- Email: [email protected]
Animal models of circadian disorders and their treatment with chronobiotics
5-18 Circadian Rhythms in Neuropsychiatry and SleepDisorders
34 ical and psychological bases for these disturbances. We will distinguish between the most common presentations in the nursing home and in ambulatory settings and focus on the challenges that these disturbances present to the caregivers. Treatments for these conditions are varied and include environmental alternation, behavioral modification, re-direction and other pychotherapeutic techniques, background music, and bright lights. Further, we will describe the traditional and more recent pharmacotherapeutic interventions as well as the current and recent research that is being conducted in this area.
M. Van Der Linden. Abstract not available at time of publication.
Circadian Rhythms in Neuropsychiatry and Sleep Disorders
I8-18-1 I The Roleof the Suprachiasmatic Nuclei (SCN) as a Biological Clock: Effects of Melatoninergic Substances
F.w. Turek, O. Van Reeth. Centre for Circadian Biology & Medicine, Northwestern University Evanston, Illinois, USA It has clearly been established that the hypothalamic SCN contain an endogenous circadian pacemaker(s) that regulates most, if not all, 24-hr rhythms in mammals. One of the rhythms regulated by the SCN is the production and release of the hormone, melatonin, from the pineal gland: a rhythm in which melatonin levels are normally high during the night and low during the day. While the presence of the pineal gland is not necessary for the expression of other circadian rhythms, there is now substantial evidence from studies on rodents that treatment with melatonin, or melatonin agonists, can influence behavioural and metabolic rhythms under both free-running and entrained conditions. The recent finding that the SCN contains a high concentration of specific melatonin receptors, coupled with the observation that the direct application of melatonin-related compounds to the SCN in vitro can alter the rate of firing of SCN neurons, has led to the hypothesis that at least some of the effects of melatonin on circadian rhythmicity may be due to its feedback on the very clock regulating the rhythm of melatonin. Taken together with data on humans indicating that melatonin andJor melatoninergic substances, can modify the sleep-wake cycle as well as other circadian rhythms, the studies in rodents have led to a surge in interest in the possible use of melatonin-related drugs for the treatment of circadian rhythm abnormalities. Of particular interest is the possible use of such drugs in the elderly who show a pronounced reduced amplitude in the rhythm of melatonin in association with fragmented sleep-wake cycles, and disturbed circadian rhythmicity.
I8-18-21
18-18-31 Sleep and Mood Disorders: Relationship to Circadian Rhythms T.A. Wehr, E. Leibenluft, P.1. Schwartz, E.H. Turner, N.E. Rosenthal. NIMH, Besthesda, Maryland, USA
18-17-61
Is-181
examine these disorders and to investigate pharmacological treatments, a number of animal models have been developed using both nocturnal and diurnal rodents. These models will be described and the effects of both melatonin and S20098 reported. Other situations in which sleep patterns are disrupted such as in the elderly and during drug withdrawal will also be discussed.
Animal Models of Circadian Disorders andTheir Treatment with Chronobiotics
J.R. Redman. Department of Psychology, Monash University, Clayton, Australia Circadian disorders are characterised by abnormal timing of behaviours and physiological processes such as sleep and wakefulness, body temperature or plasma hormone levels. The DSM-IV now lists three types of sleep-wake schedule disorders in which there is a mismatch between the normal sleep-wake schedule and the person's environment. These are Advanced or Delayed type, Disorganised type, and Frequently Changing type. It has recently been reported that these disorders may be treated with drugs known as chronobiotics, The pineal hormone, melatonin and the melatonin agonist, S20098, are examples of such drugs. In order to
New research has revealed that humans, in the course of their evolution, have conserved CNS mechanisms that can detect and respond to seasonal changes in daylength. In animals, such mechanisms modify the duration of nocturnal melatonin secretion which acts as a chemical signal that triggers profound seasonal change in behavior, such as those associated with breeding, hibernation and migration. The research shows that humans can also modify duration of nocturnal melatonin secretion in response to changes in daylength. Furthermore, there appear to be gender differences in the degree to which this response persists in modern urban settings. Women respond more than men. Although this difference could be invoked to explain the higher prevalence of seasonal affective disorder in women preliminary studies indicate that, on the contrary, melatonin response to seasonal changes in daylength are absent in women with SAD. The observation raises the possibility that the failure to respond to seasonal change is responsible for the emergence of depressive symptoms in winter in such individuals. Modem humans use artificial light to maintain a regime of long days and short' nights year-round. Results of experiments in which human have lived in short, winter-like days suggest that the modern use of artificial light has reduced sleep and eliminated rest. This change may lead to a state of chronic sleepiness in the general population and to disturbances in the timing and duration of sleep in individuals with bipolar illness and delayed sleep phase syndrome. In preliminary clinical experiments, individuals with each of these disorder has improved during imposition of a regime of "prehistoric" short days and long nights.
I8-18-41
DoesBright LightTreatment for Winter Depression Work Better Thana Placebo? c.I. Eastman, M.A. Young, L.F. Fogg. Biological Rhythms Research
Laboratory, Psychology Dept & Psychiatry Dept, Rush-Presbyterian-Sf Luke's Medical Centre, Chicago, IL, USA Artificial bright light is a popular treatment for seasonal affective disorder (SAD), and can reduce or eliminate the symptoms. However, there is a controversy about whether it is more effective than a placebo, because most previous studies did not use an appropriate placebo control treatment. We have devised a unique placebo control based on the suggestion that negative air ions may also be effective in the treatment of SAD. Deactivated negative ion generators were used for the placebo control. Patients could not tell if they were assigned to an active or de-activated generator group. This control treatment satisfies many criteria fOT a good control for treatment with a light box, such as requiring the same time investment, same change in sleep schedule, generating high expectations for benefits, and being inert. We also compared time of day of treatment: morning, after waking, and evening, before bed. All treatments were I 112 hrs in duration. This was a 5-week parallel design consisting of a baseline week and 4 treatment weeks. Patients were rated on the Hamilton depression scale and a supplemental "atypical" item scale for SAD at the end of each week. The study was planned to occur over 6 winters, in order to obtain a large enough sample size. Preliminary results (after the first 2 winters) have been presented (I). We will present the first analysis of the completed. 6-yr, study with an emphasis on whether bright light treatment was significantly better than placebo statistically, and if so, whether this difference is clinically important. [I] Eastman C I, Young M A, FoggL F.In: LightandBiological Rhythms in Man. Wetterberg L (ed), Pergamon Press.Oxford, 1993,371-383.
34 ical and psychological bases for these disturbances. We will distinguish between the most common presentations in the nursing home and in ambulatory settings and focus on the challenges that these disturbances present to the caregivers. Treatments for these conditions are varied and include environmental alternation, behavioral modification, re-direction and other pychotherapeutic techniques, background music, and bright lights. Further, we will describe the traditional and more recent pharmacotherapeutic interventions as well as the current and recent research that is being conducted in this area.
M. Van Der Linden. Abstract not available at time of publication.
Circadian Rhythms in Neuropsychiatry and Sleep Disorders
I8-18-1 I The Roleof the Suprachiasmatic Nuclei (SCN) as a Biological Clock: Effects of Melatoninergic Substances
F.w. Turek, O. Van Reeth. Centre for Circadian Biology & Medicine, Northwestern University Evanston, Illinois, USA It has clearly been established that the hypothalamic SCN contain an endogenous circadian pacemaker(s) that regulates most, if not all, 24-hr rhythms in mammals. One of the rhythms regulated by the SCN is the production and release of the hormone, melatonin, from the pineal gland: a rhythm in which melatonin levels are normally high during the night and low during the day. While the presence of the pineal gland is not necessary for the expression of other circadian rhythms, there is now substantial evidence from studies on rodents that treatment with melatonin, or melatonin agonists, can influence behavioural and metabolic rhythms under both free-running and entrained conditions. The recent finding that the SCN contains a high concentration of specific melatonin receptors, coupled with the observation that the direct application of melatonin-related compounds to the SCN in vitro can alter the rate of firing of SCN neurons, has led to the hypothesis that at least some of the effects of melatonin on circadian rhythmicity may be due to its feedback on the very clock regulating the rhythm of melatonin. Taken together with data on humans indicating that melatonin andJor melatoninergic substances, can modify the sleep-wake cycle as well as other circadian rhythms, the studies in rodents have led to a surge in interest in the possible use of melatonin-related drugs for the treatment of circadian rhythm abnormalities. Of particular interest is the possible use of such drugs in the elderly who show a pronounced reduced amplitude in the rhythm of melatonin in association with fragmented sleep-wake cycles, and disturbed circadian rhythmicity.
I8-18-21
18-18-31 Sleep and Mood Disorders: Relationship to Circadian Rhythms T.A. Wehr, E. Leibenluft, P.1. Schwartz, E.H. Turner, N.E. Rosenthal. NIMH, Besthesda, Maryland, USA
18-17-61
Is-181
examine these disorders and to investigate pharmacological treatments, a number of animal models have been developed using both nocturnal and diurnal rodents. These models will be described and the effects of both melatonin and S20098 reported. Other situations in which sleep patterns are disrupted such as in the elderly and during drug withdrawal will also be discussed.
Animal Models of Circadian Disorders andTheir Treatment with Chronobiotics
J.R. Redman. Department of Psychology, Monash University, Clayton, Australia Circadian disorders are characterised by abnormal timing of behaviours and physiological processes such as sleep and wakefulness, body temperature or plasma hormone levels. The DSM-IV now lists three types of sleep-wake schedule disorders in which there is a mismatch between the normal sleep-wake schedule and the person's environment. These are Advanced or Delayed type, Disorganised type, and Frequently Changing type. It has recently been reported that these disorders may be treated with drugs known as chronobiotics, The pineal hormone, melatonin and the melatonin agonist, S20098, are examples of such drugs. In order to
New research has revealed that humans, in the course of their evolution, have conserved CNS mechanisms that can detect and respond to seasonal changes in daylength. In animals, such mechanisms modify the duration of nocturnal melatonin secretion which acts as a chemical signal that triggers profound seasonal change in behavior, such as those associated with breeding, hibernation and migration. The research shows that humans can also modify duration of nocturnal melatonin secretion in response to changes in daylength. Furthermore, there appear to be gender differences in the degree to which this response persists in modern urban settings. Women respond more than men. Although this difference could be invoked to explain the higher prevalence of seasonal affective disorder in women preliminary studies indicate that, on the contrary, melatonin response to seasonal changes in daylength are absent in women with SAD. The observation raises the possibility that the failure to respond to seasonal change is responsible for the emergence of depressive symptoms in winter in such individuals. Modem humans use artificial light to maintain a regime of long days and short' nights year-round. Results of experiments in which human have lived in short, winter-like days suggest that the modern use of artificial light has reduced sleep and eliminated rest. This change may lead to a state of chronic sleepiness in the general population and to disturbances in the timing and duration of sleep in individuals with bipolar illness and delayed sleep phase syndrome. In preliminary clinical experiments, individuals with each of these disorder has improved during imposition of a regime of "prehistoric" short days and long nights.
I8-18-41
DoesBright LightTreatment for Winter Depression Work Better Thana Placebo? c.I. Eastman, M.A. Young, L.F. Fogg. Biological Rhythms Research
Laboratory, Psychology Dept & Psychiatry Dept, Rush-Presbyterian-Sf Luke's Medical Centre, Chicago, IL, USA Artificial bright light is a popular treatment for seasonal affective disorder (SAD), and can reduce or eliminate the symptoms. However, there is a controversy about whether it is more effective than a placebo, because most previous studies did not use an appropriate placebo control treatment. We have devised a unique placebo control based on the suggestion that negative air ions may also be effective in the treatment of SAD. Deactivated negative ion generators were used for the placebo control. Patients could not tell if they were assigned to an active or de-activated generator group. This control treatment satisfies many criteria fOT a good control for treatment with a light box, such as requiring the same time investment, same change in sleep schedule, generating high expectations for benefits, and being inert. We also compared time of day of treatment: morning, after waking, and evening, before bed. All treatments were I 112 hrs in duration. This was a 5-week parallel design consisting of a baseline week and 4 treatment weeks. Patients were rated on the Hamilton depression scale and a supplemental "atypical" item scale for SAD at the end of each week. The study was planned to occur over 6 winters, in order to obtain a large enough sample size. Preliminary results (after the first 2 winters) have been presented (I). We will present the first analysis of the completed. 6-yr, study with an emphasis on whether bright light treatment was significantly better than placebo statistically, and if so, whether this difference is clinically important. [I] Eastman C I, Young M A, FoggL F.In: LightandBiological Rhythms in Man. Wetterberg L (ed), Pergamon Press.Oxford, 1993,371-383.