Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

The manuscript represents a thoughtful and well-structured review of a highly relevant topic in translational neuropsychiatry. The authors have clearly put substantial effort in identifying and organizing behavioral assays with cross-species analogs, making the work both informative and engaging for a broad readership. Importantly, the manuscript provides valuable insight into newer and sophisticated tasks that better capture specific domains of depression and help bridge the translational gap between animal and human research.

Key strengths include the high relevance of the topic, quality of presentation, interest to readers, and a comprehensive description of ten major tasks. However, several limitations reduce the overall impact. Most notably, the search strategy appears relatively narrow, and using only PubMed as a single database limits its relevance. In addition, the Analysis is largely descriptive, lacking systematic comparison or evaluation of task validity.

To strengthen the manuscript, it would be beneficial to include a summary table highlighting the strengths and limitations of each task, along with an assessment of their validity (face, construct, predictive). Furthermore, a more explicit comparison—and potentially a ranking—of tasks based on their translational value would enhance the scientific value/contribution of this review.

Required Improvements:

- Broaden search strategy and consider including additional databases.

 - Include a summary table for each task with advantages, limitations, and validity ratings.

- Provide a comparison or ranking of tasks by their translational relevance.

- Highlight any gaps in validation (e.g., stress models, patient populations).

Overall: The manuscript is promising and of high interest, but requires methodological and organizational enhancements to strengthen its scientific rigor and impact.

Author Response

Comment 1: Broaden search strategy and consider including additional databases.

Response 1: We have now included the the Web of Science database to our search.

Comment 2: Include a summary table for each task with advantages limitations, and validity ratings.

Response 2: We have now modified the tables to include these descriptions.

Comment 3: Provide a comparison or ranking of tasks by their translational relevance.

Response 3: We have modified our tables to include the advantages and limitations of each task. We leave the reader to determine which tasks are best for their use case.

Comment 4: Highlight any gaps in validation (e.g., stress models, patient populations).

Response 4: We have now elaborated on validation gaps in human and rodent studies in the discussion (523-529).

Reviewer 2 Report

Comments and Suggestions for Authors

This review article summarizes behavioral rodent tests used in depression research. The topic is of high relevance, given the challenge of modeling a complex and uniquely human condition such as depression in rodents. The manuscript is generally well structured and clearly written. I only have a few minor comments aimed to improve the clarity and presentation.

1. I suggest reorganizing Table 1 by separating human and rodent studies. Additionally, creating separate rows for each main finding, with explicit reference attribution, would improve clarity and facilitate a better understanding of the current literature.
2. I suggest schematic representations of all described behavioral tasks. That would improve consistency and make the review more comprehensible to the reader.
3. Please verify the description of reference 63. In this study, the authors did not examine antidepressant effects, only different pro-depressant manipulations.

Author Response

Comment 1: I suggest reorganizing Table 1 by separating human and rodent studies. Additionally, creating separate rows for each main finding, with explicit reference attribution, would improve clarity and facilitate a better understanding of the current literature.

Response 1: We have now split the table into two separate tables. We also revised the formatting of the references to match those in the manuscript, and elaborated on key advantages and disadvantages.

Comment 2: I suggest schematic representations of all described behavioral tasks. That would improve consistency and make the review more comprehensible to the reader.

Response 2: We have now provided an additional  figure providing schematic representations of the remaining tasks.

Comment 3: Please verify the description of reference 63. In this study, the authors did not examine antidepressant effects, only different pro-depressant manipulations.

Response 3: Thank you for pointing this out. We have corrected this to the description of reference 64 (line 504).

Reviewer 3 Report

Comments and Suggestions for Authors

This interesting review article employs a systematic review methodology to identify behavioral tasks which are direct cross-species analogs between rodents and humans. It is valuable for translational depression research. The authors identified 10  behavioral tests with comparable human and rodent versions, characterized them, and discussed their respective strengths and limitations. The cited references are appropriately recent, such as this work provides  up-to-date valuable synthesis. But to enhance transparency and adhere to PRISMA reporting guidelines (https://www.prisma-statement.org/), I would suggest providing a brief summary of the basic characteristics for each of the 44 studies used for this systematic review. This would be useful for readers and would help to structure the review properly. Additionally, I have a few suggestions that could help strengthen the manuscript even further.

Specific comments:

Lines 45-52 This section could be improved by providing a short outline of MDD multifactorial etiology. It would be helpful to focus on how genetic and non-genetic factors each contribute to risk.

Lines 104-112 I would suggest that the authors specify which particular symptom domains of depression they selected at this step. It would also strengthen the methodology to state how these domains were translated into the specific search terms. To enhance study replication and transparency, I would also suggest specifying the logical operators (e.g. AND/OR) used within and between the search terms.

Lines 155-156 I recommend including typical  example to illustrate the exclusion criterion regarding absence of a ”directly translatable” behavioral test.

Lines 156-157 To enhance transparency and adhere to PRISMA reporting guidelines, I recommend providing a summary of basic characteristics for each of the 44 included studies. The authors could arrange these characteristics in a table or in a supplementary spreadsheet. Specifically, for animal studies, this should include not only behavioral task, but also rodent species/strain, sex, sample size, and the disease model used if applicable. For human studies, the appropriate population details should also be provided.

Figure 1 In the bottom right picture, ”Hedonic perception threshold“ is not accurate. It mixes concepts of threshold (detection) and hedonic (liking). Please reconsider this wording.

Line 234 Please decipher abbreviation rCPT at first use.

Lines 449-452 Citation for Harfmann et al.  missing.

Lines 591-592 Please consider revising this sentence to address a potential inconsistency. It is noted that the rodent version is not directly analogous, otherwise it is not clear how the reviewed studies had passed the filters for directly translatable paradigms.

Lines 615-616 Please consider expanding the discussion of limitations associated with rodent-human cross-species behavioral tasks. More detailed examination of differences in higher cognitive abilities (e.g. abstract reasoning, complexity) and sensory systems specificity (e.g. reliance on olfaction vs. vision, ultrasonic hearing) would help readers appreciate the difficulties of direct translation.

Line 638 Typo “can mapped” maybe should be “can be mapped”?

Table S1 (1) Please unify abbreviations in the table. Most are deciphered (e.g. JBT, CBT), but several others (e.g. RT, mABT) are not. Please ensure all abbreviations are with definitions. Maybe it would be even more helpful to put all the abbreviations in a footnote. (2) Please, clarify the ”references” column. If these correspond to the same sources from the main text, it would be better to link them to the corresponding main bibliography reference numbers. (3) Reference Harfmann et al. lacks year. (4) Minor taxonomic correction: in the ”Key findings in rodents“ section, marmosets are listed with rats and mice. As marmosets are primates, please  make corrections.

Author Response

Comment 1: Lines 45-52 This section could be improved by providing a short outline of MDD multifactorial etiology. It would be helpful to focus on how genetic and non-genetic factors each contribute to risk.

Response 1: Thank you for this suggestion. We have now included this in the introduction (54-57).

Comment 2: Lines 104-112 I would suggest that the authors specify which particular symptom domains of depression they selected at this step. It would also strengthen the methodology to state how these domains were translated into the specific search terms. To enhance study replication and transparency, I would also suggest specifying the logical operators (e.g. AND/OR) used within and between the search terms.

Response 2: Thank you for this suggestion. We have clarified the symptom domains we selected and added logical operators in our search strategy (113-117).

Comment 3: Lines 155-156 I recommend including typical  example to illustrate the exclusion criterion regarding absence of a ”directly translatable” behavioral test.

Response 3: We have now elaborated on this in the methods (175-176).

Comment 4: Lines 156-157 To enhance transparency and adhere to PRISMA reporting guidelines, I recommend providing a summary of basic characteristics for each of the 44 included studies. The authors could arrange these characteristics in a table or in a supplementary spreadsheet. Specifically, for animal studies, this should include not only behavioral task, but also rodent species/strain, sex, sample size, and the disease model used if applicable. For human studies, the appropriate population details should also be provided.

Response 4: We believe these details are beyond the scope of the paper, but the references have been provided for readers that would like to read about these details.

Comment 5: Figure 1 In the bottom right picture, “Hedonic perception threshold” is not accurate. It mixes concepts of threshold (detection) and hedonic (liking). Please reconsider this wording.

Response 5: We have now clarified this and changed the term to “Sucrose Hedonic Response”

Comment 6: Line 234 Please decipher abbreviation rCPT at first use.

We have now clarified the rCPT in results (267-268).

Comment 7: Lines 449-452 Citation for Harfmann et al.  missing.

Response 7: We have now included this citation in the references.

Comment 8: Lines 591-592 Please consider revising this sentence to address a potential inconsistency. It is noted that the rodent version is not directly analogous, otherwise it is not clear how the reviewed studies had passed the filters for directly translatable paradigms.

Response 8: We have now corrected this in the discussion (632-633).

Comment 9: Lines 615-616 Please consider expanding the discussion of limitations associated with rodent-human cross-species behavioral tasks. More detailed examination of differences in higher cognitive abilities (e.g. abstract reasoning, complexity) and sensory systems specificity (e.g. reliance on olfaction vs. vision, ultrasonic hearing) would help readers appreciate the difficulties of direct translation.

Response 9: We have now included this in the discussion and future directions (658-660, 705-708).

Comment 10: Line 638 Typo “can mapped” maybe should be “can be mapped”?

Response 10: We have now corrected this error (687).

Comment 11: Table S1 (1) Please unify abbreviations in the table. Most are deciphered (e.g. JBT, CBT), but several others (e.g. RT, mABT) are not. Please ensure all abbreviations are with definitions. Maybe it would be even more helpful to put all the abbreviations in a footnote. (2) Please, clarify the ”references” column. If these correspond to the same sources from the main text, it would be better to link them to the corresponding main bibliography reference numbers. (3) Reference Harfmann et al. lacks year. (4) Minor taxonomic correction: in the ”Key findings in rodents“ section, marmosets are listed with rats and mice. As marmosets are primates, please  make corrections.

Response 11: We have now added a footnote with the abbreviations, clarified the references, and corrected the table to be consistent with rodent findings.

Reviewer 4 Report

Comments and Suggestions for Authors

Summary

This manuscript addresses an important translational question in depression research and is generally well organized. A key strength is its focus on symptom-relevant cross-species processes rather than broad “depression-like” claims. However, the review is methodologically closer to a scoping-style mapping exercise than to a rigorous systematic review, mainly because the search is narrow and no structured quality assessment is provided. Overall, the manuscript is useful, but revision is needed before publication.

 

Major Comments

1. The manuscript is presented as a systematic review, but the methods are closer to a scoping-style review because the paper follows PRISMA-ScR logic and does not include formal quality appraisal. Please clarify the review type in the title, abstract, and methods. Please ensure that the terminology matches the method actually used.
2. The search appears to rely solely on PubMed, which seems too narrow for a topic spanning psychiatry, behavioral neuroscience, and experimental psychology. Please either expand the search across additional databases or provide a stronger justification for the current strategy.
3. The search terms do not seem sufficiently aligned with the manuscript’s actual review question. The review is organized around specific cross-species paradigms, but the reported search strategy is framed mainly around broad symptom terms rather than task-centered keywords. Please explain this mismatch more clearly or revise the search strategy accordingly.
4. The search strategy is not reported in enough detail to be fully reproducible. Although example search phrases are provided, the manuscript does not include the full Boolean logic or database-ready syntax. Please provide the complete search strings in a transparent and auditable format.

 

Minor Comments

1. The task schematic figure is useful for orientation, but it mainly illustrates conceptual correspondence. Please clarify in the legend that the figure does not by itself establish strict cross-species equivalence.
2. The conclusion is slightly more confident than the evidence base currently allows. Please make the final paragraph more graded so that it better reflects the uneven validation across task classes.

Author Response

Comment 1: The manuscript is presented as a systematic review, but the methods are closer to a scoping-style review because the paper follows PRISMA-ScR logic and does not include formal quality appraisal. Please clarify the review type in the title, abstract, and methods. Please ensure that the terminology matches the method actually used.

Response 1: We are now presenting this paper as a review.

Comment 2: The search appears to rely solely on PubMed, which seems too narrow for a topic spanning psychiatry, behavioral neuroscience, and experimental psychology. Please either expand the search across additional databases or provide a stronger justification for the current strategy.

Response 2: We have now included Web of Science in our search

Comment 3: The search terms do not seem sufficiently aligned with the manuscript’s actual review question. The review is organized around specific cross-species paradigms, but the reported search strategy is framed mainly around broad symptom terms rather than task-centered keywords. Please explain this mismatch more clearly or revise the search strategy accordingly.

Response 3: The search strategy focuses on broad symptom terms to comprehensively capture all relevant articles. We excluded many of these studies as they did not contain a directly translatable behavior test.

Comment 4: The search strategy is not reported in enough detail to be fully reproducible. Although example search phrases are provided, the manuscript does not include the full Boolean logic or database-ready syntax. Please provide the complete search strings in a transparent and auditable format.

Response 4: We have now included logical operators in our search strategy (115-117).

Comment 5: The task schematic figure is useful for orientation, but it mainly illustrates conceptual correspondence. Please clarify in the legend that the figure does not by itself establish strict cross-species equivalence.

Response 5: We have now clarified this in the figure caption.

Comment 6: The conclusion is slightly more confident than the evidence base currently allows. Please make the final paragraph more graded so that it better reflects the uneven validation across task classes.

Response 6: We have now elaborated on the uneven validation in our conclusion (728).

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors, 

I commend you for making a clear effort to address the majority of the reviewers’ comments, and the manuscript has improved in several important aspects. In particular, the addition of discussion on validation gaps, as well as the inclusion of strengths and limitations for each task, enhances the overall clarity and usefulness of the review.

One point that may still benefit from consideration is the absence of an explicit comparative synthesis across behavioral tasks. While informative, the manuscript remains largely descriptive, and a brief integrative perspective could further strengthen its impact.

While not essential for acceptance, I believe that incorporating such a comparative element would further improve the manuscript and enhance its overall impact.

Kind regards, 

Author Response

Comment 1: One point that may still benefit from consideration is the absence of an explicit comparative synthesis across behavioral tasks. While informative, the manuscript remains largely descriptive, and a brief integrative perspective could further strengthen its impact.

Response 1: We have now included a comparative synthesis in the discussion (4.12).

Reviewer 3 Report

Comments and Suggestions for Authors

Overall I'm satisfied with the introduced revisions.

A minor comment

Please ensure that Abstract corresponds with the revised Results section. Maybe the numbers of 'studies' and 'included studies' (lines 31-32) should be corrected?

 

Author Response

Comment 1: Please ensure that Abstract corresponds with the revised Results section. Maybe the numbers of 'studies' and 'included studies' (lines 31-32) should be corrected?

Response 1: Thank you for finding this. We have now corrected the Abstract to match the Results section.