Seasonal mood change and neuroticism: the same construct?

The personality trait of neuroticism has been found to be associated with a polymorphism in the regulatory region of the serotonin (5-HT) transporter gene (5-HTTLPR). This same genetic polymorphism has also been associated with seasonal changes in mood and behavior, or seasonality. The purpose of the current study was to determine whether seasonality and neuroticism are actually the same construct given that they are both associated with the same genetic polymorphism. We administered the Seasonal Pattern Assessment Questionnaire (SPAQ), which measures the severity of seasonality, and the Revised NEO Personality Inventory (NEO-PI-R), which measures the severity of neuroticism, to 45 subjects diagnosed with seasonal affective disorder (SAD). SAD is a clinical expression of seasonality in which patients develop a major depressive disorder in the winter that remits in the summer and can be treated with light therapy. No significant correlation was found between neuroticism and seasonality. We conclude that seasonality and neuroticism are not the same construct, even though the 5-HTTLPR polymorphism is a genetic risk factor for each.

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder.

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.

Discrepancy between in vitro and in vivo antifungal activity of albendazole.

Albendazole has in vitro activity against Cryptococcus neoformans and reduced in vitro activity for albendazole when compared with Candida albicans. The major metabolite of albendazole, albendazole sulphoxide showed no in vitro activity against isolates of either fungus. Immunocompetent mice infected intravenously (i.v.) with C. albicans were treated with albendazole doses of 20-600 mg kg-1 per day in noble agar or sesame oil for per oral (PO) administration, or 80 mg kg-1 per day in DMSO for intraperitoneal (i.p.) and i.v. administration for 10 days, and were observed for survival. Mice infected with C. neoformans intracranially received albendazole in daily doses of 600 mg kg-1 prepared in DMSO (i.p.) or peanut butter/rat chow (PO) for 10 days and were observed for survival. Mortality was not different between the treated and control animals in any study. Plasma samples from uninfected mice dosed with similar formulations and doses of albendazole were analysed by HPLC for albendazole and albendazole sulphoxide. No albendazole could be detected in any sample, while concentrations of albendazole sulphoxide (286-8697 ng ml-1) were observed in all samples. These data suggest that the absence of in vivo activity for albendazole is due to rapid conversion to the inactive albendazole sulphoxide metabolite.

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.

Nutritional parameters observed during 28-day infusion of recombinant human tumor necrosis factor-alpha.

In conjunction with a Phase I investigation of the antineoplastic activity of recombinant human tumor necrosis factor-alpha (TNF-alpha), administered as a 28-day continuous infusion, selected nutritional parameters were evaluated to identify any effect that might be attributed to the TNF infusion. Seven clinically stable men with a variety of tumor types were studied. None had clinical or laboratory evidence of significant malnutrition before entry into the study. Five patients received 10 micrograms of recombinant human TNF-alpha per square meter per day and two patients received 25 micrograms/m2 per day. Indirect calorimetry assessment of resting energy expenditure, body weight, serum TNF concentration, and laboratory analysis of common nutritional markers (albumin, prealbumin, and triglycerides) were performed at baseline, day 14, day 28, and 2 weeks (day 42) after completion of the infusion. There were no statistically significant differences by analysis of variance observed in any parameter during the study period compared with baseline values and values on day 42. Also, there were no differences between any parameters when stratified by dose administered, although the number of patients studied was small. Measured serum TNF concentrations ranged from 0.02 to 1.56 ng/mL and did not correlate with study day or dose of TNF infused. No correlation was observed between serum TNF concentrations and resting energy expenditure. Although others have reported significant metabolic changes associated with acute administration of TNF in humans and animals, our experience does not support a hypermetabolic state in patients receiving low daily dose, long-term (28-day) continuous infusion of recombinant human TNF-alpha, a state that may be consistent with many neoplastic conditions.

High-dose itraconazole in the treatment of severe mycoses.

Eight patients with systemic mycoses and with prior treatment failures were treated with itraconazole (600 mg/day) for a mean duration of 5.5 months. All six patients without AIDS experienced improvement or stabilization of their fungal infections while receiving high-dose itraconazole, although two patients later experienced treatment failures, one by relapse and one by progression, on lower doses. Treatment failures also occurred in the two patients with AIDS and cryptococcal meningitis. The failures were associated with low serum itraconazole concentrations (less than 2.5 micrograms/ml) in both patients. All other patients had mean trough levels in serum above 5 micrograms/ml. One patient who was improving on 600 mg/day developed a progressive infection after reduction of the dose to 400 mg/day. Side effects included reversible adrenal insufficiency in one patient; severe hypokalemia, mild diastolic hypertension, and rhabdomyolysis in one patient; mild hypokalemia and hypertension in four other patients; and breast tenderness in one patient. The mean decrease in serum potassium during treatment was statistically significant (P = 0.05). Selected patients with severe systemic mycoses may benefit from prolonged high-dose itraconazole treatment. However, 600 mg/day may be approaching the upper limits of acceptable dosing for long-term treatment.

Core body temperature in patients with seasonal affective disorder and normal controls in summer and winter.

The rationale for phototherapy in seasonal affective disorder (SAD) was originally based on the notion that SAD patients were light deprived during the wintertime and needed more light. We previously found normal temperature profiles of untreated SAD patients during the winter, and that phototherapy significantly enhanced the amplitude of the circadian temperature profile in SAD patients during the winter (Rosenthal et al 1990). We hypothesized that summer would act similarly on the temperature rhythm of these patients. In this study we examined the temperature data from SAD patients and normal controls during the summer and compared it to the results of our previous study. We found identical profiles for SAD patients and normal controls during the summer and that summer significantly lowered the overall temperature profiles of both groups and did not alter the amplitudes. These results raise questions about the validity of the current theories of the mechanism of light therapy.

Effects of light treatment on core body temperature in seasonal affective disorder.

Abnormalities in circadian rhythms of core body temperature have been reported previously in depressed patients. In this study, we compared the temperature rhythms of 10 depressed seasonal affective disorder (SAD) patients with winter depression with those of 12 normal controls and evaluated the effects of bright light on temperature in SAD. Unlike previous studies of depressed patients, the temperature curves of the patients and normal controls during the off-light condition were nearly identical. We found a significant difference in amplitude between the patients in the untreated and light-treated conditions. Although there was no systematic difference in circadian phase across groups or treatment conditions, we present preliminary evidence that suggests that phase-typed subgroups may be present in the population distinguished by their treatment responses.