The Interplay Between Suicidal Behavior and Mental Disorders: Focusing on the Role of Glial Cells

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

The authors have addressed all the comments thoughtfully and thoroughly, significantly improving the manuscript. Thank you for your careful revisions and dedication to strengthening your work — keep up the excellent efforts!

Author Response

Reviewer 1 evaluation:

Reviewer 1 Comments and Authors’ Responses:

 

Point 1:   The authors have addressed all the comments thoughtfully and thoroughly, significantly improving the manuscript. Thank you for your careful revisions and dedication to strengthening your work — keep up the excellent efforts!

Response 1: Thank you very much for your comments and efforts. Much appreciated.

Author Response File: Author Response.pdf

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

see pdf

Comments for author File: Comments.pdf

Comments on the Quality of English Language

revise

Author Response

Reviewer 2 evaluation:

Reviewer 2 Comments and Authors’ Responses:

The Interplay Between Suicidal Behavior and Mental Disorders: Focus on the Role of Glial Cells. This is an interes?ng review on a topic not widely developed in the scien?fic literature but of great interest. However, it lacks depth in the topic covered and is lost in collateral considera?ons. A complete revision of the review is needed.

Dear reviewer, thank you for your time and valuable comments. Much appreciated.

Point 1: Both the introduc?on and chapter 2 are extremely confusing, repe??ve, and do not address a clear need for this review. There are very good reviews on the essence of glial cells, their func?ons in the healthy brain, their physiological adap?ve responses, and their reac?ons in different pre-pathological and pathological scenarios. In the introduc?on, it would be enough to men?on their func?ons, and in chapter 2, glial responses in physiology and then in pathology in a generic way. I don't know why there is so much emphasis on pain (if it is important in suicidal behavior, it should be addressed later). Table 1 is meaningless. Glial cells are present in ALL regions of the CNS, and their dysfunc?on is present in ALL neurodegenera?ve diseases (not in 4) and in ALL (?) mental illnesses. It makes no sense to base the table on laboratory catalogs rather than on references for specific diseases.

Response 1: Thank you for this comment. The introduction and chapter one are now reassembled based on your suggestion. Table 1 is deleted.

Point 2: The key, in general terms and later analyzed in chapters 3 and 4, is to show glial reac?ons. Gliosis is an ambiguous term but highly indica?ve of important changes, ini?ally defensive and, if chronic, neurotoxic. Reac?ve changes (A1 and A2 as well as M1 and M2; pro-inflammatory and an?-inflammatory, respec?vely) are very important in the pathogene?c courses of brain diseases.

Response 2: The concept of gliosis was clarified in the text for astrogliosis and microgliosis as well.

 

 

 

 

 

 

 

Point 3: The important chapters are 3 and 4. Table 2 should be moved (a?er revision) to the beginning of chapter 3. Each subchapter could contain a table showing the findings in the brains and blood samples studied (morphological gliosis/non-gliosis - increase/decrease in glial elements-, pro-inflammatory and/or an?-inflammatory phenotypic changes). Fig. 2 is illustra?ve (it should indicate what MDD, SUD, etc. are) but it should perhaps be expanded with more detailed tables for each subchapter. Figure 3 is not well designed: e.g., neuronal degenera?on and glial dysfunc?on JOINTLY occur in neurodegenera?ve diseases. The genes are not solely glial, it is not indicated whether there is hyper- or hypo-gliosis/atrophy or only phenotypic changes, and which neuronal-neuroglial systems are affected. Table 2 is be?er specified but the references are poorly made (this table may be a summary of the tables I proposed above).

Response 3: Table 2 was moved to the beginning of chapter 3 as recommended by the reviewer. In this paper I was not planning to go this deep regarding all the findings maybe in the coming paper. In Fig. 2, changes are made in its caption for clarification. A simple change was made for fig. 3 that indicates that both neuronal degeneration and glial dysfunction jointly occur in ND. Arrows in fig. 3 is an indication of hypo-/hyper- expression of glial markers. References of Table 2 are fixed.

Point 4: Perhaps it would be interes?ng to add a chapter on treatments to prevent suicide, both in general and those dedicated to regula?ng glial dysfunc?ons.

Response 4: A small and brief chapter regarding the treatment is added based on your suggestion.

Point 5:  Other considera?ons: a) I consider Fig. 1 to be unnecessary: Furthermore, “loca?on” does not reflect reality (i.e., among synapses (?); most frequent in the white ma?er (there exists different subsets), the brain colored regions are not explained ......... b) “Glial cells exhibit mul?faceted func?ons and represent essen?al contributors to various physiological ... demonstrated by recent research” Many decades. C) “Those in the CNS (neocortex) are represented by three major lineages as follows: astroglia, microglia, oligodendrocytes and their progenitors NG2-glia” = Those in the CNS are represented by three major lineages as follows: astroglia, microglia and oligodendroglia (including the OL-progenitors or NG2 cells)

Response 5: a) A part of figure 1 was deleted; it is just an illustrative figure with direct information about the CNS glial cells for general knowledge. B) a part of this sentence is deleted. C) The sentence is changed based on your suggestion.

Point 6: This reviewer does not like the designa?on of neuroglial cells as non-electrical/non- neuronal cells, although he is aware of its use by some authors. Many astroglial cells have close rela?onships with the electrical currents of the circuits and have ion channels that facilitate them (Bhoi R, Mitra T, Tejaswi K, Manoj V, Ghatak S. Role of Ion Channels in Alzheimer's Disease Pathophysiology. J Membr Biol. 2025 Jun;258(3):187- 212. doi: 10.1007/s00232-025-00341-8). Astroglia and oligodendroglia are epithelial cells derived from glioblasts during development or in certain areas of the adult brain and microglia derive from mesodermal cells as well described by the author.

Response 6: Thank you for the comment. The idea of glial cells being non-electrical was removed although many papers include it. But I agree with the reviewer based on the findings in the article suggested above. The origin of glial cells is added as mentioned in this last sentence of this reviewer’s comment.

 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

I have reviewed the new version of this work with great interest and attention. I note that the chapters have been modified very much in line with my suggestions. I believe this version is very good and will be of great interest to both experts and readers eager to learn about this serious problem. As the author points out, further research into the topic is possible and necessary.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Journal: Neuroglia (ISSN 2571-6980)

Manuscript ID: neuroglia-3411770

Type: Review

Title: The Interplay between Suicidal Behavior and Mental Disorders: Focus on the Role of Glial Cells

 

This manuscript titled “The Interplay between Suicidal Behavior and Mental Disorders: Focus on the Role of Glial Cells” by Maya Nahi Abou Chahla, contributes significantly to the study of neuropsychiatry by emphasizing the crucial function of glial cells in SB and other mental illnesses. Its broad coverage, molecular depth, and diverse integration make it an important resource for both researchers and physicians. With small structural and clarity changes, it has the potential to significantly improve our knowledge and approach to SB.

 

Comments: Minor Revision

 

1.      Abstract: Phrases like "Glial cells have shown to possess vital and surprising roles" can be more comprehensive and scientific, as instead of ambiguous statements like "vital and surprising roles."

Introduction

2.      Establish a clearer link between glial cell dysfunction and SB early in the introduction.

3.      Include instances of psychiatric diseases to make the title more relevant.

Glial Cells Functions

4.      Explain the precise mechanisms and pathways involving glial cells in psychiatric illnesses and SB.

5.      Lines 134-150, 175-183, 229-256: Repeated concepts and terminology, such as the roles of microglia and astrocytes, might be simplified

 

6.      Lines 209–214: For clarification, briefly explain concepts like "primed microglia" and "kynurenine pathway".

7.      Lines 294–306, 325–334: Certain data points are confusing or contradicting. For example, in schizophrenia, microglial markers such as TREM2 and P2RY12 are said to be high (Line 297) but later found to be inconsistent due to comorbid variables (Lines 294-295). There are similar contradictions in the notion of BD and glial involvement in neuroinflammation.

       Address disparities explicitly, providing plausible explanations or possibilities.
       Following each paragraph, include a summary phrase that highlights the consensus and gaps in existing understanding.

 

  Lines 333–334, 328–329:

8.       Expand on the pathways that connect glial dysfunction to SB and mental diseases.
Provide further information about the therapeutic implications of these pathways.

 

 

Author Response

Please See the Attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The review is devoted to a relevant and interesting topic - the role of glial cells in the development of suicidal behavior. The manuscript is interesting but lacks quality due to many issues that I identified here below. The manuscript is written carelessly and perfunctorily. The  data is sometimes not sufficiently supported by references or not presented properly. Although appropriate, the manuscript needs editing to highlight the data presented and pass a clear message (writing is sometimes incomprehensible). It needs a clear description of the background, the problem and the existing data. The description of the role of glial cells in section 2.1. "Glial Cells Functions"  is extremely lightweight and formal. 

Additional comments:

The font size in Figure 1 is too small and the text is extremely difficult to read. The figure is not informative and does not contain any new information.

Line 56 - The author indicates that according to WHO, suicide is  leading cause of death in the world. This is incorrect, ischemic heart disease is the leading cause of death, followed by ischemic stroke and cancer.

The meaning of some sentences is unclear.

What does the author mean in lines 31-32? How does the use of c molecular markers determine the fate of a cell?

Line 46  - "Regulation of neuronal activity occurs by tripartite synapses (receptors, transporters, ion channels) and glio-transmission. Maturation of neural development necessitates synapse formation and synapse pruning referred to consolidation of neural wiring". What does the author mean? What is a tripartite synapse from the author's point of view? What three components does it include?

Lines 50-52 are also completely unclear.

Line 93 - why the author provides information on traumatic brain injury. How does it relate to the topic?

Lines 114-133 list mutant genes of glial cells. With what diseases are they associated? What physiological changes do they lead to? 

Table 1 does not indicate what changes occur with the specified markers - their expression decreases or increases. It does not describe whether these changes are the same or not in different diseases. And are these changes always the same in all the specified areas of the brain?

 

The section "Glial Cells and SB" is critical for the whole manuscript, but it takes up less than one page and contains only two paragraphs of illogical and incomprehensible text. What is astrocytes-related suicide?

The English language should be reviewed by a professional/native speaker. The text is difficult to understand and contains many errors. The author often uses punctuation marks incorrectly.

Author Response

Please See the Attachment

Author Response File: Author Response.docx