Methods for REM Sleep Density Analysis: A Scoping Review

Round 1

Reviewer 1 Report

Comments for author File: Comments.pdf

Author Response

REVIEWER #1

• Comment 1: Few articles focus on the systematics of REM density and its assessment. The authors take the task to systematically investigate REM density in patients with affective disorders and conclude that there is no clear definition and consensus of how to score REM density in the international literature. The AASM guidelines seem to be the most appropriate so far. It is certainly a benefit to have this review to initiate the consensus process.
  • Answer: We appreciate the Reviewer’s positive comments about our scoping review. We agree that a consensus or some other official position on the topic by AASM or other stakeholder in Sleep Medicine is necessary, and we are glad we can help on raising this need.

• Comment 2: Why do they select affective disorders without including bipolar disorder and mania in their search?
  • Answer: The present study is a secondary investigation of another systematic review, which was intended to evaluate by means of a meta-analysis the effect of depressive symptoms in REM sleep density. As we were performing it, it became clear that there were no standards for the quantification of REM sleep density. Therefore, we decided to derivate this scoping review from the previous (and still ongoing) meta-analysis. We acknowledge that REM sleep density is not exclusively related to depression, being also evaluated under the scope of other mood disorders (bipolar disorder and mania included) and even other mental health conditions (such as schizophrenia). In any case, these facts are not likely to influence the results reached by this scoping review due to 2 main reasons: 1. Depression is the condition most closely related to REM sleep density alterations, at least in number of articles published. 2. We believe that the same inconsistencies on the methods used to quantify REM sleep density would have been achieved, even if our search were broader to encompass bipolar disorder and other conditions. In any case, we have enlarged the discussion about this topic, discussing it as a limitation in the discussion section.

Discussion, p. 10: “As a limitation of our study, it shall be mentioned that this is a secondary analysis of a systematic review of REM sleep density alterations in individuals with depressive symptoms. We acknowledge that REM sleep density is not exclusively related to depression, being also evaluated under the scope of other mood disorders (bipolar disorder and mania included) and even other mental health conditions (such as schizophrenia). Although this scoping review was based on studies specifically about depression, we believe this is not likely to influence the results or decrease the reliability of these findings, due to 2 main reasons First, depression is the condition most closely related to REM sleep density alterations. Second, we believe that the same inconsistencies on the methods used to quantify REM sleep density would have been achieved, even if our search were broader to encompass bipolar disorder and other conditions.”

• Comment 3: Why are they not relating their selection of affective disorders to their methodological findings more detailed in the article?
  • Answer: While the data collection for this scoping review was restricted to studies about depression (as being secondary to another meta-analyses, as previously mentioned), we do not believe the results of it are in any case restricted to depression. In other words, we believe that our results are extensible to any case in which REM sleep density is evaluated. In any case, the restrictions to studies related to depression are made clearer in the revised manuscript, especially in the limitations paragraph, discussed int the comment above.

• Comment 4: They cite the metaanalyses of Baglioni (although meta analyses had been excluded) who has been exploring REM features in different psychiatric disorders, but do not refer to the lack of definition of REM density in this article.
  • Answer: Although the meta-analyses published by Baglioni et al. (2016) has been cited in the introduction and discussion sections, it was used only to provide supportive information for the relationship between REM sleep density and mental disorders (rather than to say the definition of REM sleep density is lacking). This meta-analysis was not retrieved on our systematic review (as it does not meet our inclusion criteria, as correctly pointed out by the Reviewer) and its data have not been used for any of the analyses we performed. For the sake of clarity, the studies used in our analyses are those listed in Table 1. In any case, we have reviewed all cases in which this meta-analysis is cited, to assure it is used accordingly.

• Comment 5: REM density definition is essential for all kind of studies in all kind of diseases and disorders, ie narcolepsy and RBD. This should be highlighted in the discussion.
  • Answer: We agree that analyzing REM sleep density might be important for other condition beyond mood disorders. This is now presented and discussed in the discussion section, as suggested.

Discussion – p.10: “We acknowledge that REM sleep density is not exclusively related to depression, and evaluating it may be relevant under the scope of other mood disorders (bipolar disorder and mania included), other mental health conditions (such as schizophrenia), and sleep disorders involving REM sleep alterations (such as narcolepsy and REM sleep behavioral disorder).”

We are grateful to the Reviewer for his/her careful reading and attention to our work. His/her suggestions were very relevant and improved our manuscript. We hope with these corrections and enhancements this manuscript can be considered suitable for publication in Clocks & Sleep.

Author Response File: Author Response.pdf

Reviewer 2 Report

The premise of this scoping review was to evaluate for consistency in the measurement of REM density, one of the parameters used to evaluate for psychopathologies such as depression. This was a well conducted review and thorough discussion describing the variability in measurements. The conclusion that a consistent measurement tool and guideline are needed is warranted.

This is relevant to determine validity and reliability of measuring density as one of the parameters used to evaluate for psychopathologies such as depression. This review is novel in addressing this gap in the literature.

Since different measures are used to evaluate REM density and there is inconsistency in instruments and their inter-measurement reliability, this review enhances knowledge and identifies the need to conduct further research to fill this gap.

As a scoping review, no improvements were identified. Controls would not be relevant.

Conclusions are consistent with the evidence. Limitations notes were accurate and appropriate. The authors addressed the main question.

References are appropriate and up to date.

The tables and figures are appropriate and enhance the manuscript.

Is there consistency in the measurement of REM density across studies?

Author Response

REVIEWER #2

• Comment 1: The premise of this scoping review was to evaluate for consistency in the measurement of REM density, one of the parameters used to evaluate for psychopathologies such as depression. This was a well conducted review and thorough discussion describing the variability in measurements. The conclusion that a consistent measurement tool and guideline are needed is warranted. This is relevant to determine validity and reliability of measuring density as one of the parameters used to evaluate for psychopathologies such as depression. This review is novel in addressing this gap in the literature. Since different measures are used to evaluate REM density and there is inconsistency in instruments and their inter-measurement reliability, this review enhances knowledge and identifies the need to conduct further research to fill this gap. As a scoping review, no improvements were identified. Controls would not be relevant. Conclusions are consistent with the evidence. Limitations notes were accurate and appropriate. The authors addressed the main question. References are appropriate and up to date. The tables and figures are appropriate and enhance the manuscript.
  • Answer: We appreciate the Reviewer’s positive comments about our scoping review and the results we have reached.

• Comment 2: Is there consistency in the measurement of REM density across studies?
  • Answer: Considering consistency on the parameters being used to measure REM sleep density, our evidence indicates that the methodologies applied differ greatly among the studies. In other words, this indicates that there are no specific REM sleep density methods being used consistently among the articles. Considering consistency on the results reached by different REM sleep density methods, our methodological approach is not able to solve this issue, but we plan to evaluate that on further studies. This issue is now reinforced in the discussion section.

Discussion, p. 9: “By the current results, we are not able to estimate the level of discrepancies among the different REM sleep density calculation methods. It is very likely that different methods would lead to different estimates even when applied to the same PSG recording. However, neither the magnitude of this discrepancy nor how much one method under or overestimate REM sleep density over another can be determined by our methodological approach. We also cannot determine which is the best method for calculating REM sleep density. Solving these issues would require analyzing polysomnographic data from a clinically characterized sample and evaluating the accuracy of different methods to estimate REM sleep density on predicting specific outcomes.”

We would like to thank the Reviewer for the time spent evaluating this manuscript. We have considered all comments and suggestions and hope this revised version can be considered eligible for publication in Clocks & Sleep.

Author Response File: Author Response.pdf