PEER REVIEW HISTORY ARTICLE DETAILS TITLE (PROVISIONAL)

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1 PEER REVIEW HISTORY BMJ Open publishes all reviews undertaken for accepted manuscripts. Reviewers are asked to complete a checklist review form ( and are provided with free text boxes to elaborate on their assessment. These free text comments are reproduced below. This paper was submitted to a another journal from BMJ but declined for publication following peer review. The authors addressed the reviewers comments and submitted the revised paper to BMJ Open. The paper was subsequently accepted for publication at BMJ Open. TITLE (PROVISIONAL) AUTHORS REVIEWER REVIEW RETURNED GENERAL COMMENTS ARTICLE DETAILS Multisite musculoskeletal pain in adolescence and later mental health disorders: a population-based registry study of Norwegian youth: The NAAHS cohort study. Eckhoff, Christian; Straume, Bjørn; Kvernmo, Siv VERSION 1 - REVIEW Daniel Whibley Epidemiology Group, University of Aberdeen, Scotland, UK 03-Feb-2016 Adolescent musculoskeletal pain predicts mental health problems in young adulthood. I read your article with interest and conducted my review in accordance with STROBE guidelines. Page numbers refer to the generated PDF (the number in top left corner of the document). Overall your study has very interesting findings. The comments largely refer to the language you use and the emphasis placed on the confounding role of psychosocial factors. I have listed suggestions where I believe improvements could be made to the manuscript. Page 2 Please indicate the study s design in the title or abstract Line 18: Data were obtained from a linkage between the Norwegian Patient Registry ( ) and the Norwegian Arctic Adolescent Health Study, a school-based survey in North Norway ( ) conducted among 3,987 10th grade students (70%). I am unclear what the denominator is in the proportion. Is this 70% of all 10th grade students in Norway? If so, please state. Line 31: Rather than It supports, I would suggest This finding supports However in the next sentence you contradict this statement by stating that the relationship was confounded. At this point I begin to question whether you identified any association that could not be

2 explained by confounding. Line 37: other physical factors is somewhat vague. I would suggest stating the factors, or at least what kind of physical factors you are referring to (I presume it is musculoskeletal pain, sedentary activity and physical activity, as listed in the table on p.10). Line 37: You state that differences in predictors for different mental health disorders occurred. You are using the same predictor (musculoskeletal pain sites), or at least I assume you are at this stage as you have not stated otherwise. If you mean number of musculoskeletal pain sites was differentially predictive depending on the mental health disorder, please make this clear. Line 45: As you state that the relationship is confounded it seems strange to conclude that the relationship exists and clinicians should examine for the confounder. Please support this recommendation with a clear explanation. Page 3. Line 7: You state Multisite pain is more associated with psychosocial and mental health problems than single-site pain. I think you mean multisite pain is more associated with psychosocial and mental health problems than single-site pain is. This is very subtle but important as it changes the meaning of the sentence. Page 4. Line 7: Again: You state Multisite pain is more associated with psychosocial and mental health problems than single-site pain. I think you mean multisite pain is more associated with psychosocial and mental health problems than single-site pain is. This is very subtle but important as it changes the meaning of the sentence. Line 27: physical pain. I would suggest amending to musculoskeletal pain if this is specifically what you mean. Line 39: To determine the importance of physical factors. What do you mean by physical factors? Please make clear. You use physical factors to refer to musculoskeletal pain, sedentary activity and physical activity in the analysis but in the discussion (p13, line 38) you include fatigue. Line 49: You do not state any exclusion criteria. If there were none, please state. Page 5. Line 30 In order to control the proportion This sentence is confusing. Please describe the methods used to control.

3 You do not provide an explanation regarding how study size was arrived at. Please include. Page 7. Line 58. You state that factors across different samples were similar. This is vague. Did you statistically analyse differences. If no significant differences exist, please state this. A supplementary file is suggested. Page 8. Line 16. You do not need hyphens after sociodemographic and physical. Lines This sentence could be re-worded to improve clarity. Line 21. Throughout you use physical when I believe you are referring to musculoskeletal pain, sedentary activity and physical activity. Being more specific would assist in focusing the reader s mind. The following description of the statistical models in this paragraph is hard to follow the model building could be described in a more straight-forward way. P10. Table 1. You do not provide reference categories in the table. Please include, or at least make clear what the odds ratio refers to when it is not apparent, e.g. rather than gender use female. P11. Line 10. You state that musculoskeletal pain lost its significance in the final (fully adjusted model). This makes me question the title of the paper. P12. Line 54. The amount of variance explained is quite low and could be random noise. Please provide justification for the validity of the models. P13 Line 20 This association was confounded by psychosocial problems, not by other physical factors. Does this mean the relationship was not confounded by sedentary or physical activity? If so, please be specific. Line 31. the relationship between adolescent musculoskeletal pain and later mental health problems was confounded by adolescent psychosocial problems. This recurrent message makes me question the association in the title. Have you considered psychosocial factors as different type of variable, at least conceptually, e.g. mediators or moderators of the relationship? A discussion of this literature, and a theoretical explanation of the confounding relationship would strengthen your argument.

4 VERSION 1 AUTHOR RESPONSE We would like to thank reviewer 1 for a thorough reading of our manuscript and the positive feedback. We are thankful for the constructive comments and suggestions, which will improve the quality of our manuscript. Our responses are in bold letters and referrals are to the revised manuscript. The changes to the manuscript are in cursive. Comments to the Author Adolescent musculoskeletal pain predicts mental health problems in young adulthood. I read your article with interest and conducted my review in accordance with STROBE guidelines. Page numbers refer to the generated PDF (the number in top left corner of the document). Overall your study has very interesting findings. The comments largely refer to the language you use and the emphasis placed on the confounding role of psychosocial factors. I have listed suggestions where I believe improvements could be made to the manuscript. Reply: We agree that improvements could be made to the language of the manuscript. We are thankful for the suggestive comments. The term confounding has been changed to mediating, which is possibly a better description of the role of the psychosocial factors. A reply to each comment follows and changes have been made to the revised manuscript. Page 2 Please indicate the study s design in the title or abstract Reply: Title page, lines 1-3. The NAAHS cohort study has been added to the manuscript title. The relationship between multisite musculoskeletal pain in adolescence and mental health disorders in young adulthood The NAAHS cohort study. Line 18: Data were obtained from a linkage between the Norwegian Patient Registry ( ) and the Norwegian Arctic Adolescent Health Study, a school-based survey in North Norway ( ) conducted among 3,987 10th grade students (70%). I am unclear what the denominator is in the proportion. Is this 70% of all 10th grade students in Norway? If so, please state.

5 Reply: Abstract, page 1, lines Following changes made:, a school-based survey responded by 3,987 out of 5,877 (70%) of all 10 th grade students in North Norway ( ). Line 31: Rather than It supports, I would suggest This finding supports However in the next sentence you contradict this statement by stating that the relationship was confounded. At this point I begin to question whether you identified any association that could not be explained by confounding. Reply: The abstract has been changed. The mentioned sentence containing It supports has been removed. The term confounded has been replaced by mediated/mediators. Line 37: other physical factors is somewhat vague. I would suggest stating the factors, or at least what kind of physical factors you are referring to (I presume it is musculoskeletal pain, sedentary activity and physical activity, as listed in the table on p.10). Reply: Abstract, page 1, line 21. Following changes:, not by physical or sedentary activity. Line 37: You state that differences in predictors for different mental health disorders occurred. You are using the same predictor (musculoskeletal pain sites), or at least I assume you are at this stage as you have not stated otherwise. If you mean number of musculoskeletal pain sites was differentially predictive depending on the mental health disorder, please make this clear. Reply: Abstract, page 1, line Following changes: However, when examining the different mental health disorders we found musculoskeletal pain to be significantly associated with anxiety disorders, and showing a strong trend in mood disorders, when adjusted for the adolescent factors. Line 45: As you state that the relationship is confounded it seems strange to conclude that the relationship exists and clinicians should examine for the confounder. Please support this recommendation with a clear explanation.

6 Reply: Abstract, page 1, line Following changes: Physicians should be aware that multisite adolescent pain is associated with mental health problems in adolescence, and that these adolescents are at increased risk of mental health disorders in young adulthood. As youth troubled by mental health problems commonly present physical complaints it is important to examine for psychosocial problems in order to offer early interventions. Page 3. Line 7: You state Multisite pain is more associated with psychosocial and mental health problems than single-site pain. I think you mean multisite pain is more associated with psychosocial and mental health problems than single-site pain is. This is very subtle but important as it changes the meaning of the sentence. Reply: Page 2. This sentence has been replaced by new bullet point according to the journal requirements. Page 4. Line 7: Again: You state Multisite pain is more associated with psychosocial and mental health problems than single-site pain. I think you mean multisite pain is more associated with psychosocial and mental health problems than single-site pain is. This is very subtle but important as it changes the meaning of the sentence. Reply: Intro, page 3, line 4. Following changes:,and multisite pain is more associated with psychosocial and mental health problems than single-site pain is. Line 27: physical pain. I would suggest amending to musculoskeletal pain if this is specifically what you mean. Reply: We do not mean musculoskeletal pain specifically as the referred studies also included other types of pain. Still, the following changes have been made: physical pain has been changed to just pain in the introduction, page 3, line 7, and write musculoskeletal pain when we specifically mean it.

7 Line 39: To determine the importance of physical factors. What do you mean by physical factors? Please make clear. You use physical factors to refer to musculoskeletal pain, sedentary activity and physical activity in the analysis but in the discussion (p13, line 38) you include fatigue. Reply: - Introduction, page 3, line Following changes: Secondly, to determine the importance of musculoskeletal pain in relation to later mental healthcare use and mental health disorders, when adjusting for adolescent psychosocial factors. Line 49: o The term physical factors has been changed to the either musculoskeletal pain, sedentary activity and physical activity were appropriate in the manuscript. - The term fatigue has been removed in the discussion as a general example of physical problems related to mental health problems. Makes it simpler and clearer. You do not state any exclusion criteria. If there were none, please state. Reply: Methods, page 4, lines Following changes: There were no specific exclusion criteria in this study. Page 5. Line 30 In order to control the proportion This sentence is confusing. Please describe the methods used to control. You do not provide an explanation regarding how study size was arrived at. Please include. Reply: Methods, page 4 lines and page 5 lines 1 2. Following changes: In order to explore the representativeness of the proportion of mental healthcare users in our sample (30% nonresponders), the NPR calculated the total number of mental healthcare users in Northern Norway with the same age and registration period as the study sample. The total number of patients (n=850) was compared to the total population data from Statistics Norway public database (n=5,715) to give and approximate cumulative prevalence of mental health care users in the total population, which we compared our sample to. Page 7. Line 58. You state that factors across different samples were similar. This is vague. Did you statistically analyse differences. If no significant differences exist, please state this. A supplementary file is suggested.

8 Reply: Methods, page 7, line The following changes have been made: The means of the explanatory factors were examined in the registry sample, the original NAAHS sample[3] and in the missing sample were carried out. We found no significant difference between the registry sample and the missing sample except for a slightly lower mean of negative life events in the missing sample (Supplement Table S1). The missing sample was not worse off. In addition, a new supplement table is provided. Page 8. Line 16. You do not need hyphens after sociodemographic and physical. Reply: This has been changed (page 7, lines 29 30). Changes described below Lines This sentence could be re-worded to improve clarity. Reply: This part of the data analysis section has been changed. Described below. Line 21. Throughout you use physical when I believe you are referring to musculoskeletal pain, sedentary activity and physical activity. Being more specific would assist in focusing the reader s mind. The following description of the statistical models in this paragraph is hard to follow the model building could be described in a more straight-forward way. Reply: Methods, page 7, lines and page 8, lines The data analysis section has been changed: Hierarchical logistic regression was used for the multivariable analysis for later mental health care use (Table 3). In Step 1 the sociodemographic (Model 1), physical factors (Model 2: musculoskeletal pain, adjusted for sedentary and physical activity) and psychosocial factors (Model 3, 4 and 5) were analyzed grouped together in models based on their respective characteristic groups. Insignificant factors were not included in the next steps in order to simplify the models. In Step 2, the significant sociodemographic factors from Model 1 were added as adjustments for musculoskeletal pain alongside physical activity (Model 6). The significant psychosocial factors from Step 1 were analyzed together in Model 7. In the final model, the significant psychosocial factors from the second step (Model 7) were added to the adjustment of adolescent musculoskeletal pain. Hierarchical logistic regression was used for the multivariable analyses on the diagnostic groups of mental health disorders (Table 4), following the same model building approach as described

9 above. However, only the significant factors from Step 1 in the mental healthcare use model were examined in order to simplify the models. In addition, musculoskeletal pain, physical activity and the sociodemographic factors were included in the final model regardless of if they were found insignificant in Step 1 and 2 (Model 1, 2 and 6), while insignificant psychosocial factors from Model 7 were excluded. P10. Table 1. You do not provide reference categories in the table. Please include, or at least make clear what the odds ratio refers to when it is not apparent, e.g. rather than gender use female. Reply: Gender has been changed into female gender in tables 3 and 4 (revised manuscript, page 12 and 14) P11. Line 10. You state that musculoskeletal pain lost its significance in the final (fully adjusted model). This makes me question the title of the paper. Reply: Results, page 13, lines 4 5. Following changes: However, when we adjusted for psychosocial factors in the final model, then musculoskeletal pain was no longer significantly associated with mental health care use in young adulthood. New title: The relationship between multisite musculoskeletal pain in adolescence and mental health disorders in young adulthood The NAAHS cohort study. P12. Line 54. The amount of variance explained is quite low and could be random noise. Please provide justification for the validity of the models. Reply: Looking at the number alone (highest, 10.0% explained variance with 6 predictors), then yes. However, the question of whether the explained variance is low or high is a relative question and depends on the nature of the associations one is examining. As most comparable research does not report the explained variance it is difficult to compare our results with others. Most likely their explained variances would be fairly similar.

10 However, the risk factors of mental health disorders are many and complex. In outcomes with multiple determinants the magnitude of measures of explained variance is limited by nature. In addition, due to the timeframe of the study, unmeasured factors or events from adolescence and young adulthood could contribute to the debut of mental health disorders. As in other psychological studies we did not expect the explained variance to be very high. However, the dose-response relationship presented in Table 2 and figure 1 strengthens the argument of a relationship between adolescent pain and later mental health care use and disorders. To compare with other fields, an example from cardiovascular risk factor research: The explained variance of self-reported physical activity was 6% for BMI and 7% for serum cholesterol in Aires et al. study (Eur J Epidemiol. 2003;18(6):479-85). ( References [3 5]: 3 Abelson RP. A Variance Explanation Paradox: When a Little is a Lot. Psychol Bull 1985;97: doi: / Fichman M. Variance Explained: Why Size Does Not (Always) Matter. Res Organ Behav 1999;21: O Grady KE. Measures of explained variance: Cautions and limitations. Psychol Bull 1982;92: doi: / The following has been added to the strengths and limitations part of the discussion, page 18, lines 9 12: At first glance the explained variance of the multivariable models might be considered to be low, however explained variance is a relative value, dependent on the nature of the associations examined. In outcomes with multiple determinants the size of the explained variance is limited by nature[45]. P13 Line 20 This association was confounded by psychosocial problems, not by other physical factors. Does this mean the relationship was not confounded by sedentary or physical activity? If so, please be specific. Reply: Discussion, page 15, lines The following changes were made: Overall, this association was mediated by adolescent psychosocial problems, not by physical or sedentary activity. However, adolescent musculoskeletal pain was associated with later anxiety disorder, when adjusted for adolescent psychosocial problems. Line 31.

11 the relationship between adolescent musculoskeletal pain and later mental health problems was confounded by adolescent psychosocial problems. This recurrent message makes me question the association in the title. Have you considered psychosocial factors as different type of variable, at least conceptually, e.g. mediators or moderators of the relationship? A discussion of this literature, and a theoretical explanation of the confounding relationship would strengthen your argument. Reply: The title has been changed. The relationship between pain and psychosocial problems is complex and a two-way street. Therefore, we have changed the term confounders to mediators, which may be more appropriate. REVIEWER REVIEW RETURNED GENERAL COMMENTS VERSION 2 REVIEW Daniel Whibley Epidemiology Group, University of Aberdeen, Scotland, UK 25-Apr-2016 Thank you for making amendments to your manuscript following my previous comments. Overall I think that the manuscript is much improved. There are, however, a number of points that I believe still require attention. Abstract (p 2 of 66, line 11): Please change a school-based survey responded by, to a school-based survey responded to by Abstract (p 2 of 66, line 12): 3987/5877 is 68%, not 70%. Is this an error, or are you using a different denominator? Abstract (p 2 of 66, line 20): You have not undertaken a mediation analysis so it is misleading to state that the relationship was mediated. The relationship may also be confounded. I think it is better to err on the conservative side, for example: the association was attenuated after controlling for adolescent psychosocial and mental health problems this could be due to confounding, however, a mediating role is also a possibility. Introduction (p4 of 66, line 14): Change is an important sign, to are an important sign. (I would actually prefer may be an important sign ). Methods (p 5 of 66, line 26): Please check 70% should not, in fact, be 68%. Methods (p 5 of 66, line 30): Please check 30% should not, in fact, be 32%. Data analysis (p 8 of 66, line 16): the missing sample. This is misleading if you were able to calculate values for a missing sample then they are not actually missing. I would change this to something along the lines of the population estimate derived from the NPR. Data analysis (p 8 of 66, line 32): I would change Insignificant factors to Factors that were not statistically significant at a predefined cut-off of p<0.05. I realise that you mention the significance

12 REVIEWER REVIEW RETURNED GENERAL COMMENTS level at the end of this section I suggest moving it here. Table 2 (p 11 of 66, line 12): You have a capital N for males with 2 sites of pain. You use a lower case n in all other instances. Make this lower case too. (Also I don t think you need to repeat females and males on lines 10 and 12 respectively just (%) would be fine.) Discussion (p 16 of 66, line 18): the association was mediated. You cannot discern this type of relationship from your analysis. As I have suggested for the abstract, something along the lines of the association was attenuated after controlling for adolescent psychosocial and mental health problems this could be due to confounding, however, a mediating role is also a possibility. Certainly, as you have stated, the relationship is most likely intertwined. Methodological strengths and limitations (p 18 of 66, line 20): high participation rate and a representative values. You do not need the a before representative values. Soumitri Sil Emory University, USA 06-Sep-2016 Thank you for the opportunity to review this manuscript, which focused on understanding whether multisite musculoskeletal pain during adolescence predicted mental health use and disorders in young adulthood. I have a few major concerns that dampen the potential contribution of this manuscript to the field. Major Concerns: - Many of the variables/measures used lack any definite time frame for response or validation by use in other studies. Although the authors discuss this as a limitation, the manuscript would be strengthened by using only measures that have evidence of acceptable psychometric properties and validation in other studies - Please clarify the final sample size used in analyses. It is difficult to understand the sample characteristics when different n s are used for all of the analyses. - It is inaccurate to state that any of the variables were mediators because no formal mediation testing was conducted. Rather it appears more accurate to state that the analyses controlled for other predictors. This needs to be addressed throughout the manuscript. Any significant findings should be discussed in terms of being "above and beyond" the effects of other psychosocial variables. - The discussion should more accurately highlight the findings in that pain was predictive of anxiety in young adulthood, especially since multiside pain did not significantly predict mental healthcare use in young adulthood. Additional minor concerns are listed below. Strengths and limitations - Psychosomatic is not synonymous with psychosocial Introduction

13 Reviewer: 1 - Daniel Whibley Dear Authors, - Please clarify the 3rd aim. What variables are being explored in the prediction of different mental health disorders? Methods - It is unclear what you mean by 30% nonresponders. Exactly who are these individuals? - There is an overlap in coding of lower university degree (up to 5 years) and higher university (more than 4 years) - What is the likelihood of someone receiving mental healthcare services and not being captured by the registry? - Do private specialists include psychiatrists only or psychologists and licensed counselors? Data analysis - Please clarify what the missing sample is Results - Please clarify what is meant by page 10 lines (few of the undiagnosed.) - In the final model, musculoskeletal pain did not predict mental healthcare use in young adulthood, yet this is highlighted as the primary finding of the paper Discussion - Pg 17 lines 25, please clarify whose findings you are referring - The summary of the main findings are misleading, given that the final model did not result in pain as a significant predictior of mental healthcare use above and beyond anxiety/depressive symptoms. VERSION 2 AUTHOR RESPONSE Thank you for making amendments to your manuscript following my previous comments. Overall I think that the manuscript is much improved. There are, however, a number of points that I believe still require attention. 1. Abstract (p 2 of 66, line 11): Please change a school-based survey responded by, to a schoolbased survey responded to by - Changed abstract in accordance to journal requirements. See new abstract. 2. Abstract (p 2 of 66, line 12): 3987/5877 is 68%, not 70%. Is this an error, or are you using a different denominator? - Corrected. 3. Abstract (p 2 of 66, line 20): You have not undertaken a mediation analysis so it is misleading to state that the relationship was mediated. The relationship may also be confounded. I think it is better to err on the conservative side, for example: the association was attenuated after controlling for adolescent psychosocial and mental health problems this could be due to confounding, however, a mediating role is also a possibility. - Changed to: Overall, the association between musculoskeletal pain and later mental health problems was attenuated after controlling for adolescent psychosocial and mental health problems, not by physical or sedentary activity. This could be due to confounding or mediation. 4. Introduction (p4 of 66, line 14): Change is an important sign, to are an important sign. (I would actually prefer may be an important sign ).

14 - Agreed, changed to may be an important sign. 5. Methods (p 5 of 66, line 26): Please check 70% should not, in fact, be 68%. - Corrected. 6. Methods (p 5 of 66, line 30): Please check 30% should not, in fact, be 32%. - Corrected. 7. Data analysis (p 8 of 66, line 16): the missing sample. This is misleading if you were able to calculate values for a missing sample then they are not actually missing. I would change this to something along the lines of the population estimate derived from the NPR. - Agreed. Changed to: the participants not accepting the registry linkage (non-registry sample). Labeling them the non-registry sample. Changed the supplement table. 8. Data analysis (p 8 of 66, line 32): I would change Insignificant factors to Factors that were not statistically significant at a pre-defined cut-off of p<0.05. I realise that you mention the significance level at the end of this section I suggest moving it here. - Agreed. Changed to: Factors that were not statistically significant, at a pre-defined cut-off of p<.05, were not included in the next steps in order to simplify the models. 9. Table 2 (p 11 of 66, line 12): You have a capital N for males with 2 sites of pain. You use a lower case n in all other instances. Make this lower case too. (Also I don t think you need to repeat females and males on lines 10 and 12 respectively just (%) would be fine.) - Changed. See table Discussion (p 16 of 66, line 18): the association was mediated. You cannot discern this type of relationship from your analysis. As I have suggested for the abstract, something along the lines of the association was attenuated after controlling for adolescent psychosocial and mental health problems this could be due to confounding, however, a mediating role is also a possibility. Certainly, as you have stated, the relationship is most likely intertwined. - Agreed, changed in accordance with the suggestions: However, the relationship between adolescent musculoskeletal pain and later mental health problems was attenuated after controlling for adolescent psychosocial and mental health problems. This could be due to confounding or mediating effects, indicating an intertwined relationship between adolescent psychosocial problems and musculoskeletal pain in predicting mental health problems. 11. Methodological strengths and limitations (p 18 of 66, line 20): high participation rate and a representative values. You do not need the a before representative values. - Changed to just: The study had equal gender distribution and a high participation rate. Reviewer: 2 - Soumitri Sil Thank you for the opportunity to review this manuscript, which focused on understanding whether multisite musculoskeletal pain during adolescence predicted mental health use and disorders in young adulthood. I have a few major concerns that dampen the potential contribution of this manuscript to the field. Major Concerns: 1. Many of the variables/measures used lack any definite time frame for response or validation by use in other studies. Although the authors discuss this as a limitation, the manuscript would be strengthened by using only measures that have evidence of acceptable psychometric properties and validation in other studies - The self-reported instruments in the adolescent study are a weakness, which was mentioned as limitations in the discussion. We are truly sorry and apologize for this, but it was no fault of the authors. Regretfully, the psychosocial factor scales did not have any time frame in the original study, thus not mentioned in the manuscript. Still, these factors are used for adjustment purposes and in spite of their weaknesses we do not feel that they are useless. - Our main defense is that we had a unique opportunity to adjust for several important adolescent

15 psychosocial aspects trying to show a more whole model. This came at the risk of over adjustment, therefore we show the adjustments in hierarchical models so the changes are transparent to the reader. We feel that the findings are important and outweighs the weaknesses. - The measures used have previously been found associated with adolescent musculoskeletal pain by us and other studies. 2. Please clarify the final sample size used in analyses. It is difficult to understand the sample characteristics when different n s are used for all of the analyses. - We have added a final model n to the table legend for table 3 and It is inaccurate to state that any of the variables were mediators because no formal mediation testing was conducted. Rather it appears more accurate to state that the analyses controlled for other predictors. This needs to be addressed throughout the manuscript. Any significant findings should be discussed in terms of being "above and beyond" the effects of other psychosocial variables. - See changes described above in response to reviewer 1. - We have conducted formal mediation analyses by PROCESS (Hayes 2013) for SPSS. However, for most of the adolescent factors it was not possible to say whether they appeared before or after the adolescent musculoskeletal pain. This makes it difficult to disentangle whether the adolescent psychosocial factors are confounders or mediators, due to this time sequence issue. Therefore, these analyses do not bring us much closer to any potential truth. Even though, we found significant findings the significant mediators are only potential mediators due to the time sequence issue described. Mediation analyses supplied below: Table The potential mediating effect of adolescent psychosocial factors on the relationship between adolescent musculoskeletal pain and mental health problems in young adulthood Mediation of later mental healthcare use Indirect effects of psychosocial factors OR CI Sobel test (Z-score) Univariate analyses: Self-efficacy , p<0.001 School-related stress , p<0.001 Negative life events , p<0.001 Anxiety/depression , p<0.001 Multivariable analysis: Self-efficacy , p=0.037

16 School-related stress , p=0.005 Negative life events , p=0.023 Anxiety/depression , p<0.001 Note: Mediation analyses conducted with PROCESS by Hayes (2013) for SPSS, bootstrap 1000, 95% CI. Data: Odds ratio and Sobel test. All analyses adjusted for gender. Total effect of adolescent musculoskeletal pain on later mental health problems when adjusted for gender: OR=1.27 (1.18, 1.37). Comment: Supplement Table S2 shows the mediation analyses and the indirect effects of the psychosocial factors on the relationship between adolescent musculoskeletal pain and mental health problems in young adulthood. The four psychosocial factors included in the final model of Table 3 were all potential mediators. - This could be included as a supplement table if the journal editor desires. However, as mentioned, they are just potential mediators and this point is already highlighted in the hierarchical design of the multivariable models. 4. The discussion should more accurately highlight the findings in that pain was predictive of anxiety in young adulthood, especially since multiside pain did not significantly predict mental healthcare use in young adulthood. - This is highlighted in the abstract and main findings part of the discussion. However, due to the risk of over-adjustment bias and the most likely intertwined relationship between pain and psychosocial factors in adolescence we do not want to just highlight the anxiety disorder findings. - A statement about over-adjustment risk has been added to the strengths and limitations section of the discussion: For most of the adolescent factors it was not possible to say whether they appeared before or after the adolescent musculoskeletal pain. This makes it difficult to decipher whether the adolescent psychosocial factors are confounders or mediators. If mediators the multivariable models are at risk of over-adjustment bias. Additional minor concerns are listed below. Strengths and limitations 5. Psychosomatic is not synonymous with psychosocial - Agreed. However, we do not mean psychosocial and we have difficulties seeing what else to Introduction 6. Please clarify the 3rd aim. What variables are being explored in the prediction of different mental health disorders? - Following changes made: Thirdly, we wanted to explore differences in the potential association between adolescent musculoskeletal pain and different mental health disorders. Methods

17 7. It is unclear what you mean by 30% nonresponders. Exactly who are these individuals? - See changes described above. In order to avoid confusion the following changes has been made: In order to explore the representativeness of the proportion of mental healthcare users in our sample (68% of the total population), the NPR calculated 8. There is an overlap in coding of lower university degree (up to 5 years) and higher university (more than 4 years) - Just a confusing labelling made by the national education registry. Up to 5 means 4 year or less, and more than 4 years means 5 years or more. Coding checked. Changed higher university degree to (5 years or more) to avoid confusion. 9. What is the likelihood of someone receiving mental healthcare services and not being captured by the registry? - The likelihood should be close to zero, however it is of course unknown. All parts of the Norwegian healthcare, including private specialists and centers, are required to send information to the NPR electronically 3 or 4 times per year. And they are closely checked. Of course some can be registered without a Norwegian citizen number, however that is a minor issue (see figure 1 (unfortunately in Norwegian) - And the adolescents in this study have a Norwegian birth number so the likelihood of not being captured by the registry in the years 2008 and onwards are small. And as mentioned we found few logical errors in the data we received (strengths and limitations). 10. Do private specialists include psychiatrists only or psychologists and licensed counselors? - It includes all public and private psychiatrist and psychologist working with mental healthcare in Norway. Described in the methods under mental healthcare registry Data analysis 11. Please clarify what the missing sample is - See changes described above in response to reviewers 1. Results 12. Please clarify what is meant by page 10 lines (few of the undiagnosed.) - Made some additional clarifications that we hope are helpful: Few of the undiagnosed participants (n=9) were at risk of remaining undiagnosed due being evaluated only at the end of the registration period (the last three months). 13. In the final model, musculoskeletal pain did not predict mental healthcare use in young adulthood, yet this is highlighted as the primary finding of the paper - See comments above referring to the changes made to the abstract and the main findings section in the discussion. Discussion 14. Pg 17 lines 25, please clarify whose findings you are referring - Here we are uncertain about the comment. The specified section refers to the description of the NPR data we received (methodological strengths and limitations). We are referring to our own findings. 15. The summary of the main findings are misleading, given that the final model did not result in pain as a significant predictior of mental healthcare use above and beyond anxiety/depressive symptoms. - See comments above referring to the changes made to the abstract and the main findings section in the discussion.