, sleep hygiene advice increased the number of days per week where they took sleep medications (effect size -0.50). To conclude, in this randomized controlled trial, the self-help book improved sleep and reduced the proportion using sleep medications compared to sleep hygiene advice. The self-help book is an efficient low-threshold intervention, which is cheap and easily available for patients suffering from insomnia. Sleep hygiene advice also improved sleep at follow-up, but increased sleep medication use. Thus, caution is warranted when sleep hygiene advice are given as a single treatment.

We investigated the effects of the perfusion of gamma-aminobutyric acid(A) antagonist bicuculline in the dorsal raphe nucleus, on brain 5-hydroxytryptamine level and on sleep. Perfusion of 25 and 50 microM bicuculline into the dorsal raphe nucleus dose-dependently increased dorsal raphe nucleus 5-hydroxytryptamine level during sleep and wakefulness. Frontal cortex 5-hydroxytryptamine level was not affected by either 25 or 50 microM perfusion. 25 microM bicuculline produced only minimal effects on sleep. 50 microM decreased rapid eye movement sleep, slow wave sleep 1 and 2 and increased waking. Sleep changes leveled out towards the end of the bicuculline perfusion despite serotonin levels were still elevated. This suggests that an adaptation mechanism may take place in order to counteract the high serotonergic output, producing uncoupling between serotonin level and behavioural state. The results support the notion that gamma-aminobutyric acid is a strong modulator of dorsal raphe nucleus serotonergic neurons, and that this modulation is important in the regulation of slow wave sleep, rapid eye movement sleep and waking.

Many symptoms of human depressive disorders are also observed in animals after exposure to unpredictable stressors. The chronic mild stress (CMS) paradigm was developed in order to better model the human situation by using chronic mild stressors over a longer period. It is claimed that the model induces anhedonia in the animals, a core symptom of depression in humans. Despite the fact that the CMS model has a high degree of face validity, there are a number of laboratories in which the establishment of the model is less reliably observed. We have examined behavior (sexual activity and open field activity) together with hedonic measures (sucrose and saccharine intake) after exposure to CMS. CMS decreased male sexual activity (e.g. reduced capability to ejaculate) and increased activity in an open field test. The hedonic measures showed diverging results after CMS in our laboratory. Sucrose consumption was reduced, while saccharine consumption did not show a comparable change. It is concluded that CMS induces comparable alterations to some depression-like symptoms in humans. Saccharine consumption is not a reliable indicator of the hedonic responsiveness to CMS.

The objective was to compare the effects of two types of written material for insomnia in a randomized trial with follow-up after three months. Insomniacs were recruited through newspaper advertisements to a web-based survey with validated questionnaires about sleep, anxiety, depression, and use of sleep medications. A self-help book focusing on cognitive behavioral therapy for insomnia was compared to standard sleep hygiene advice; 77 and 78 participants were randomized to self-help book or sleep hygiene advice, respectively. The response rate was 81.9%. The self-help book gave significantly better scores on the sleep questionnaires compared to sleep hygiene advice. The proportion using sleep medications was reduced in the self-help book group, whereas it was increased in the sleep hygiene group. Compared to pre-treatment, the self-help book improved scores on the sleep (effect sizes 0.61-0.62) and depression (effect size 0.18) scales, whereas the sleep hygiene advice improved scores on some sleep scales (effect sizes 0.24-0.28), but worsened another (effect size -0.36). In addition, sleep hygiene advice increased the number of days per week where they took sleep medications (effect size -0.50). To conclude, in this randomized controlled trial, the self-help book improved sleep and reduced the proportion using sleep medications compared to sleep hygiene advice. The self-help book is an efficient low-threshold intervention, which is cheap and easily available for patients suffering from insomnia. Sleep hygiene advice also improved sleep at follow-up, but increased sleep medication use. Thus, caution is warranted when sleep hygiene advice are given as a single treatment.

Aim: The 5-HT1A receptor antagonist 4-Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (10 μm) was perfused into the dorsal raphe nucleus (DRN) to study simultaneously the effects of the drug on the DRN and frontal cortex extracellular serotonin (5-hydroxytryptamine, 5-HT) levels and concurring behavioural states. Methods: Waking, slow wave sleep and rapid eye movement sleep were determined by polygraphic recordings during microdialysis perfusion and extracellular sample collection. The samples were analysed by microbore high-performance liquid chromatography coupled with electrochemical detection for analysis of 5-HT. Results: p-MPPI perfusion into the DRN (n = 6) produced a sixfold 5-HT increase in the DRN during all behavioural states. The increased 5-HT level was most likely related to the blockage of 5-HT1A receptors in the DRN by p-MPPI. No significant effect was seen on sleep. Conclusion: Despite the dramatic increase in DRN extracellular 5-HT produced by p-MPPI, only a transient and nonsignificant effect on sleep was recorded. It is suggested that the usual coupling between 5-HT level and behavioural state may be lost when an excessive serotonergic output is pharmacologically achieved.

Chronic stress is linked to development of depression and may trigger neurobiological changes underlying the disease. Downregulation of the secretory peptide brain-derived neurotrophic factor (BDNF) and the transcriptional regulator calcium/cyclic-AMP responsive binding protein (CREB) have been implicated in stress and depression-related pathology in animal studies. When animals are exposed to the chronic mild stress (CMS) protocol, multiple depression-like symptoms are observed. Here we investigated the effect of CMS on BDNF protein expression and CREB activation in the dentate gyrus and hippocampus proper. Rats exposed for 5 weeks to repeated, unpredictable, mild stressors showed reduced BDNF expression and inhibited phosphorylation of CREB (Ser-133) in the dentate gyrus (-25.0%+/-3.5% and -29.7+/-7.3%, respectively), whereas no significant effects were observed in the hippocampus proper. CMS-treated rats consumed less sucrose compared to control rats, indicating a state of anhedonia. Moreover, phospho-CREB levels in the dentate gyrus were positively correlated with the animals' sucrose intake at the end of the CMS protocol. These results couple chronic mild stress to a downregulation of CREB activity and BDNF protein expression specifically within the dentate gyrus and support the possibility that the BDNF-CREB system plays an important role in the response to environmental challenges.

Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored by polygraphic recordings during the experiment. Sleep deprivation produced a gradual decline in extracellular serotonin levels, both in the hippocampus and in the frontal cortex. In order to investigate whether the reduction in serotonin was due to other factors than sleep deprivation, i.e. time of day effect, another experiment was performed. Here animals were allowed to sleep during most of the recording period. This experiment showed the expected changes in extracellular serotonin levels: consistently higher levels in the awake, non-sleep deprived animals compared to during sleep, but no time of day effect. The reduction in extracellular serotonin during sleep deprivation may suggest that serotonin does not play a major role in the mood-elevating effect of sleep deprivation. However, since 5-HT levels are strongly behavioral state dependent, by eliminating sleep, there may be a net increase in serotonergic neurotransmission during the sleep deprivation period. Copyright 2002 IBRO