Alterations in the circadian control of melatonin secretion may be related to the development of mood disruption in women with premenstrual dysmorphic disorder (PMDD), according to the findings of a pilot clinical study.
Ari Shechter, PhD, from the Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Department of Psychiatry, McGill University in Montreal, Quebec, Canada, and colleagues published their findings online December 19 in PLoS One.
"In PMDD, it [has been] hypothesized that ovarian hormone variations may alter the expression of the endogenous circadian pacemaker and precipitate mood disruption in predisposed females," the authors write. "While chronobiological investigations in PMDD have been limited and inconsistent, [former researchers have] noted abnormal melatonin rhythm in PMDD, including phase-advanced offset, shorter duration of secretion, and decreased levels compared to controls."
The current study included 5 women with PMDD and 5 unaffected control women. The authors compared changes in hormone levels and mood between these 2 groups during two 24-hour periods in the follicular and luteal phases of the menstrual cycle. Women with PMDD had a significantly lower 24-hour melatonin area under the curve (AUC) during the luteal phase, when these women are symptomatic, than they did during the follicular phase, when symptoms have subsided (660.29 ± 132.44 vs 769.34 ± 142.33, respectively; P = .03).
Compared with women in the control group, women with PMDD had a lower 24-hour melatonin AUC during the luteal phase (660.29 ± 132.44 vs 984.66 ± 151.36). Similarly, the melatonin amplitude was significantly lower in the PMDD group during the luteal phase than in the control group (37.19 ± 9.01 pg/mL vs 61.37± 6.44 pg/mL; P = .05).
Mood was assessed, using an 11-item visual analogue scale (VAS), for the 4 core symptoms (depressed mood, tension, affective lability, and irritability) separately, and these 4 scores were then averaged together to create a measure of overall mood called VAS-core. Although there were no statistical differences between the groups in average age (30.4 vs 33.6 years), body mass index (23.5 vs 22.02 kg/m2), length of menstrual cycle (26.4 days for each group), or progesterone and estradiol levels in either the luteal or the follicular phases, women in the PMDD group had a significantly higher VAS-core score in the late luteal phase compared with women in the control group (47.00 ± 7.94 vs 5.57 ± 1.93; P ≤ .03). The mood of PMDD women also significantly worsened during the luteal phase of their cycles compared with the follicular phase of their own cycles (P ≤ .03).
Significant (P < .05) differences in nocturnal melatonin levels were observed in the women in PMDD group during both the follicular and luteal phases compared with women in the control group. "In the current study," the authors write, "nocturnal melatonin secretion in PMDD was reduced at both menstrual phases, compared to controls, which suggests a trait-vulnerability or a trait-marker for the disorder." Reduced nocturnal melatonin secretion may contribute to sleep disturbances (a symptom often reported by women with PMDD), they explain.
The authors included the small sample size and the potential for type 2 error resulting from insufficient power as study limitations.
"[W]e described abnormal circadian melatonin secretion, which may relate to a serotonergic dysfunction in PMDD women," the authors conclude. "Findings of this pilot study indicate that pharmacological approaches such as exogenous nocturnal melatonin supplements, melatonin receptor agonists, or agomelatine should be further tested as therapeutic approaches for the management of depressive symptoms, and encourage more work on the chronobiological basis of psychiatric disorders including PMDD."
Jacqueline A. Hart, MD, contributed to this article.
This study was supported by an operating grant from the Canadian Institutes of Health Research. One author was supported by a scholarship from the Fonds de la recherche en santé du Québec and is the founder and chief executive officer of Alpha Logik Consultants Inc. The other authors have disclosed no relevant financial relationships.
PLoS One. Published online December 19, 2012. Full text
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