Abstract
Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under “unmasked”, time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.
Highlights
Mood is influenced by a non-additive interaction between circadian phase and duration of awakening [1]
A significant main effect of menstrual phase was observed (x2 = 5.00, P = .025), with progesterone values significantly increased during luteal phase (LP) compared to follicular phase (FP) in both groups (Table 1)
For area under the curve (AUC), a significant group x menstrual phase interaction was observed (Table 3) (H1 = 4.811, P = .028), with decreased values observed within premenstrual dysphoric disorder (PMDD) women during LP compared to FP (P = .03, Wilcoxon test)
Summary
Mood is influenced by a non-additive interaction between circadian phase and duration of awakening [1]. A chronobiological basis of affective disorders was proposed, and dysregulated circadian rhythms in psychiatric disorders, including major depressive disorder (MDD), seasonal affective disorder (SAD), bipolar disorder, and schizophrenia were observed [2,3,4]. Clock gene abnormalities are implicated in bipolar disorder and schizophrenia [5,6]. Women are up to twice as likely as men to suffer from affective disorders [8]. This raises the question of whether a circadian and menstrual interaction influences mood in women, and whether altered circadian rhythms contribute to the development of premenstrual dysphoric disorder (PMDD), a menstrual cycle-related mood disorder
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