Reviewer’s report
Title: 
Pain and psyche in a patient with irritable bowel syndrome—chicken or
egg? A time series case report
Version: 
0 
Date: 
04 Jan 2021
Reviewer's report:
The paper by Engel and colleagues provides an interesting and potentially useful
insight into the relationship between psychological traits and gastrointestinal
symptoms in an individual diagnosed with Rome irritable bowel syndrome
(IBS). The authors take a time-series approach to understanding the bi-
directional relationships between psychological factors and symptom experience,
concluding that symptoms precede psychological events more so than the other
way around. Their findings stand in some contrast to the usual bi-directional
view of brain-gut interactions.
The authors conclusions are generally well supported, however there are a few
points that I believe need clarification.
1. An intensive study of a single individual yields insights at a very detailed level
that are difficult to achieve when studying groups, and the authors allude to this
when discussing previous work that revolved around averages. I agree with the
benefits of the approach they have taken. However there is also a price to pay in
that generalising from one patient to the population of patients does not
automatically follow, and this could potentially explain some of the
discrepancies they report between this work and previous studies. I expect the
authors understand this but I think it needs to be drawn out more explicitly in
both the Introduction and Discussion.
2. Are somatic symptoms in Table 4 an average of abdominal pain and daily
impairment in Table 3? I was not clear on exactly how SS is measured.
3. Another point that I was not clear on is whether all combinations of
psychological variables predicting symptom level and vice versa were
calculated, and only the statistically significant findings reported in Table 4. I
think this is what happened but clarification in the text would be useful.
4. The column heading "h=10" in Table 4 is not explained.
5. Statistical terminology needs to be more carefully defined, for example the
term "instantaneous correlation" presumably means correlation between SS and
psych at a given time, but the reader should not have to guess. Similarly, line
165 on page 6 lists a number of statistical analyses conducted but not what they
represent or how they contribute to answering the study's research questions. I
think a more careful explanation and possibly being more selective about which
statistical analyses are reported would help this paper. The authors' conclusions
hang on this unusual, for the field, statistical approach and hence a clear and
specific explanation is important.
6. This is a specific example of my previous point but is absolutely central to the
paper. On page 6, starting line 171, the concept of Granger-causality is explained
but only in one sentence. This seems to me to be the single most important
concept in this work and needs to be teased out further such that the clinical
interpretation is clear to a non-statistical reader. Without understanding what
Granger-causality means in a tangible sense I do not see how the reader can
judge whether they agree with the interpretation provided.
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No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Pain and psyche in a patient with irritable bowel syndrome—chicken or
egg? A time series case report
Version: 
0 
Date: 
04 Jan 2021
Reviewer's report:
The paper by Engel and colleagues provides an interesting and potentially useful
insight into the relationship between psychological traits and gastrointestinal
symptoms in an individual diagnosed with Rome irritable bowel syndrome
(IBS). The authors take a time-series approach to understanding the bi-
directional relationships between psychological factors and symptom experience,
concluding that symptoms precede psychological events more so than the other
way around. Their findings stand in some contrast to the usual bi-directional
view of brain-gut interactions.
The authors conclusions are generally well supported, however there are a few
points that I believe need clarification.
1. An intensive study of a single individual yields insights at a very detailed level
that are difficult to achieve when studying groups, and the authors allude to this
when discussing previous work that revolved around averages. I agree with the
benefits of the approach they have taken. However there is also a price to pay in
that generalising from one patient to the population of patients does not
automatically follow, and this could potentially explain some of the
discrepancies they report between this work and previous studies. I expect the
authors understand this but I think it needs to be drawn out more explicitly in
both the Introduction and Discussion.
2. Are somatic symptoms in Table 4 an average of abdominal pain and daily
impairment in Table 3? I was not clear on exactly how SS is measured.
3. Another point that I was not clear on is whether all combinations of
psychological variables predicting symptom level and vice versa were
calculated, and only the statistically significant findings reported in Table 4. I
think this is what happened but clarification in the text would be useful.
4. The column heading "h=10" in Table 4 is not explained.
5. Statistical terminology needs to be more carefully defined, for example the
term "instantaneous correlation" presumably means correlation between SS and
psych at a given time, but the reader should not have to guess. Similarly, line
165 on page 6 lists a number of statistical analyses conducted but not what they
represent or how they contribute to answering the study's research questions. I
think a more careful explanation and possibly being more selective about which
statistical analyses are reported would help this paper. The authors' conclusions
hang on this unusual, for the field, statistical approach and hence a clear and
specific explanation is important.
6. This is a specific example of my previous point but is absolutely central to the
paper. On page 6, starting line 171, the concept of Granger-causality is explained
but only in one sentence. This seems to me to be the single most important
concept in this work and needs to be teased out further such that the clinical
interpretation is clear to a non-statistical reader. Without understanding what
Granger-causality means in a tangible sense I do not see how the reader can
judge whether they agree with the interpretation provided.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Pain and psyche in a patient with irritable bowel syndrome—chicken or
egg? A time series case report
Version: 
0 
Date: 
04 Jan 2021
Reviewer's report:
The paper by Engel and colleagues provides an interesting and potentially useful
insight into the relationship between psychological traits and gastrointestinal
symptoms in an individual diagnosed with Rome irritable bowel syndrome
(IBS). The authors take a time-series approach to understanding the bi-
directional relationships between psychological factors and symptom experience,
concluding that symptoms precede psychological events more so than the other
way around. Their findings stand in some contrast to the usual bi-directional
view of brain-gut interactions.
The authors conclusions are generally well supported, however there are a few
points that I believe need clarification.
1. An intensive study of a single individual yields insights at a very detailed level
that are difficult to achieve when studying groups, and the authors allude to this
when discussing previous work that revolved around averages. I agree with the
benefits of the approach they have taken. However there is also a price to pay in
that generalising from one patient to the population of patients does not
automatically follow, and this could potentially explain some of the
discrepancies they report between this work and previous studies. I expect the
authors understand this but I think it needs to be drawn out more explicitly in
both the Introduction and Discussion.
2. Are somatic symptoms in Table 4 an average of abdominal pain and daily
impairment in Table 3? I was not clear on exactly how SS is measured.
3. Another point that I was not clear on is whether all combinations of
psychological variables predicting symptom level and vice versa were
calculated, and only the statistically significant findings reported in Table 4. I
think this is what happened but clarification in the text would be useful.
4. The column heading "h=10" in Table 4 is not explained.
5. Statistical terminology needs to be more carefully defined, for example the
term "instantaneous correlation" presumably means correlation between SS and
psych at a given time, but the reader should not have to guess. Similarly, line
165 on page 6 lists a number of statistical analyses conducted but not what they
represent or how they contribute to answering the study's research questions. I
think a more careful explanation and possibly being more selective about which
statistical analyses are reported would help this paper. The authors' conclusions
hang on this unusual, for the field, statistical approach and hence a clear and
specific explanation is important.
6. This is a specific example of my previous point but is absolutely central to the
paper. On page 6, starting line 171, the concept of Granger-causality is explained
but only in one sentence. This seems to me to be the single most important
concept in this work and needs to be teased out further such that the clinical
interpretation is clear to a non-statistical reader. Without understanding what
Granger-causality means in a tangible sense I do not see how the reader can
judge whether they agree with the interpretation provided.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant