Changes in melatonin synthesis parameters after carbon monoxide concentration increase in the cavernous sinus.

Previous studies indicate that the gaseous messenger carbon monoxide (CO) is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight. This study was designed to determine whether the increased concentration of CO in ophthalmic venous blood affects the synthesis of melatonin and therefore, whether CO released from the eye under normal lighting conditions can be a carrier of light intensity information. Thirty six mature male wild boar and pig crossbreeds (n = 36) were studied. We measured the difference in the scotophase melatonin pathway response in terms of mean concentration of increased melatonin levels after 48 hours infusion of autologous blood plasma with an experimentally induced approximately 3-fold increase in the concentration of CO into the ophthalmic venous sinus. We demonstrated in this crossbreed a marked variation in the duration and amplitude of nocturnal melatonin peak in response to increased concentration of CO in ophthalmic venous blood. During the winter this treatment limited the nocturnal melatonin rise. During the summer this same experimental treatment enhanced the nocturnal melatonin rise. Changes in melatonin levels were always associated with parallel changes in AANAT protein levels. This work demonstrates that non-physiological changes in CO concentration in ophthalmic venous blood can have an acute impact on the systemic melatonin level. These results support humoral phototransduction as a mechanism for some of bright light's effects in animal chronobiology and treatment of winter seasonal affective disorder.

Is seasonal affective disorder a disorder of circadian rhythms?

Seasonal affective disorder (SAD) is a form of depression that starts in the fall and ends in the spring. This article reviews existing theories about the relationship between circadian rhythms and the disorder. Recent research indicates that as with pharmacologic antidepressants, at least 2-4 weeks are needed to demonstrate the effectiveness of bright-light therapy compared to placebo. The response to such treatment is strongest with precisely timed light exposure: treatment is optimal during the morning hours when the circadian system is susceptible to phase advance. Such clinical improvement is correlated with the magnitude of the phase shift induced. These observations suggest a model of circadian function in SAD and provide important guidelines for its treatment.

No effect of light on basal glucagon levels in winter seasonal depressives and comparison subjects.

We explored the effect of light therapy upon basal fasting plasma glucagon in 15 patients with winter depression vs. 15 comparison subjects before and after at least 1 week of light treatment. No differences were seen between groups or conditions. There was no correlation between glucagon change and antidepressant response.

Carbon monoxide poisoning and treatment with hyperbaric oxygen in the subacute phase.

The use of normobaric versus hyperbaric (>2 atm) oxygen in the treatment of carbon monoxide intoxication continues to be a matter of debate despite reports of increased efficacy with hyperbaric oxygen. When hyperbaric oxygen is used, immediate treatment is preferred for best results. The therapeutic window of time, however, is unknown. A patient presented with acute confusion and partial retrograde and total anterograde memory loss due to carbon monoxide poisoning. He was initially treated with normobaric oxygen and failed to show appreciable improvement. One month after carbon monoxide exposure the patient underwent treatment with hyperbaric oxygen and showed appreciable symptom relief confirmed by clinical findings and neuropsychological testing. This case shows that hyperbaric oxygen may be efficacious in the recovery of neuropsychiatric function up to 1 month after carbon monoxide induced brain injury.

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.

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.

Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder.

To determine whether circadian profiles of various plasma hormones are abnormal in patients with winter seasonal affective disorder (SAD), we obtained 24-hour profiles of plasma cortisol, prolactin, and thyrotropin in subsets of a sample of 22 depressed patients with SAD on and off light therapy and in subsets of a sample of 24 normal controls. Cortisol levels did not differ between patients and controls, and levels in patients were not affected by light therapy. Prolactin levels were lower in patients than in controls throughout the day (p < 0.03) but were unaffected by light therapy. Independent of patient vs. control status, prolactin levels were higher in women than in men throughout the day (p < 0.003). Thyrotropin levels were no different in patients and controls, but levels in patients were lower following light therapy (p < 0.05).

The phototherapy light visor: more to it than meets the eye.

OBJECTIVE: The purpose of the study was to ascertain whether phototherapy light visors provide an effective treatment for seasonal affective disorder. Previous studies have demonstrated a moderate response rate but have failed to find any difference in efficacy between light intensities. METHOD: Subjects were randomly assigned to receive, over a 2-week treatment period, 30 minutes of morning phototherapy with a light visor that emitted either a dim (30-lux) red light or a bright (600-lux) white light. Raters were blind to treatment, and patients were unaware of the alternatives. Response was assessed by using the structured 21-item Hamilton Depression Rating Scale, with an eight-item addendum for atypical depressive symptoms. Fifty-seven patients were enrolled across two sites. RESULTS: Patients assigned to the different visors had similar baseline depression scores and similar expectations of outcome. Hamilton depression scale scores declined by 34.6% for subjects given bright white light and by 40.9% for subjects given dim red light. Scores for atypical depressive symptoms fell by 44.1% for patients assigned the bright white light visors and by 49.0% for patients assigned the dim red light visors. Altogether, 39.3% of the patients who received red light and 41.4% of the patients who received bright white light showed a full clinical response. CONCLUSIONS: There were no significant differences in therapeutic response between patients who were treated with red or white light. The results of this study suggest that the phototherapy light visor may function as an elaborate placebo. Alternative explanations, however, are considered.

1,25 (OH)2 vitamin D3 levels in seasonal affective disorder: effects of light.

1,25 (OH)2 vitamin D3 levels were assessed in nine females and six males with winter seasonal affective disorder and in 15 age- and gender-matched controls in winter during periods with and without treatment with light therapy. No difference was found between groups or across conditions, though wide variations within each group make the presence of a type II error possible.

Platelet [3H]paroxetine binding, 5-HT-stimulated Ca2+ response, and 5-HT content in winter seasonal affective disorder.

The present study was designed to evaluate cellular serotonergic functions in winter seasonal affective disorder (SAD) using serotonin (5-HT)-stimulated Ca2+ response as an integrated measure of 5-HT2 receptor function in platelets, [3H]paroxetine binding to characterize the platelet 5-HT transporter and 5-HT content as an index of the platelet storage capacity for this neurotransmitter amine. Purified density-dependent subpopulations of platelets in untreated and light-treated SAD patients and matched controls were investigated in order to control for possible variations in platelet turnover. We found no differences between SAD patients and controls on any of the measures, nor between light therapy conditions in SAD patients, although we found a higher Bmax of [3H]paroxetine binding and 5-HT content in heavy platelets compared to light platelets. Although the validity of platelet serotonergic measures as a model for brain serotonergic systems still remains to be elucidated, we found no evidence of platelet serotonergic abnormalities in our sample of SAD patients.

Effects of light on T-cells in HIV-infected subjects are not dependent on history of seasonal affective disorder.

In order to evaluate the effect of light on helper- and suppressor-T-cell counts in HIV-infected individuals, with and without a history of seasonal affective disorder (SAD), we treated 35 subjects with 45 min of light therapy in the morning, in a crossover design involving two 2 week treatment conditions: visible white light (half-peak band width, 530-620 nm; 10,000 lux) and visible red light (half-peak band width, 615-685 nm; 175 lux). We found small but significant differences between the two treatment conditions, with higher CD4 and CD8 levels during the white, as compared with the red, condition. There were no differences between baseline and treatment conditions. Both light treatment conditions were associated with significant mood improvements in the SAD, but not the non-SAD, subjects. There was no evidence that the higher cell counts seen under the bright light conditions were mediated by the effects of light on mood or on plasma cortisol levels. While the size of the light effect on T-cells renders questionable the potential therapeutic value of this treatment modality for HIV, the finding is of theoretical interest and is reassuring for those HIV-infected individuals who require light treatment for other reasons.

Effects of phototherapy on electrooculographic ratio in winter seasonal affective disorder.

Low electrooculographic (EOG) ratios have been reported in patients with seasonal affective disorder (SAD). This study was undertaken to replicate these results and to consider the effects of light therapy on the EOG in SAD patients. Sixteen outpatients with SAD and 16 age-, sex-, and medication-matched control subjects had EOG testing before and after 1 week of light therapy during the winter. The EOG ratios in the SAD patients were only marginally lower than those in the normal control subjects. These differences persisted after light therapy. Although the slightly decreased EOG ratios in SAD patients might have resulted from an artifact of test variability, drowsiness, or other confounding factors, the difference between patients and control subjects raises the possibility of retinal abnormality in SAD.

Side effects of light therapy in seasonal affective disorder.

The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used.

Spontaneous eye blink rate in winter seasonal affective disorder.

We investigated spontaneous eye-blink rates in 19 drug-free patients with winter seasonal affective disorder (SAD) and 18 normal control subjects. At baseline, there were no significant differences between the two groups (mean +/- SD blink rate: 15/minute +/- 8 vs. 15/minute +/- 7). Light therapy (10,000 lux: 1 hour each morning for 1 week) produced no significant change in mean (+/- SD) blink rates either in 10 SAD patients (13/minute +/- 8 vs. 10/minute +/- 7) or in 12 normal control subjects (15/minute +/- 6 vs. 14/minute +/- 6). A post hoc exploratory analysis of the effect of light therapy on premenopausal female subjects (5 patients and 9 control subjects) showed a significant decrease in mean (+/- SD) blink rate in the patients after treatment (17 +/- 6 vs. 12 +/- 8 compared with 15 +/- 7 vs. 16 +/- 5). These results do not support the idea that an elevated blink rate may be a general biological marker in SAD, but they suggest a possible link between light treatment and mechanisms that regulate blink rate in premenopausal SAD patients.

A multicenter study of the light visor for seasonal affective disorder: no difference in efficacy found between two different intensities.

Fifty-five patients with winter seasonal affective disorder (SAD) were treated with a light visor, a newly developed portable light-delivery system, in a controlled parallel design. A dim (400 lux) visor was compared with a bright (6000 lux) visor for either 30 or 60 minutes in the morning for 1 week. Response rates for these two treatments were 36% and 56%, respectively; the duration of treatment sessions did not affect outcome. There was no evidence that the brighter visor was superior in efficacy to the dimmer one. Significantly greater relapse occurred following withdrawal of the dimmer visor. Alternative explanations for these findings are that the light visor is acting as a placebo or that it is equally effective over a wide range of intensities.

Light visor treatment for seasonal affective disorder: a multicenter study.

The effectiveness of light therapy in seasonal affective disorder (SAD) was evaluated in 105 subjects across five centers. Three intensities of light (60 lux, 600 lux, and 3500 lux) were used in a 2-week randomized, parallel design. There was no significant difference in antidepressant efficacy of the three intensities of light. All three intensities produced a similar frequency of antidepressant response to each other and to that reported in previous studies. There were site differences in the severity of depression during light treatment, but diagnosis and medication status did not affect antidepressant response. These findings suggest that light therapy has an antidepressant action by a nonspecific effect or that light is biologically active in the treatment of SAD across a wide range of intensities.