Mapping Global Research Trends on Autism Spectrum Disorder: A Bibliometric Analysis of Pharmacology and Pharmacy Studies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The paper titled"Autism Spectrum Disorders:: insight in pharmacology and pharmacy" authors tried to emphasize on the research status of ASD throughout the world. The manuscript is well written but I have some suggestions to authors and hope that it will help them to improve its quality.

1) I am wondering whether it could be considered as review article than research article.  The reason is behind it that these kind of publication trends, author contributions, intitute's and country's contribution used to discussed in the review articles.

2) Author may think about the title of the manuscript. From this manuscript, we are getting the status of the ASD research in the world,  not any pharmacological insights of the ASD.

3) Author may also work on the conclusion. Actually the alignment between results and conclusion is weak and rather requires more attention to make it more relevant. 

Author Response

The paper titled "Autism Spectrum Disorders: insight in pharmacology and pharmacy" authors tried to emphasize on the research status of ASD throughout the world. The manuscript is well written but I have some suggestions to authors and hope that it will help them to improve its quality.

Response: We thank the reviewer for the positive evaluation of our manuscript and for the constructive comments, which have helped us to improve the clarity, positioning, and coherence of the study. All suggestions have been carefully considered and addressed as detailed below.

 

1) I am wondering whether it could be considered as review article than research article. The reason is behind it that these kind of publication trends, author contributions, intitute's and country's contribution used to discussed in the review articles.

Response: We thank the reviewer for this thoughtful comment. We acknowledge that publication trends, author contributions, and institutional or national productivity are frequently discussed within review-type articles. However, we respectfully clarify that the present manuscript is conceived and reported as an original bibliometric research study, rather than a narrative or systematic review.

Unlike systematic reviews, which are designed to synthesize experimental or clinical evidence following frameworks such as PRISMA, the objective of this work is not evidence aggregation or outcome comparison. Instead, we analyze a structured dataset retrieved from the Web of Science and apply quantitative bibliometric methodologies, including science-mapping techniques (VOSviewer and CiteSpace) and classical bibliometric laws (Price, Lotka, Bradford, and Zipf), to generate original analytical outputs.

These methods allow the identification of publication dynamics, collaboration structures, thematic evolution, and translational research fronts, and are widely recognized as constituting primary bibliometric research rather than review-based evidence synthesis. To avoid any ambiguity, we have explicitly clarified the methodological positioning of the study in the Methods section (lines 799-811) and added a dedicated paragraph at the end of the Introduction (lines 93-100) defining the study aim and bibliometric framework.

 

2) Author may think about the title of the manuscript. From this manuscript, we are getting the status of the ASD research in the world,  not any pharmacological insights of the ASD.

Response: We appreciate the reviewer’s comment regarding the manuscript title. We agree that the title should clearly reflect the scope and methodological nature of the study. Accordingly, we have revised the title to better emphasize the bibliometric and analytical perspective of ASD research within the pharmacology and pharmacy domains, rather than direct mechanistic or therapeutic insights.

The revised title now highlights the mapping of research trends, thematic axes, and translational directions relevant to pharmacological research in ASD. The new title is: “Mapping Global Research Trends in Autism Spectrum Disorder: A Bibliometric Analysis of Pharmacology and Pharmacy Studies”.

 

3) Author may also work on the conclusion. Actually the alignment between results and conclusion is weak and rather requires more attention to make it more relevant.

Response: We thank the reviewer for this valuable observation. In response, we have substantially revised and restructured the Conclusions section to strengthen its alignment with the bibliometric results and to enhance its interpretative depth.

Specifically, the revised Conclusions now go beyond a descriptive summary and explicitly synthesize: (i) the temporal growth patterns identified in the analysis; (ii) the role of leading countries and high-impact institutions within the Pharmacology and Pharmacy domain; (iii) the four major thematic axes derived from keyword co-occurrence mapping; and (iv) the translational implications of these trends for pharmacological research and therapeutic development in ASD.

In addition, the revised section emphasizes the evolution of the field toward integrated biological and precision-oriented frameworks, clarifying how the bibliometric evidence informs future research directions and funding priorities. These changes improve coherence between the Results and Conclusions sections and reinforce the scientific contribution and scope of the study. The information modified is included between lines 815-854.

Reviewer 2 Report

Comments and Suggestions for Authors

The work provides bibliometric study analyzing pharmacological research in ASD. The structure is appropriate, and the findings are relevant. To enhance scientific rigor, clarity, and interpretive depth, the following improvements are recommended.

1. Clarify inclusion/exclusion criteria in details to improve reproducibility.
2. Indicate how duplicates, non-pharmacological articles, or borderline articles were handled.
3. Briefly describe how bibliometric laws (Price, Bradford, Zipf, Lotka) were applied and what parameters or thresholds were used.
4. Explain why certain countries/institutions lead productivity—funding, ASD prevalence, infrastructure, or policy drivers.
5. Expand on thematic shifts toward immuno-synaptic interactions, microbiota, and biomarkers—link these trends with modern precision-neuroscience paradigms.
6. Highlight influential authors, journals, or landmark publications that drove field evolution to contextualize citation trends.
7. Add quantitative trends: annual growth rate, h-index values, total citations, and distribution patterns from Bradford zones.
8. Distinguish early-phase topics (2001–2010) versus emerging topics (2018–2025) for a clearer temporal thematic evolution.
9. Expand the conclusion with actionable future directions—e.g., AI-driven drug discovery, neuroimmune interventions, multi-omics biomarker integration—and emphasize gaps in pharmacological ASD research.
10. The following studies are suggested to evaluate and add to the literature review of the manuscript:, https://doi.org/10.14440/jbm.0219, https://doi.org/10.1016/j.jtbi.2025.112059

 

Author Response

The work provides bibliometric study analyzing pharmacological research in ASD. The structure is appropriate, and the findings are relevant. To enhance scientific rigor, clarity, and interpretive depth, the following improvements are recommended.

1. Clarify inclusion/exclusion criteria in details to improve reproducibility.

Response: We thank the reviewer for this valuable suggestion. To improve transparency and reproducibility, a new subsection entitled “Eligibility criteria” has been added to the Materials and Methods section (Lines 799-811). This subsection explicitly details the inclusion and exclusion criteria applied during data selection.

 

 2. Indicate how duplicates, non-pharmacological articles, or borderline articles were handled.

Response: We thank the reviewer for this important comment. The handling of duplicate records, non-pharmacological publications, and borderline articles is now explicitly described in the newly added subsection “Eligibility criteria” (Lines 799-811).

Because the dataset was retrieved exclusively from the Web of Science database and subsequently refined using the predefined filters described in the Materials and Methods section, the downloaded records did not contain duplicate entries. Therefore, no additional deduplication step was required during data curation. Articles classified as borderline were retained only when a clear pharmacological dimension—such as drug exposure, molecular targets, pharmacotherapy, or experimental intervention—was identifiable in the title, abstract, or keywords.

 

3. Briefly describe how bibliometric laws (Price, Bradford, Zipf, Lotka) were applied and what parameters or thresholds were used.

Response: We thank the reviewer for this constructive comment. Classical bibliometric laws were applied following established conventions in bibliometric research. Price’s law was used to assess the exponential growth pattern of annual publication output. Bradford’s law was applied to identify core journals and define Bradford zones based on cumulative publication distributions. Lotka’s law was used to evaluate author productivity patterns, identifying highly productive authors according to inverse-square distributions. Zipf’s law was employed to analyze keyword frequency and thematic prominence. In each case, thresholds were defined using standard bibliometric criteria, retaining the most frequent contributors accounting for approximately one-third of the total output. These methodological details have been added to the main manuscript (Lines 783-798).

 

4. Explain why certain countries/institutions lead productivity—funding, ASD prevalence, infrastructure, or policy drivers.

Response: We thank the reviewer for this insightful comment. The predominance of the United States, China, and selected European countries reflects not only sustained public funding but also the alignment of national science policies, dedicated research infrastructures, and long-term translational programs targeting neurodevelopmental disorders. The presence of specialized centers, coordinated funding schemes, and stable institutional networks appears to be a key enabling factor for leadership in pharmacological ASD research, beyond differences in prevalence or population size.

This interpretation has been incorporated into the main manuscript (Section 2.2; Lines 230-236). In addition, we expanded the analytical perspective in Section 2.2 (Lines 178-183) to explicitly link national funding patterns—particularly in the United States and China—with science and health policy frameworks, biomedical research infrastructure, and translational continuity across basic, preclinical, and pharmacological research stages.

 

5. Expand on thematic shifts toward immuno-synaptic interactions, microbiota, and biomarkers—link these trends with modern precision-neuroscience paradigms.

Response: We thank the reviewer for this valuable suggestion. The observed thematic shifts toward immuno-synaptic interactions, microbiota–gut–brain axis involvement, and biomarker discovery align with contemporary precision-neuroscience paradigms, which emphasize biologically stratified cohorts, biomarker-guided interventions, and multi-system integration in neurodevelopmental disorders. These trends reflect a transition from symptom-based pharmacological approaches toward mechanism-driven strategies that integrate immune, synaptic, and metabolic dimensions of ASD. This expanded interpretation has been incorporated into the manuscript (Lines 557-560), and is further supported by the keyword cluster analysis (Section 2.6, green cluster) and the discussion on emerging biological targets and lead pharmacological strategies (Section 2.6.4).

 

6. Highlight influential authors, journals, or landmark publications that drove field evolution to contextualize citation trends.

Response: We thank the reviewer for this valuable comment. Citation analysis indicates that landmark publications addressing oxytocin signaling, valproic acid–based experimental models, immune dysregulation, and oxidative stress have played a pivotal role in shaping the evolution of pharmacological ASD research. These highly cited studies contributed to consolidating core mechanistic frameworks that subsequently guided thematic diversification. In parallel, influential journals within pharmacology and neuroscience—such as Journal of Child and Adolescent Psychopharmacology, Progress in Neuro-Psychopharmacology & Biological Psychiatry, Neuropsychopharmacology, Neuropharmacology, and Annales Médico-Psychologiques—acted as central dissemination hubs, as reflected by their citation impact (Table 2). These patterns contextualize the observed citation trends and underscore how specific research foci and publication venues have driven field development. This information has been incorporated into the manuscript (Lines 514-518).

 

7. Add quantitative trends: annual growth rate, h-index values, total citations, and distribution patterns from Bradford zones.

Response: We thank the reviewer for this suggestion. Quantitative analysis revealed that the dataset exhibits an h-index of 81, indicating a high cumulative citation impact. Publication output followed an exponential growth pattern, with the most pronounced increase observed after 2015. Application of Bradford’s law identified a small core of high-impact journals accounting for a disproportionate share of total citations, followed by two broader peripheral zones with progressively lower citation densities. These quantitative indicators have been added to the manuscript (Lines 461-464)

 

8. Distinguish early-phase topics (2001–2010) versus emerging topics (2018–2025) for a clearer temporal thematic evolution.

Response: We thank the reviewer for this insightful comment. Bibliometric analysis revealed a clear temporal thematic evolution. Early-phase research (2001-2010) was dominated by behavioral pharmacology, environmental exposure models, and monoaminergic hypotheses. In contrast, recent studies (2018-2025) emphasize immuno-synaptic mechanisms, microbiota–gut–brain interactions, and biomarker-guided therapeutic strategies, reflecting a maturation toward integrative and systems-level pharmacological approaches. This information was incorporated into the manuscript (Lines 450-455).

 

9. Expand the conclusion with actionable future directions—e.g., AI-driven drug discovery, neuroimmune interventions, multi-omics biomarker integration—and emphasize gaps in pharmacological ASD research.

Response: We thank the reviewer for this constructive suggestion. The Conclusions section has been expanded to outline actionable future directions for pharmacological ASD research, including artificial intelligence–assisted drug discovery, neuroimmune-targeted therapeutic strategies, and the integration of multi-omics biomarker platforms. In addition, we explicitly highlight the persistent gap between the growing volume of publications and their limited translational impact, underscoring the need for mechanism-driven, precision-oriented pharmacological approaches. These additions have been incorporated into the Conclusions section (Lines 749-752).

 

10. The following studies are suggested to evaluate and add to the literature review of the manuscript:, https://doi.org/10.14440/jbm.0219, https://doi.org/10.1016/j.jtbi.2025.112059

Response: We thank the reviewer for the suggested references. The first study was carefully evaluated and has been incorporated into the manuscript (Line 611), as it is directly relevant to the pharmacological and bibliometric scope of the present analysis. The second reference was reviewed but not included, as its primary focus does not directly address Autism Spectrum Disorder or pharmacological research in ASD, which constitutes the defined scope of this study.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors summarized the global evolution of research related to autism spectrum disorder over the last 25 years. The manuscript is generally well-written and well-organized.

1. It’s nice to organize by institutions, journals and scientists as well as discuss the interconnections and the general trends. As mentioned in the introduction, there is limited knowledge for ASD mechanism, nor any approved pharmacological treatments for its core symptoms. Authors should add a section to fucus the discussion of the potential biological targets or any lead treatments.

2. Page 2 Line 69. Full name of DSM-5 and ICD-11 should be added here instead of in the results and discussion.

Author Response

The authors summarized the global evolution of research related to autism spectrum disorder over the last 25 years. The manuscript is generally well-written and well-organized.

Response: We thank for your comment and point of view.

 

1. It’s nice to organize by institutions, journals and scientists as well as discuss the interconnections and the general trends. As mentioned in the introduction, there is limited knowledge for ASD mechanism, nor any approved pharmacological treatments for its core symptoms. Authors should add a section to fucus the discussion of the potential biological targets or any lead treatments.

Response: We thank the reviewer for this valuable suggestion. We agree that a clearer emphasis on potential biological targets and lead therapeutic strategies strengthens the translational relevance of the manuscript.

Accordingly, we have expanded the Discussion section by integrating a focused, evidence-based discussion on emerging biological targets and pharmacological leads in ASD, grounded in the bibliometric patterns identified in our analysis. Rather than introducing a standalone review section, this discussion is embedded within the existing thematic interpretation of the results and remains strictly anchored to keyword co-occurrence, model prevalence, and citation trends. Specifically, this new subsection integrates:

(i) recurrent neurobiological targets highlighted by keyword co-occurrence (e.g., excitation/inhibition balance, GABAergic and glutamatergic signaling, immune–microglial pathways, oxidative stress and redox regulation);

(ii) widely used and mechanistically informative preclinical models (e.g., valproic acid–based models); and

(iii) lead pharmacological strategies under active investigation, including oxytocin/vasopressin signaling, redox-modulating agents, microbiota-oriented interventions, and immune-modulatory approaches.

This addition reinforces the connection between bibliometric trends and biologically meaningful targets, thereby improving the clinical and pharmacological interpretability of the results without altering the scope of the study. The new information was added between lines 721-752

 

2. Page 2 Line 69. Full name of DSM-5 and ICD-11 should be added here instead of in the results and discussion.

Response: We thank the reviewer for noting this point. The full names of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) and ICD-11 (International Classification of Diseases, Eleventh Revision) have now been added at their first mention in the Introduction (Lines 70-72), in accordance with standard academic conventions. The subsequent sections now retain only the abbreviated forms.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors performed a bibliometric analysis of global research on autism spectrum disorder (ASD) from 2001 to 2025. They examined publication trends, leading countries, institutions, authors, and key research themes, identifying steady growth in scientific output and major contributors worldwide. the authors analyzed keyword trends to characterize dominant research themes, emphasizing experimental ASD models based on valproic acid and their association with oxidative stress, neurodevelopmental alterations, and synaptic dysfunction.

Overall, the study provides a comprehensive overview of research dynamics, major contributors, and prevailing scientific directions in ASD research.

Major concerns:

Understanding the interplay between immune, synaptic, and behavioral alterations in ASD is crucial for developing targeted therapies and improving treatment outcomes in children. Are there shared biomarkers across the immune, synaptic, and behavioral axes that could predict treatment response to pharmacological interventions in pediatric ASD populations?

Does long-term antipsychotic treatment in children with ASD alter neuroimmune or oxidative stress profiles, potentially impacting neurodevelopmental trajectories?

Can integrative multi-omics approaches (proteomics, metabolomics, transcriptomics) clarify the mechanistic bridges between preclinical animal models and clinical therapeutic outcomes in ASD?

Which combined biomarkers (redox, inflammation, BDNF) most accurately predict individual responses to pharmacological or immunomodulatory therapies in children with ASD? Given that some key markers of oxidative stress and inflammation studied in ASD can also be present in depression, how do the authors plan to distinguish biological signatures specific to ASD from those associated with other neuropsychiatric disorders?

Given the growing emphasis on biology-driven and translational research in ASD, there is increasing interest in identifying biomarkers that can predict individual trajectories and treatment responses. Is there a way to identify early predictive biomarkers that could guide personalized treatment before the onset of symptoms?

Author Response

1. The authors performed a bibliometric analysis of global research on autism spectrum disorder (ASD) from 2001 to 2025. They examined publication trends, leading countries, institutions, authors, and key research themes, identifying steady growth in scientific output and major contributors worldwide. the authors analyzed keyword trends to characterize dominant research themes, emphasizing experimental ASD models based on valproic acid and their association with oxidative stress, neurodevelopmental alterations, and synaptic dysfunction.

Overall, the study provides a comprehensive overview of research dynamics, major contributors, and prevailing scientific directions in ASD research.

Response: Thank you for the precise evaluation and positive consideration of our manuscript for publication. A “point-by-point” response to the reviewers’ comments is outlined below.

 

2. Understanding the interplay between immune, synaptic, and behavioral alterations in ASD is crucial for developing targeted therapies and improving treatment outcomes in children. Are there shared biomarkers across the immune, synaptic, and behavioral axes that could predict treatment response to pharmacological interventions in pediatric ASD populations?

Response: We sincerely thank Reviewer 4 for their thoughtful and insightful comments, which substantially strengthen the translational perspective of our work. In the revised Discussion, we integrate evidence highlighting convergent immune, oxidative, and neurotrophic alterations implicated in ASD pathophysiology. Rather than proposing validated predictors of treatment response, we frame these biomarkers as biologically relevant candidates for patient stratification and for future investigation of pharmacological responsiveness in pediatric ASD populations. This information was included between lines 651-664.

 

3. Does long-term antipsychotic treatment in children with ASD alter neuroimmune or oxidative stress profiles, potentially impacting neurodevelopmental trajectories?

Response: We agree that this is a highly relevant question. Although children with ASD exhibit baseline immune and oxidative stress alterations, robust longitudinal evidence directly linking long-term antipsychotic treatment to sustained changes in neuroimmune or oxidative stress profiles in pediatric ASD remains limited to date. Nevertheless, experimental and clinical literature suggests that atypical antipsychotics may influence mitochondrial and metabolic pathways, supporting biological plausibility for interactions with redox and immune systems during neurodevelopment. This gap highlights the need for longitudinal biomarker-based studies in treated ASD cohorts. This information was included between lines 665-675.

 

4. Can integrative multi-omics approaches (proteomics, metabolomics, transcriptomics) clarify the mechanistic bridges between preclinical animal models and clinical therapeutic outcomes in ASD?

Response: We thank Reviewer 4 for this important question. We agree that integrative multi-omics approaches represent a promising strategy to elucidate mechanistic links between preclinical models and human ASD biology. Accordingly, we expanded the Discussion to highlight recent systems-level and multi-omics studies, as well as conceptual reviews, illustrating how integrative frameworks can support translational inference. We also explicitly acknowledge that fully unified and longitudinal multi-omics datasets directly linking animal models to clinical therapeutic outcomes in ASD remain limited. This information was included between lines 676-686.

Taken together, these findings suggest that integrative multi-omics approaches can conceptually bridge preclinical and clinical domains in ASD, although their current contribution remains primarily hypothesis-generating rather than outcome-predictive.

 

5. Which combined biomarkers (redox, inflammation, BDNF) most accurately predict individual responses to pharmacological or immunomodulatory therapies in children with ASD? Given that some key markers of oxidative stress and inflammation studied in ASD can also be present in depression, how do the authors plan to distinguish biological signatures specific to ASD from those associated with other neuropsychiatric disorders?

Response: We appreciate this thoughtful comment. In the revised manuscript, we emphasize that single inflammatory or oxidative biomarkers lack diagnostic specificity due to substantial overlap across neuropsychiatric conditions, including depression. We therefore highlight the potential value of composite biomarker panels integrating inflammatory (e.g., IL-6, TNF-α), redox (e.g., GSH/GSSG), and neurotrophic (e.g., BDNF) measures as a strategy for biological stratification rather than categorical diagnosis. Current evidence indicates that while ASD shares inflammatory and oxidative features with mood disorders, differences in the pattern, magnitude, and developmental context of these alterations may contribute to probabilistic stratification of ASD-related biological profiles. Importantly, we acknowledge that the predictive value of such biomarker constellations for individual therapeutic response in ASD remains to be validated in longitudinal and treatment-focused studies. This information was included between lines 687-704.

 

6. Given the growing emphasis on biology-driven and translational research in ASD, there is increasing interest in identifying biomarkers that can predict individual trajectories and treatment responses. Is there a way to identify early predictive biomarkers that could guide personalized treatment before the onset of symptoms?

Response: We sincerely thank the reviewer for highlighting this important and timely aspect of translational autism research. We fully agree that identifying early biological markers capable of predicting individual developmental trajectories and treatment responsiveness is a significant goal in the field. In response to this comment, we have revised the Discussion to clarify the current state of evidence, emphasising that while no early-life biomarkers have yet been clinically validated to guide personalised treatment before symptom onset, accumulating data point to specific biological pathways, particularly oxidative stress and neurotrophic signaling, as promising candidates for future longitudinal investigation. We have therefore framed these markers as mechanistically relevant and biologically plausible contributors to early risk stratification, rather than established predictive tools. This information was included between lines 705-717

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I don't have any further comments. Best of luck.  

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have satisfactorily addressed all the comments and incorporated the suggested revisions. The manuscript has improved in clarity, completeness, and readability. I find the revised version appropriate for publication in its current form.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have satisfactorily addressed my comments. Hence I recommend publication in Pharmaceuticals.