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T A Wehr

Publications and source records attributed to T A Wehr.

At least 19 recordsLinked to original sources
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

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↗
PubMed1995

Suppression of men's responses to seasonal changes in day length by modern artificial lighting.

We recently reported that humans have conserved mechanisms, like those that exist in other animals, which detect changes in day length and make corresponding adjustments in the duration of nocturnal periods of secretion of melatonin and of other functions. We detected these responses in individuals who were exposed to artificial "days" of different durations. The purpose of the present study was to determine whether men who are exposed to natural and artificial light in an urban environment at 39 degrees N are still able to detect and respond to seasonal changes in duration of the natural photoperiod. We measured profiles of circadian rhythms during 24-h periods of constant darkness (< 1 lx) and found no summer-winter differences in durations of nocturnal periods of active secretion of melatonin, rising levels of cortisol, high levels of thyrotropin, and low levels of rectal temperature. The results of this and our previous study suggest that modern men's use of artificial light suppresses responses to seasonal changes in the natural photoperiod that might otherwise occur at this latitude.

Adaptation, Physiological↗
PubMed1994

Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM density and spontaneous awakening.

The sleep patterns of 8 normal subjects living in a winter-type photoperiod (10 h light and 14 h darkness; LD 10:14) for 4 weeks were characterized by the presence of periods of spontaneous wakefulness alternating with periods of spontaneous sleep. Transitions from sleep to wakefulness occurred much more frequently out of REM sleep than out of NREM sleep (P < 0.002). REM periods that terminated in wakefulness showed shorter REM durations (P < 0.0005) and higher REM densities (P < 0.0005) than REM periods that did not terminate in wakefulness. The authors discuss these results in terms of a possible relationship between REM density and arousal level. The higher REM density preceding wakefulness and the increased number of REM periods terminating in spontaneous awakenings could reflect an enhanced level of a brain arousing process, resulting from reduced sleep pressure in the extended nights.

Adult↗
PubMed1994

Sleep in fall/winter seasonal affective disorder: effects of light and changing seasons.

Disturbances of sleep are a hallmark of seasonal affective disorders (SAD), as they are of other mood disorders. Fall/winter SAD patients most often report hypersomnia. Among responses of 293 SAD patients on a symptom questionnaire, complaints of winter hypersomnia (80%) greatly exceeded insomnia (10%), hypersomnia plus insomnia (5%), or no sleep difficulty (5%). Increased sleep length in fall/winter is not unique to SAD. Among 1571 individuals across four latitudes surveyed at random from the general population, winter sleep increases of < or = 2 hr/day relative to summer were reported by nearly half. However, hypersomnia had a low correlation (r = 0.29) with the total number of other SAD symptoms that were reported in this sample. Ten SAD patients kept daily sleep logs across 1 yr that showed increases in fall and winter (sleeping most in October; least in May) whose maximum averaged 2.7 hr per day more weekend sleep than in spring and summer. These winter increases might have been somewhat attenuated since most received light therapy during part of the winter. Nocturnal EEG recordings of depressed SAD patients in winter showed decreased sleep efficiency, decreased delta sleep percentage, and increased REM density (but normal REM latency) in comparison with recordings: (1) from themselves in summer; (2) from themselves after > or = 9 days of light therapy; or (3) from age- and gender-matched healthy controls. Thus, the extent of fall/winter oversleeping recorded by our SAD patients did not differ dramatically from that reported by the general population, but sleep complaints of our SAD patients have been accompanied by features of sleep architecture that are different from healthy controls and are reversed by summer or by bright-light therapy.

Adult↗
PubMed1994

A controlled trial of cyanocobalamin (vitamin B12) in the treatment of winter seasonal affective disorder.

To test the hypothesis that cyanocobalamin (vitamin B12) is an effective treatment for winter seasonal affective disorder (SAD). 2 weeks of double-blind placebo washout, followed by random assignment to parallel treatments for 2 weeks with cyanocobalamin vs. placebo. Observations were made during weekly outpatient visits. All subjects met criteria for SAD. 27 patients were studied. After the washout period, 14 were randomly assigned to 1.5 mg cyanocobalamin (3 x/day) and 13 remained on placebo on the same schedule. 29 item SIGH-SAD scores were used to determine antidepressant efficacy. No significant differences were found in the responses between the two groups. Cyanocobalamin does not appear to be an effective short-term treatment for depression in SAD patients. The usefulness as a treatment for SAD of the methylated form of Vitamin B12, which has been used extensively in related studies, remains to be explored.

Adult↗
PubMed1994

Findings from the Seasonal Pattern Assessment Questionnaire in patients with eating disorders and control subjects: effects of diagnosis and location.

We previously reported a high degree of seasonality as measured by the Seasonal Pattern Assessment Questionnaire (SPAQ) in 41 patients with eating disorders (ED) compared with control subjects and patients with five other affective spectrum disorders. To clarify the relationship of the specific ED diagnosis and latitude to seasonal variation in a larger sample, we administered the SPAQ to 159 women with ED as defined by DSM-III-R. Subtype diagnoses were as follows: bulimia nervosa (BN), n = 109; anorexia nervosa (AN), n = 30; BN+AN, n = 20. Patients were studied at three locations: National Institute of Mental Health (NIMH), n = 46; Medical University of South Carolina (MUSC), n = 53; University of Michigan (UM), n = 60. The control group comprised 50 female normal volunteers studied at NIMH. There was a statistically significant difference in Global Seasonality Scale (GSS) scores among the four diagnostic groups, and all ED subtypes had significantly higher GSS scores than control subjects after post hoc Bonferroni t tests. Higher GSS scores were also found in patients with BN+AN compared with patients with BN or AN alone. The patterns of change were similar to those observed in winter seasonal affective disorder (SAD). Thirteen percent of the total sample of ED patients met SPAQ criteria for winter SAD, with 2.5% each for summer SAD and subsyndromal SAD. UM BN patients (latitude 42 degrees N) had higher GSS scores and a higher prevalence of winter SAD than MUSC BN patients (latitude 33 degrees N), but this difference was not statistically significant. These data support the hypothesis that ED and SAD may involve similar pathophysiological mechanisms, possibly related to serotonin dysregulation.

Adolescent↗
PubMed1994

A controlled trial of levodopa plus carbidopa in the treatment of winter seasonal affective disorder: a test of the dopamine hypothesis.

The objectives of this study were to test the hypothesis that a dopaminergic deficiency plays a role in the pathogenesis of winter seasonal affective disorder (SAD) and to test the efficacy of levodopa plus carbidopa as a treatment for SAD. Two weeks of double-blind placebo washout were followed by random assignment to parallel treatments for 2 weeks with levodopa and carbidopa versus placebo. Observations were made during weekly outpatient visits. All subjects met criteria for SAD. Fifty patients entered the study. Twenty-four were significantly depressed after the washout period and were randomly assigned to medication or placebo. Twenty-three completed the study. Twelve patients received placebo capsules four times a day during the 2-week drug comparison period. On an identical schedule, 11 patients received capsules containing levodopa (up to 7 mg/kg per day by the end of the second week) and carbidopa (100 mg/day). Twenty-one item Hamilton Rating Scale for Depression scores were used to determine antidepressant efficacy. No differences were found in the rates of response. There is no evidence to support the use of levodopa for the treatment of SAD patients in general. A model of systemic dopaminergic deficiency does not readily explain the pathology of SAD.

Adult↗
PubMed1993

Diurnal variations of serotonin and dopamine levels in discrete brain regions of Syrian hamsters and their modification by chronic clorgyline treatment.

In Syrian hamsters, chronic administration of the type A monoamine oxidase inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the circadian rhythm of wheel running, and changes the intensity-response curve for phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also decreases hypothalamic and peritoneal temperatures, particularly during the rest phase of the activity-rest cycle. To help identify monoamines that may mediate CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal variation was detected in all regions in saline-treated animals; for DA, no diurnal variation was detected in any region. In all regions, 5-HT levels and, to a lesser extent, DA levels were higher after CLG treatment. The acrophase of the 5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment, while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial preoptic area, and median raphe nuclei was no longer detectable after chronic CLG-treatment. The phase-delay induced by CLG treatment in the daily rhythm of serotonin levels in the SCN, which functions as a circadian pacemaker, may be an important mechanism underlying the drug's capacity to slow the intrinsic rhythm of the pacemaker and to phase-delay behavioral rhythms that are under its control.

Animals↗
PubMed1993

Conservation of photoperiod-responsive mechanisms in humans.

In animals, circadian pacemakers respond to seasonal changes in day length by making corresponding adjustments in the durations of diurnal and nocturnal periods of circadian rhythms; these adjustments mediate effects of photoperiod on breeding and other seasonally recurring phenomena. Little is known about photoperiod responses of human circadian pacemakers. To investigate this question, we recorded and compared circadian rhythm profiles of 15 individuals after chronic exposures to short (8 h) and long (14 h) nights. As occurs in animals, durations of nocturnal periods of active melatonin secretion (11.9 +/- 1.6 vs. 10.3 +/- 1.3 h, df = 14, t = 4.583, P < 0.0005, paired t test), high prolactin secretion (12.9 +/- 2.1 vs. 9.9 +/- 2.2 h, df = 11, t = 2.917, P < 0.01), and sleep (10.6 +/- 0.8 vs. 7.6 +/- 0.4 h, df = 14, t = 17.122, P < 0.0005) were longer after exposure to long nights than after short ones. Durations of nocturnal periods of low rectal temperature (11.6 +/- 2.3 vs. 9.5 +/- 1.6 h, df = 12, t = 3.912, P < 0.001) and rising cortisol secretion (10.8 +/- 1.6 vs. 9.3 +/- 1.9 h, df = 14, t = 3.130, P < 0.005) were also longer. Some of these differences persisted during 24-h periods of enforced wakefulness in constant dim light, indicating that prior exposure to the two regimes induced abiding changes in the timing of internal processes, such as circadian pacemaker oscillations, that control the durations of nocturnal and diurnal periods of the rhythms.

Adult↗
PubMed1992

Fluoxetine decreases brain temperature and REM sleep in Syrian hamsters.

The antidepressant drug, fluoxetine (FLX), a selective serotonin reuptake inhibitor, was administered to Syrian hamsters, and its acute and chronic effects on EEG sleep and hypothalamic temperature were recorded. Acute fluoxetine treatment at doses of 5, 10, 20 and 40 mg/kg decreased REM sleep and hypothalamic temperature in a dose-dependent manner. It increased NREM sleep, and, at doses of 20 and 40 mg/kg, it increased wakefulness. At 40 mg/kg, it decreased motor activity. During chronic treatment, tolerance developed to FLX's REM sleep-inhibiting effects, but tolerance did not develop to FLX's hypothalamic temperature-decreasing effects. Chronic FLX treatment produced circadian phase-dependent decreases in temperature beyond those that were observed during acute treatment. The apparent dissociation during chronic treatment between FLX's temperature-lowering effects and its REM-decreasing effects might be related to long-term changes in 5HT receptor function or FLX pharmacokinetics.

Animals↗
PubMed1992

Diurnal variation: reliability of measurement and relationship to typical and atypical symptoms of depression.

We used three rating scales to study diurnal variation of mood in 37 patients with major depressive disorder (17 drug-free patients and 20 treatment refractory patients on stable regimens of antidepressant medication). The three rating scales included global self-ratings administered twice a day; an itemized, prospective, observer-rated scale administered twice a day; and the retrospective item on the Hamilton Depression Rating Scale. Z scores and Intraclass Correlation Coefficients demonstrated a poor level of agreement between the itemized, prospective scale and the self-ratings. In addition, stepwise multiple regression analysis and point bi-serial correlation showed no systematic relationship between atypical diurnal variation (i.e., mood worsening in the evening) and atypical depressive symptoms (weight gain, hypersomnia, etc.), or between typical diurnal variation (i.e., mood worsening in the morning) and typical depressive symptoms (weight loss, insomnia, etc.). This lack of relationship was observed in both drug-free and medicated patients using each of the three rating scales. We discuss possible explanations for these negative findings.

Adult↗
PubMed1992

A brain-warming function for REM sleep.

During REM sleep, arterial blood flow, neuronal firing rates, metabolism, and temperature increase in many parts of the CNS. Eye muscle tone also increases, and the eyes exhibit bursts of rapid movements. If one of the functions of sleep is to conserve energy, then it is curious that energy is so conspicuously expended in the vicinity of the CNS during REM sleep. The author hypothesizes that homeotherms use REM sleep to produce heat in order to maintain a high, stable temperature in a restricted CNS core during sleep. The fact that several of the active features of REM sleep heat the CNS, and the fact that REM sleep propensity increases when core temperature physiologically decreases, seem consistent with the hypothesis that REM sleep is a regulated mechanism for warming the CNS.

Animals↗
PubMed1992

Is sleep deprivation useful in the treatment of depression?

OBJECTIVE: The authors critically reviewed the literature on clinical applications of sleep deprivation in the treatment of depression. DATA COLLECTION: They included all studies using sleep deprivation for clinical purposes, with the exception of treatment studies that did not provide follow-up beyond a night of recovery sleep. They focused on six uses of sleep deprivation: 1) to potentiate response to antidepressant medication (13 studies), 2) to hasten the onset of action of antidepressant medication or lithium (five studies), 3) to prevent recurrent mood cycles (four studies), 4) as an alternative to antidepressant medication (five studies), 5) as a diagnostic probe (two studies), and 6) to predict response to antidepressant medication (nine studies). FINDINGS: Although the literature appears to demonstrate the efficacy of sleep deprivation as a potentiation strategy, these treatment studies have substantial methodological shortcomings. Well-designed pilot studies indicate that sleep deprivation may hasten the onset of action of thymoleptic medications. Sleep deprivation may prevent premenstrual mood swings, and response to sleep deprivation may differentiate depressive pseudodementia from primary degenerative dementia with depression. Studies attempting to use sleep deprivation to predict response to antidepressant medication have yielded inconsistent results. CONCLUSIONS: Given the noninvasive nature of sleep deprivation, it would be useful to determine if even a small subset of refractory patients respond to it. The authors suggest future research directions to determine the usefulness of this potential treatment.

Depressive Disorder↗