Search PubMed⌕ Search

Biomedical subjects

T A Wehr

Publications and source records attributed to T A Wehr.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of seasonal changes in daylength on human neuroendocrine function.

The circadian pacemaker imposes stereotypic patterns of daily variation on the activity of human neuroendocrine systems. In a number of cases, these patterns exhibit waveforms that are characterized by distinct diurnal and nocturnal periods with relatively discrete transitions between them (corresponding to a biological day, a biological dusk, a biological night, and a biological dawn). In humans, for example, diurnal periods of absence of melatonin secretion, low prolactin secretion, and falling levels of cortisol alternate with nocturnal periods of active melatonin secretion, high prolactin secretion and rising levels of cortisol. In response to light, the circadian pacemaker synchronizes the timing of the biological day and night so that their timing and duration are appropriately matched with the timing and duration of the solar day and night. As the pacemaker carries out this function, it is able to adjust the duration of the biological day and night to match seasonal variation in the duration of the solar day and night. Thus, after humans have been chronically exposed to long nights (scotoperiods), the duration of nocturnal periods of active melatonin secretion, high prolactin secretion and rising levels of cortisol is longer than it is after they have been chronically exposed to short nights. Furthermore, the sleep-related peak of growth hormone secretion is half as high after exposure to long nights as it is after exposure to short nights. These responses to seasonal changes in duration of the natural scotoperiod are suppressed in most individuals - especially men - who live in modern urban environments in which they are exposed to artificial light after dark and artificial darkness during the daytime.

Animals↗
PubMed1998

Decreased sensitivity to light of the photic entrainment pathway during chronic clorgyline and lithium treatments.

Certain antidepressant drugs (ADs) cause disturbances in sleep that could result from their capacity to alter the timing of circadian rhythms. Effects on the timing of rhythms could be due to the drugs' known capacity to alter the frequency of the intrinsic rhythm of the circadian pacemaker, or to a capacity to modify the pacemaker's response to external stimuli that serve as time cues (Zeitgebers) that regulate the timing (phase) of its rhythm. To examine the possibility that ADs alter the sensitivity of the system that mediates the phase-shifting effects of light, hamsters were treated chronically with the MAOI, clorgyline, and lithium. Each hamster was then exposed to a single 5-min light pulse (intensity range = 0.00137 to 137 microW/cm2) at circadian phases known to elicit phase advances (CT18) and phase delays (CT13.5) in the daily onset of wheel running. The half-saturation constant (sigma), photic sensitivity (1/sigma), and maximum phase-shifting response to light were estimated from the best-fit stimulus response curves. In addition, threshold sensitivity, the light intensity required to produce a threshold phase-shifting response, was determined. Clorgyline decreased the magnitude of light-induced phase advances at each of the light intensities tested. Clorgyline also decreased the magnitude of light-induced phase delays at low light intensities, but increased the magnitude of phase delays at higher light intensities. Clorgyline decreased the sensitivity of the photic phase-shifting system, as indicated both by the threshold sensitivities at CT13.5 and CT18, and by 1/sigma at CT13.5. Lithium decreased the threshold sensitivity at CT18, and 1/sigma at CT13.5. Lithium decreased the magnitude of phase delays, but not phase advances. Clorgyline's effects on the photic entrainment pathway may be mediated by its effects on serotonin, which has been shown to modulate the pacemaker's response to morning and evening light, and by tolerance to this effect of serotonin. The fact that both clorgyline and lithium decrease the photic sensitivity of the entrainment pathway suggests that other psychoactive drugs might also share this property. It is possible that the decreased sensitivity to light of the entrainment pathway affects the clinical response to these and other psychoactive medications.

Adaptation, Physiological↗
PubMed1997

Dynamics of the human EEG during prolonged wakefulness: evidence for frequency-specific circadian and homeostatic influences.

The electroencephalogram (EEG) of nine healthy individuals was recorded at half-hourly intervals during approximately 40 h of sustained wakefulness in a constant routine protocol. EEG power density in the 0.75-9.0 Hz range exhibited a global increasing trend, and a local trough in the evening, centered approximately 6 h prior to the temperature minimum. The former could be attributed to a wake-dependent influence, and the latter to a circadian influence. Power density in the 9.25-12.0 Hz band showed a circadian modulation, the trough coinciding with the minimum of the endogenous rhythm of body temperature, whereas a wake-dependent influence was not evident. Power density in the 12.25-25.0 Hz range exhibited a wake-dependent increase, whereas a circadian modulation was absent. It is concluded that the circadian pacemaker and the wake-dependent (i.e. homeostatic) process affect the waking EEG in a frequency-specific manner.

Adult↗
PubMed1997

Increase of 5HT and VIP immunoreactivity within the hamster (Mesocricetus auratus) SCN during chronic MAOI treatment.

The effects of chronic treatment with the monoamine oxidase inhibitor (MAOI), clorgyline (CLG; 2 mg/kg per day) on serotonin (5HT) and vasoactive intestinal peptide (VIP) immunoreactivity (IR) within the hamster suprachiasmatic nucleus (SCN) were examined. Optical densities of 5HT IR and VIP IR were increased by MAOI treatment. VIP IR was increased in both the ventrolateral and dorsal regions of the SCN, suggesting that VIP content was increased within both perikarya and terminals of VIP neurons. The results suggest that previously described effects of MAOIs on the mammalian circadian system may be mediated in part, by their effects on serotonergic input to VIP neurons within the SCN.

Animals↗
PubMed1997

Seasonal variation in core temperature regulation during sleep in patients with winter seasonal affective disorder.

Nocturnal core temperature during sleep is elevated during depression compared with remission in nonseasonally depressed patients. Similarly, nocturnal core temperature is higher during winter depression compared with remission induced by light treatment in seasonal affective disorder (SAD) patients. We investigated whether nocturnal core temperature in SAD patients naturally becomes lower in summer (during remission) compared with winter (during depression). Twenty-four-hour core temperature profiles were obtained in winter and summer in 22 SAD patients and 22 controls. The nocturnal core temperature minima were lower in summer compared with winter in SAD patients (p < .005), but not controls (p > .4). The seasonal changes in nocturnal core temperatures in SAD patients may reflect a unique physiological responsiveness of SAD patients to the change of seasons, and may be intimately related to the seasonal disturbances of mood and energy that are characteristic of SAD.

Adult↗
PubMed1997

Seasonality and pituitary volume.

Pituitary volume in humans has been reported to change size in response to experimental manipulations of photoperiod, and to be increased during an episode of non-seasonal major depression. We wanted to determine whether pituitary volume changes either across the seasons or during an episode of winter depression. Nineteen patients with winter-seasonal affective disorder and 19 sex-, age-, height-, and weight-matched controls underwent magnetic resonance imaging of the pituitary gland in both winter and summer. Images were obtained using 0.7-mm contiguous slices and the areas of all slices were summed to compute the final volume for each gland. We found no main effects or interactions involving either diagnosis or season in our primary analysis. In a post-hoc analysis, we found a trend towards a season x gender effect (P = 0.06), such that pituitary volume increased slightly (+4.0%) across seasons in women, whereas it decreased slightly (-4.3%) across seasons in men. The results suggest that neither winter depression nor the change of seasons is associated with a significant change in pituitary size.

Age Factors↗
PubMed1997

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms.

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.

Adrenocorticotropic Hormone↗
PubMed1997

Restoration of detectable melatonin after entrainment to a 24-hour schedule in a 'free-running' man.

We evaluated a 37-year-old male with a non-24-h sleep-wake disorder. His environment gave him little exposure to bright light. Circadian profiles of temperature, melatonin, thyrotropin, cortisol and testosterone were obtained along with endocrine challenges of the thyroid, adrenal, growth hormone and gonadal axes. Multiple endocrine abnormalities were detected. Testosterone was low and nocturnal thyrotropin levels were erratic. Serum melatonin was undetectable throughout the day and night on multiple occasions, and responses to infusions of TRH, GnRH and GRF-44 were abnormal. Responses to CRH infusion were normal. The patient was successfully entrained to a 24-h schedule by daily exposure to 2500 lux light from 0700h to 0900h, avoidance of light (by wearing dark goggles) from 1800h to 2300h, and strict enforcement of a dark environment from 2300h to 0700h. After entrainment, a normal pattern of nocturnal melatonin secretion was found. GH response to GRF-44 also normalized, although abnormal responses to TRH and GnRH persisted. This case raises the possibility that a complex interaction of light exposure with the circadian system can reversibly suspend pineal gland secretion of melatonin indefinitely. It also suggests that circadian rhythm disorders be considered in the differential diagnosis of abnormal endocrine function.

Adult↗
PubMed1997

Melatonin and seasonal rhythms.

The pineal hormone melatonin plays a ubiquitous role in biology as a chemical mediator of the effects of season on animal physiology and behavior. Seasonal changes in night length (scotoperiod) induce parallel changes in the duration of melatonin secretion (which occurs exclusively at night), so that it is longer in winter and shorter in summer. These changes in duration of nocturnal melatonin secretion, in turn, trigger seasonal changes in behavior. The retinohypothalamic-pineal (RHP) axis's responses to light are highly conserved in humans. Like other animals, humans secrete melatonin exclusively at night, and they interrupt its secretion when they are exposed to light during the nocturnal period of its secretion. In many individuals, the RHP axis also is capable of detecting changes in the length of the night and making proportional adjustments in the duration of nocturnal melatonin secretion, producing the type of melatonin message that animals use to trigger seasonal changes in their behavior. This has been shown both in naturalistic studies in which melatonin profiles were compared in summer and winter and in experimental studies in which melatonin profiles were compared after chronic exposure to long and short artificial "nights." Individuals who live in modern urban environments differ in the degree to which, or even whether, the intrinsic duration of melatonin secretion (the duration measured in constant dim light) responds to seasonal changes in the length of the solar night. Changes in the intrinsic duration of melatonin secretion that are induced by changes in the scotoperiod are highly correlated with changes in the intrinsic timing of the morning offset of secretion and are only weakly correlated with changes in the intrinsic timing of evening onset of secretion. This finding suggests that differences in the way in which individuals are exposed to, or process, morning light may explain differences in their responsiveness to changes in duration of natural and experimental scotoperiods. Although the human RHP axis clearly is capable of detecting changes in the length of the night and in producing the melatonin message that other animals use to trigger seasonal changes in their behavior, it is not yet known whether or how the human reproductive system or other systems respond to this message.

Animals↗
PubMed1997

Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men.

The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men.

Adolescent↗
PubMed1997

Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder.

BACKGROUND: The ready availability of exogenous melatonin means that its use in patients with mood disorders is probably not uncommon. Nonetheless, few controlled trials of exogenous melatonin in these patients have been conducted. METHOD: Five patients with rapid-cycling DSM-III-R bipolar disorder were treated with melatonin 10 mg q.d. at 10:00 p.m. for 12 weeks. Melatonin was added to a stable regimen of medication and administered in a double-blind, placebo-controlled fashion. RESULTS: Melantonin administration had no positive effects. One patient developed a free-running (unentrained) sleep-wake cycle after melatonin withdrawal. In addition, in both this and a second patient, there is evidence that the administration of exogenous melatonin may have suppressed the secretion of endogenous melatonin. CONCLUSION: The administration of melatonin had no significant effects on mood or sleep. However, melatonin withdrawal delayed sleep onset time and may have had some mild mood-elevating effects.

Affect↗
PubMed1996

Salivary and plasma measures of dim light melatonin onset (DLMO) in patients with rapid cycling bipolar disorder.

A number of researchers have suggested that the phase (timing) of circadian rhythms in depressed patients is abnormal. Longitudinal studies could help to elucidate the relationship between circadian phase and mood. Such studies would be facilitated by the development of a noninvasive method for measuring circadian phase. In normal volunteers, the concentration of salivary melatonin measurements has been shown to be significantly correlated with those obtained in plasma; however, it is unknown whether salivary melatonin measurements can reliably detect the unmasked time of onset of nocturnal melatonin secretion (a measure of circadian phase). In addition, the relationship between salivary and plasma melatonin measurements in medicated psychiatric patients is unknown. We measured plasma and salivary melatonin simultaneously in a sample of 12 medicated patients with rapid cycling bipolar disorder. The intraclass correlation coefficient between plasma and salivary measures of the dim light melatonin onset (DLMO) was 0.93. We therefore conclude that salivary melatonin can be used to determine the time of the DLMO in this population.

Adult↗
PubMed1996

Relationship between sleep and mood in patients with rapid-cycling bipolar disorder.

The relationship between sleep and mood was examined in a longitudinal, naturalistic data set derived from out-patients with rapid-cycling bipolar disorder. Eleven patients completed daily self-ratings of mood and sleep logs for 18 months. Using logistic regression with autoregressive terms, we examined the effect of prior sleep (sleep duration, time of sleep onset, and time of wake onset) on the probability of being in a depressed, manic, or hypomanic episode on one or more subsequent days. Of the three sleep parameters, decreased sleep duration was the best predictor of mania or hypomania the next day, followed by wake onset time. The association between sleep duration and subsequent mood was less consistent for depression than for mania or hypomania. Four of the patients showed no relationship between mood and any of the sleep variables measured. These results reinforce the importance of monitoring, and perhaps controlling, sleep duration and wake onset time in at least some patients with rapid-cycling bipolar disorder.

Adult↗
PubMed1996

Winter seasonal affective disorder: a follow-up study of the first 59 patients of the National Institute of Mental Health Seasonal Studies Program.

OBJECTIVE: The purpose of this study was to characterize the long-term course of patients with seasonal affective disorder. METHOD: The first 59 patients with winter seasonal affective disorder who had entered winter protocols were retrospectively followed up after a mean interval of 8.8 years. Detailed life charts were constructed through use of a semistructured interview and collateral records. RESULTS: The disorder of 25 patients (42%) remained purely seasonal, with regular recurrences of winter depression and no depression or treatment through any summer. The course of illness was complicated by varying degrees of nonseasonal depression in 26 patients (44%). The disorders of eight patients (14%) had fully remitted. Certain features of the group with complicated seasonal affective disorder suggested that they were more severely ill. Twenty-four patients (41%) continued to use light treatment regularly throughout the follow-up period. Light treatment was preferred to medication for winter recurrences, although antidepressants had been used in the winter by most (63%) of the patients who still used lights at follow-up. CONCLUSIONS: The pattern of winter depressions and summer remissions remained fairly persistent over time in this group of patients. The temporal distribution of depressive episodes both within and across individual patients was consistent with the results of several recent follow-up studies of seasonal affective disorder, providing support for the predictive and construct validity of the Rosenthal et al. diagnosis of winter seasonal affective disorder. Light treatment, while remaining a safe and satisfactory treatment for many, may be insufficient for more severely ill patients. The appearance of nonseasonal depressions in patients with winter seasonal affective disorder may be associated with greater severity of illness and less responsiveness to light treatment.

Antidepressive Agents↗
PubMed1995

Bimodal patterns of human melatonin secretion consistent with a two-oscillator model of regulation.

In many animals, changes in duration of nocturnal melatonin secretion chemically mediate effects of seasonal changes in nightlength on behavior and physiology. According to one model, the changes in duration of secretion result from adjustments in the timing of two circadian oscillators, one entrained to dusk, controlling onset, and another entrained to dawn, controlling offset. Consistent with this model, in six women, we found separate and reproducible evening and morning peaks of melatonin secretion that might represent the separate expressions of rhythms of two oscillators.

Adult↗
PubMed1995

Serotonin and thermoregulation. Physiologic and pharmacologic aspects of control revealed by intravenous m-CPP in normal human subjects.

Meta-chlorophenylpiperazine (m-CPP), a probe of central serotonergic function, elevates core temperature in rodents, nonhuman primates, and humans via serotonin receptor-mediated mechanisms. To further characterize the thermoregulatory aspects of this response, we studied 16 healthy volunteers using multiple core and skin temperature recording sites. Compared to placebo, intravenous m-CPP (0.08 mg/kg) produced statistically significant biphasic changes in rectal temperature, characterized by initial hypothermia (-0.04 degrees C at 12 minutes) followed by progressive hyperthermia (+0.17 degrees C at 90 minutes). m-CPP also produced significant increases in plasma norepinephrine concentrations. Analysis of the skin temperature recordings suggests that the effector mechanism primarily responsible for m-CPP-induced core hyperthermia is increased metabolic thermogenesis. Individual differences in the magnitude of the hyperthermia were independent of m-CPP plasma concentrations but were found to be linearly correlated with the level of the previous night's core rectal temperature minimum and mean. It appears that m-CPP activates a mode of metabolic thermogenesis governed by a nocturnally sensitive proportional control mechanism. The operation of such a proportional controller is characterized by a set point and a gain, and has been implicated in the general economy of mammalian energy balance.

Adult↗
PubMed1995

Antidepressant drug-induced hypothalamic cooling in Syrian hamsters.

Antidepressant drugs have been reported to alter the circadian pattern of body temperature, but specific effects on the amplitude or on average body temperature are not consistent, and there have been no specific studies to examine chronic drug effects on brain temperature. To address these issues, hypothalamic temperature (Thy) was monitored telemetrically in hamsters treated with three antidepressant drugs: the monoamine oxidase inhibitor (MAOI), clorgyline; the 5HT reuptake inhibitor, fluoxetine; and the alkali metal, lithium. For comparison, hamsters were also treated with two neuroleptic drugs, chlorpromazine and haloperidol. Each of the three antidepressant drugs, but neither of the neuroleptic drugs, produced a chronic decrease in diurnal (rest-phase) hypothalamic temperature. The Thy-decreasing effect of clorgyline was not prevented by pinealectomy, and Thy decreased more than peritoneal temperature (Tp), thus reducing the temperature difference between the hypothalamus and the peritoneal cavity. Less general effects of the antidepressants were also observed. Clorgyline and fluoxetine, but not lithium, delayed the 24-hour rhythm of Thy. Clorgyline and lithium, but not fluoxetine decreased the average 24-hour Thy. The neuroleptics chlorpromazine and haloperidol decreased the amplitude of the 24-hour Thy rhythm. The fact that chronic antidepressant drugs, but not neuroleptic drugs, decrease Thy is consistent with their different neurotransmitter effects and clinical applications, and raises the possibility that their antidepressant property might be related to their capacity to decrease Thy during sleep.

Animals↗