Ana M. López

Relationship of morningness-eveningness questionnaire score to melatonin and sleep timing, body mass index and atypical depressive symptoms in peri- and post-menopausal women.

Previous work shows a relationship between measures of morning or evening preference (e.g., morningness-eveningness questionnaire (MEQ) scores) and melatonin and sleep timing, body mass index (BMI) and mood. This study explores the relationship of these factors to atypical depression (ATD) symptoms, particularly increased appetite and hypersomnia, in depressed and non-depressed peri- and post-menopausal women. Participants were 19 normal control subjects and 10 depressed patients, 46-72 years of age. In a university hospital setting, we administered the MEQ and Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD version), which includes a measure of ATD, 3-5 weeks before obtaining nighttime polysomnography and overnight plasma melatonin in dim light (<30lx). Scores on SIGH-SAD appetite-related items were significantly correlated with MEQ, dim light melatonin onset (DLMO) time and midsleep time (MST); BMI was related to MST, sleep end time, phase-angle differences between sleep and melatonin timing, and appetite measures. Results suggest that relative to women with earlier DLMOs and MSTs, depressed peri- and post-menopausal women whose DLMOs and MSTs are phase-delayed may experience increases in appetite, hypersomnia, and BMI. These symptoms might be relieved by sleep or light manipulations that advance melatonin and sleep timing parameters.

Antepartum depression severity is increased during seasonally longer nights: Relationship to melatonin and cortisol timing and quantity

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than their nondepressed counterparts to phase alterations in melatonin and cortisol timing during seasonally longer nights. Interventions that phase delay melatonin and/or cortisol timing—for example, increased exposure to bright evening light—might serve as an effective intervention for antepartum depressions whose severity is increased during seasonally longer nights.

Reduced Phase-Advance of Plasma Melatonin after Bright Morning Light in the Luteal, but not Follicular, Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study

The authors previously observed blunted phase-shift responses to morning bright light in women with premenstrual dysphoric disorder (PMDD). The aim of this study was to determine if these findings could be replicated using a higher-intensity, shorter-duration light pulse and to compare these results with the effects of an evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to 10:00 h in dim (<30 lux) or dark conditions the night before (Night 1) and after (Night 3) a bright-light pulse (administered on Night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3000 lux for 6 h or 6000 lux for 3 h) was given either in the morning (AM light), 7 h after the dim light melatonin onset (DLMO) measured the previous month, or in the evening (PM light), 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak, or area under the curve. These findings replicated the authors’ previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal-phase subsensitivity or an increased resistance to morning bright-light cues that are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD. (Author correspondence: bparry@ucsd.edu)

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.

The relationship of nocturnal melatonin to estradiol and progesterone in depressed and healthy pregnant women.

PURPOSE To assess the relationship between nocturnal plasma melatonin and serum estradiol (E(2)) and progesterone (P(4)) levels in depressed pregnant women (DW) and matched healthy women (HW). METHODS We used analysis of variance (ANOVA) and linear regression analyses on data obtained from pregnant HW and DW. RESULTS Log E(2) and log P(4) were positively correlated with measures of melatonin quantity in HW (p<0.05) but not DW, controlling for age. Log E(2) and log P(4) were positively correlated with melatonin offset and duration in DW (p<0.01) but not HW. CONCLUSIONS Pregnant DW may be less sensitive than HW to modulation of melatonin secretion by E(2) and P(4). That melatonin timing measures are more sensitive to E(2) and P(4) variation in DW may reflect a circadian system more attuned to the need for realignment in DW than in HW. These altered sensitivities to reproductive hormones may reflect a biologic vulnerability that predisposes some pregnant women to depression.

Premenstrual Dysphoric Disorder and Postpartum Major Depression: Chronobiology

Investigators have proposed many theories for the pathogenesis of premenstrual and postpartum depression. Evidence for chronobiological theories shows that disturbances in the timing (phase) or amplitude of circadian rhythms contribute to the symptoms manifested in these disorders related to women’s reproductive cycle. Relevant circadian rhythms include sleep, melatonin, cortisol, thyroid hormones, and prolactin (PRL). Diurnal patterns of secretion of these hormones in relation to sleep and to the changing reproductive hormones of each epoch are described. Disturbances in melatonin and PRL characterize premenstrual depressive disorders, whereas disturbances in sleep are common in postpartum depressive disorders.

Neuroendocrine Correlates of Sleep in Premenstrual, Pregnant, Postpartum and Menopausal Depression

To compare groups of normal control (NC) women with depressed patients (DP) diagnosed with Premenstrual Dysphoric Disorder (PMDD) or major depressive episode (MDE) during pregnancy, postpartum, peri- or postmenopause, with respect to neuroendocrine correlates of sleep architecture. We hypothesized that NC and DP would differ in the pattern of relationships between neuroendocrine and sleep measures across reproductively related depressions