Title: Menstrual cycle related depressive symptoms and their diurnal fluctuations – an
ambulatory assessment study
Version: 3 Date: 27 Aug 2024
Reviewer:  Margot W L Morssinkhof
Reviewer's report:
Summary
The authors have conducted an interesting and impressive study, collecting data on reported
depressive symptoms 3 times a day for a full menstrual cycle. The study methods are thorough
and explained well, and the statistical analyses match the research question well. The authors
studied menstrual cycle-dependent variations in diurnal symptom variations as well as menstrual
cycle-dependent symptom severity, and find that some participant clearly display cycle-related
variations in symptom severity.
I think the authors have collected an impressive amount of intensive data, and they have analysed
it well, but I do think there is more potential in this paper, especially concerning the translation
from fundamental statistical findings towards clinical relevance.
Recommendations
Below, I have listed my point-by-point recommendations for the paper.
1. I would recommend that the authors maybe reorder their study aims to align with the order
they are introduced with in the title and abstract: first, studying menstrual cycle-related symptom
variance and second, studying diurnal fluctuations in this variance. This way, the cycle-related
variation is more central in the paper and the diurnal fluctuations are a refined assessment of
the cycle-related variance – which aligns better with the introduction and discussion as written
by the authors.
2. I would also recommend that the authors use very consistent key terms to describe these two
phenomena (i.e., cycle-related symptom severity and cycle-related diurnal variation?). Although
the manuscript is written well and clearly, I could have used two key terms which are defined
and introduced and then used consistently to remind me which aspect of symptom variation is
being described in every part of the paper.
3. One of the major assumptions made in this paper is that menstrual cycle-related changes
would follow a cosine pattern. Can the authors show the raw data in a spaghetti plot, to show that
the symptoms follow this pattern and not another pattern which would fit better? Furthermore,
could the authors also discuss why a cosine pattern would fit better than, for example, a cycle-
dependent categorical pattern with the follicular and early luteal phase as non-symptomatic
phases and the late luteal phase as severely symptomatic, which is the assumed pattern of
PMDD? This topic could also be discussed more in the introduction and discussion.
4. One of my bigger points is that the authors introduce the clinical relevance by mentioning
PMDD and PME, including mentions of prevalence rates, but they do not study possible
prevalence of PME or PMDD-like trajectories in this manuscript. I believe that based on the
unique data in the manuscript, including within-person tracking of symptoms using a clinical
scale, the authors could actually make an estimate of how many participants show PMDD-
or PME-like trajectories, for example by using the absolute averaged scores and comparing
symptom severity between the different standardized cycle phases. This could be included as a
third study aim, and I think it would greatly increase the clinical relevance of the paper.
5. In the same line, I wonder whether there are cycle- or phase-dependent changes in how many
women meet the PHQ-9 cutoff for depression. How many participants are below the PHQ-9
cutoff for depression in the follicular and early luteal phase, but above the cutoff in the late
luteal phase?
6. Looking at figure 2, I think it would be helpful to darken the zero/null line so that the figure
more clearly shows which symptoms show the strongest cyclicity. I would also recommend
adding a y axis label, to remind readers what the figure shows.
Altogether, the manuscript is well-written and shows a unique set of data! The analyses have
been done well and the results fairly display the data, but I believe that the authors could also
use the data to gain some clinically relevant insights into PMDD or PME. I wish the authors
the best of luck with this project.
I would recommend the editor to accept this paper pending major revisions.