Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism

Round 1

Reviewer 1 Report

Effect of gestational diabetes on postpartum depression and its mechanism

Thank you for the opportunity to review this paper. The authors present a study exploring the effects of GDM on postpartum depression using a rat model. The results suggest disruption of the Trp pathway and change in composition of the gut microbiota provide a putative physiological basis for increased postpartum depression in GDM.

Some parts of the manuscript require more references to support statements made (see comments). More measured language is called for including caution with use of the word ‘proof’, ‘proven’ etc. However, the methods and analysis appear to be sound, and the findings are very interesting and relevant.

With some minor edits, the paper is suitable for publication in Nutrients and will be of interest to clinician scientists exploring the relationship between GDM and postpartum depression.

Abstract

Line 19 change ‘not’ to ‘non’

Line 21 change ‘during lactation period’ to ‘during the lactation period’. And add the word ‘was’ after PPD

Line 35 I suggest instead of ‘worked as a physiological basis’ say ‘provide a putative physiological basis’

Introduction

The purpose and background are well described and justified. Although the risks are somewhat over-stated and more measured language is needed. More references are needed to support some of the statements.

Line 45 suggest remove the word ‘normal’. Instead of ‘prevents the mother from breastfeeding’ better to say ‘can interfere with breastfeeding’ as many mothers with GDM breastfeed successfully.

Line 46-47 I suggest remove the word ‘high’.

Lines 44-50. There needs to be references to support these statements.

Line 70. Remove ‘on people’

Line 72-79. These sentences need to be re-worked.

Line 81 remove ‘the infection of social’ and replace with ‘confounding by social’

Materials and methods

The materials and methods are well described and appear appropriate for the hypotheses tested.

Line 114. Exchange not for non

Line 115 exchange exceed for exceeding

Results

In some places exact p values are given and in others they are given as (>0.05). In my view it is better to state the agreed level of significance for the analysis in the methods section and them simply describe values as not significant. If a p value is mentioned I would prefer to see the value.

Line 353 exchange ‘than’ for ‘compared to’.

Line 355 After ‘Similarly trend’ put ‘Similarly, a trend’

Discussion

Here again more measured language is needed and statements (eg the first sentence) need to be referenced.

I suggest exchanging the words ‘proved’ and ‘proven’ at lines 443 and 436 for ‘indicated’ and ‘demonstrated’ given that one study is not enough to definitively prove a thing.

Lines 440-442 this sentence is unclear.

Line 448. Exchange ‘had a’ for ‘may have’

Line 458. Instead of ‘…dams, through negative feedback…’ try ‘…dams, which through negative feedback…’

Lines 463-465 This sentence needs re-phrasing.

Line 469. Instead of ‘By studying with the TPH2…’ say ‘In a study involving TPH2…’

Line477 Exchange ‘proved’ for ‘illustrated’

Line 481 put ‘but’ before other.

Line 481 change differ to differed.

Line 448. This statement needs to be referenced.

Lines 493-485. This is unclear. Perhaps say ‘The migration of the Trp pathway from 5-HT to Kyn may be one of the mechanisms inducing depressive-like behaviour in postpartum mothers with GDM.’

Line 514-517 shorten this sentence.

Lines 518-523. Statements need to be referenced.

Line 525. Try ‘In agreement with (reference) our study has demonstrated that GDM can induce an inflammatory state thereby increasing immune factors involved in the overexpression of IDO.

Line 528 exchange proved for ‘shown’

Line 550 add the word ‘the’ before ‘human’

Conclusions

The second sentence is too long. May be better broken into two.

Line 571 exchange ‘new idea’ for ‘novel putative

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

This article explores a major theme in the field of perinatal psychiatry, which is that of the links between the various physiological events inherent in the state of pregnancy, such as the modifications of glycemic regulation, and the intensity of postnatal maternal emotional dysregulation.
However, this article cannot be published in its present form and requires extensive revision.

title:
It is not about depression but about depressive like attitudes and it is necessary to specify that the study is done in rats and not in humans.

Introduction
The introduction on PND is simplistic and the links made between depression and breastfeeding or care difficulties concern animal data: it would be simpler to stick to animal data, and not to make the link with maternal PND right away, for example at the end of the discussion.

The objectives are very broad and the authors go a bit too far in their conclusions and assertions: the overall approach should be moderated

English should be reviewed.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Overall comments:

Thank you for the opportunity to review this article, which presents some really interesting findings on the association between GDM and PPD and elucidates the potential mechanism using a rat model. The authors have done well to explain the very technical mechanisms in the manuscript. However, the manuscript needs to be revised for language throughout. This would help to streamline the article and help the reader to understand the background and interpret the findings (see more specific comments on language below).

Specific comments:

Language

I would suggest that the authors review the manuscript for English language and grammar. This would help with the flow in reading the article, for example in line 20, I would suggest rephrasing to: “Fasting plasma glucose (FPG), cortisol (COR) and serotonin (5-hydroxytryptamine, 5-HT) metabolism were continuously monitored during THE lactation period until postnatal day.” Similarly, in the following sentence, PPD should be singular, so I would rephrase to: “PPD WAS evaluated by [several] behavioral tests.” I have used square brackets for several, as perhaps deleting this would be preferable as “several” is very vague and therefore does not really add value to the sentence. Careful review of the language should be done before this article is considered for publication.

Abstract

- Line 19: I would suggest changing the names of the study groups if possible to: blood glucose not recovered group (GH group) and blood glucose recovered group (GL group).

Introduction

- Line 44-46: I would suggest rephrasing this sentence, as it gives quite bold statements about the effects of PPD that should be more nuanced. Perhaps something like the following would be preferable: “PPD directly affects the mother’s mental health and social adaptability, and also interferes with her ability to adequately breastfeed and care for her child”.

Methods

- The methods are well explained and, besides a language review, I have no specific comments

Results

- The results are clearly presented visually by the bar charts and, for the most part, are well explained with some language edits required. However there is a lot of information presented and the results are very long which can make it hard to follow the findings and interpret the results overall. I would suggest maybe moving some of the less critical information to Supplementary material and making some of the text more concise so that the reader is able to better follow and interpret the key findings and pathways. For example, figure 10 a-e are quite difficult to see clearly and this makes it hard to interpret what is presented. I would suggest a review of the results section and potentially refining what is presented in figures/tables and then adjusting the text to reflect the results, but ensuring that you focus on key findings presented concisely without repetition.

Discussion

- As with the rest of the manuscript, the language should be revised in the discussion section. The authors should also be careful about their interpretation of findings and the conclusions drawn; for example, saying that results have “proved” a certain relationship (line 433) may not be appropriate as, while I think the behavioural findings support the presence of PPD symptoms in the rat model, I don’t think you can say that this is “proven”. Similarly with the following sentence, I don’t think it is appropriate to say that the result “proves that GDM can increase the risk of postpartum depression-like behavior”; while this is suggested from the findings of this study in the rat model, I think that saying this is a “proven” effect.

- Otherwise the discussion of the complex mechanisms is useful, just some general language editing would make this easier to follow. Have there been any relevant studies looking at hormonal/gut microbiota responses to GDM and any links to PPD. While these animal models are interesting and useful in elucidating causal pathways, it would be helpful to understand how this fits into and current/emerging work in humans.   

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors partially addressed comments about the links between depression in humans and their work exploring depressive attitudes in rats. In particular, the discussion of direct links between their results and causal inferences between blood glucose levels in pregnant women and PND should be tempered: their results are in animals and open to work in women.

Author Response

General Comments: The authors partially addressed comments about the links between depression in humans and their work exploring depressive attitudes in rats. In particular, the discussion of direct links between their results and causal inferences between blood glucose levels in pregnant women and PND should be tempered: their results are in animals and open to work in women.

Response : We have rewritten the sentence in line 447-450, stressed that the results were in rats. And the last sentence in first paragraph of Conclusions was deleted.