Susana Feldman-Naim

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.

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.

Agreement between face-to-face and telephone-administered mood ratings in patients with rapid cycling bipolar disorder

We examined the reliability and level of agreement between the telephone and face-to-face administration of two mood-rating scales (HIGH-SAD and SIGH-SAD) in patients with rapid cycling bipolar disorder (RCBD). Two clinicians administered the HIGH-SAD and SIGH-SAD to 14 outpatients with RCBD. Patients received consecutive phone and face-to-face mood ratings in a randomized order. Using a paired t-test, no significant differences were found when comparing HIGH-SAD and SIGH-SAD scores administered face-to-face and over the phone. There was a high correlation between the face-to-face and phone administration of both scales as measured by intraclass correlation (r = 0.94 for SIGH-SAD; r = 0.85 for HIGH-SAD). Our results support the use of phone-administered mood ratings as a reliable and convenient method to monitor patients with RCBD.

Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with Seasonal Affective Disorder

A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale—Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not dem-onstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine2 receptor downregulation and dopamine agonism.

Gender differences in glycosylated hemoglobin levels in seasonal affective disorder patients and controls.

Seasonal affective disorder (SAD) has been shown to manifest different symptoms in female and male patients. Specifically, women with SAD have been shown to have greater increases in overeating, weight gain, and increased sleep as compared with their male counterparts. Given these dietary changes, we predicted that female SAD patients would exhibit increased glycosylated hemoglobin (HbA1) levels, indicative of chronically elevated glucose levels. Twenty-two patients (15 women and seven men) and matched controls were enrolled during the winter season and tested for HbA1 levels. A three-way analysis of variance (ANOVA; gender x group x season) was insignificant and the result was a negative study. After the initial hypothesis was rejected, we undertook a post-hoc analysis of the data, from which emerged that in winter, women patients had higher HbA1 levels as compared with matched controls. As our original hypothesis was rejected, we cannot accept the results of the post-hoc study. However, numerous other studies have demonstrated that female and male SAD patients differ in their pathophysiology, and are suggestive that in future analyses ought to consider analyzing subjects separately across gender.

Validation of the hypomania interview guide-seasonal affective disorder (HIGH-SAD) version in patients with rapid cycling bipolar disorder.

We validated the Hypomania Interview Guide‐Seasonal Affective Disorder (HIGH‐SAD) version in patients with rapid cycling bipolar disorder (RCBD). Fourteen outpatients were rated on six separate occasions (total= 84 visits). On each visit the patients were rated with the HIGH‐SAD and the Young Mania Rating Scale (YMRS) in a counterbalanced order. Clinical assessment was completed at the end of the visit by the treating psychiatrist. Patients were assessed as hypomanic/manic on 22 of the visits. Pearson correlation coefficient between the YMRS total scores and the HIGH‐SAD total scores for those 22 visits in which patients were hypomanic/manic was r= 0.629 (P< 0.05) and for all visits was r= 0.769 (P<0.0001). Analysis with only one rating per patient yielded a Pearson correlation coefficient of r=0.792 (P<0.0004). We found that the HIGH‐SAD was a valid scale for the measurement of hypomania in patients with RCBD. However, the scale does not differentiate hypomania from mania in this group of patients. Depression and Anxiety 8:166–168, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.