Attention and Self-Control Dimensions of Impulsivity Predict the Quality of Life among Male Patients Seeking Treatment for Alcohol Use Disorder: The Mediating Role of Anxiety and Severity of Alcohol Use Disorder

Comment: Reviewer 1: Comments 1: This study evaluated predictors of QOF among alcoholic patients in treatment. The study is nicely done, considering that the number of subjects was quite limited.Reply: Thank you for your comments and suggestions on our manuscript. We appreciate your thorough review and will address each of your points below: Comment 2: The image quality was poor, please improve them.Reply: We have carefully considered your comment regarding the image quality and addressed this concern in the revised version of the manuscript. Comment 3: As the authors partially addressed, the age of onset of alcoholism is highly related to the impulsivity and the personality and temperament traits of alcoholic subject. That then is relevant for how the alcoholic patient views the treatment. As a rule of thumb, early-onset alcoholics are not motivated for treatment, whereas late-onset alcoholics are. It can also be argued that what drives those alcoholics to drink is very different. Late-onset alcoholism is related not only to less impulsivity and diminished reward system function, but also to increased anxiety. Very different underlying neurochemistry. Now, the most important participant data (scores) should be blotted against their age, to show it there are clusters or non-linearity in the data, as the average age was about 37 years, probably including both early and late-onset alcoholics.Reply: We have addressed this concern in the revised version of the manuscript as follows:“The mean age of onset of alcohol use was found to be 20.11 years with a standard deviation of 5.33. Among the participants, 59.1% (52 individuals) reported an onset of alcohol use at the age of 20 or younger, while 40.9% (36 individuals) initiated alcohol use at an age older than 20. However, it is important to note that our study did not find a significant correlation between the age of onset of alcohol use and impulsivity”. [line 396-399]We have incorporated this particular finding into correlation table 3 to enhance comprehension”.[ Table 3,Serial No 16] About methods:Comment 4; how was multiple testing adjusted? When performing multiple analyses, the random findings may occur.Reply: We have rephrased the sentences previously mentioned in statistical methods to enhance clarity as follows: “Multiple linear regression analysis was performed to examine the relationship between independent variables and Quality of Life (QoL). Variables that exhibited a p-value of less than 0.2 during the initial unadjusted analysis were simultaneously entered into the model using the "enter" method , and unstandardized beta coefficients were estimated”.  [ Line 290-293] Comment 5: The mediation analysis was performed using *which* PROCESS Macro? Number 4?Reply: Thank you for your attention. Yes, the mediation analysis was conducted using PROCESS Macro –Model 4, and it has also been included in the revised manuscript.  Reviewer 2 General comments:Comment 1. A review of the paper is necessary to correct typographical errors, especially missing spaces or extra spaces.Reply: Thank you for bringing this matter to our attention. We are dedicated to this endeavor, aiming to eradicate every single spelling, grammar, and punctuation error within manuscripts.  Comment 2. Abbreviations should be reviewed. Avoid using the complete expression f when it was described previously in the text.Reply: Thank you for taking the time to review our manuscript, and we greatly appreciate your valuable feedback. We have addressed the concern regarding the use of abbreviations in the revised version of the manuscript.Methods:Comment 1.Line 130-143: long description of the center which is unnecessary. Reply: We appreciate your input and have taken your concerns about the lengthy description of the center . In response, we have made substantial revisions to the manuscript, condensing the center's description and eliminating unnecessary details to ensure a more concise and focused presentation. Comment 2. A description of the recruitment of the control group is needed.Reply: we have added in revised manuscript: “We recruited healthy controls who were matched with the study subjects in terms of age, sex, and socioeconomic status. Exclusion criteria were as follows: current or past psychiatric disorders, any substance use disorders other than nicotine, co-morbid chronic physical illnesses, and AUDIT scores of 8 or higher. These control subjects were selected from the same neighborhoods or from within the close circle of friends of our study cases, ensuring a suitable comparison group for the study”[line 170-175].   Comment 3. Line 149-152 wrong enumeration.Reply: Thank you for your feedback. We've made the necessary corrections in the revised manuscript. Comment 4. Line 163: Which unit was used? Reply: We measured the quantity of alcohol using a “standard drink”, which is equal to 10 grams of pure alcohol, as suggested by the WHO AUDIT guidelines. These changes have been added to the updated manuscript.  Comment 5. Point 2.4.: References to the versions of every instrument used are needed. Also references to the psychometrics cited in the text.Reply: In the revised manuscript, we have included references to the original and important versions of the tools we used. Results: Comment 1. Add clinical variables mentioned in point 2.3.Procedure to Table 1.Reply: The clinical details mentioned in section 2.3 (the Procedure) have already been covered in Table 3, which shows Descriptive Statistics and the Correlation Matrix of the study variables. It would be repetitive to include them again in Table 1, as Table 3 already has all the necessary information about these variables. Comment 2. Table 1: Highlight statistical significance and maintain the same format in all tables.Reply: Thank you for your feedback. We've made the necessary corrections in the revised manuscript. Comment 3. Line 283-284: could be improved in their wordingReply: As reviewer suggested, we have rephrased the lines in the revised manuscript to make them clearer and easier to understand. “The study was conducted in accordance with the Declaration of Helsinki, and the study was approved by the Ethics Committee, All India Institute of Medical Sciences, New Delhi”[line 333-335] Comment 4. Line 322-323: not necessaryReply : As the reviewer recommended, we've taken out some sentences from the updated manuscript to make it simpler and easier to grasp. Comment 5. Line 323-326 belongs to the Methods section.Reply: As the reviewer suggested, we've taken lines 323 to 326 and moved them to the Methods section in the revised manuscript. Comment 6. Lines 380-384 belong to the Discussion section.Reply: As the reviewer suggested, we've taken lines 380 to 384 and moved them to the discussion section in the revised manuscript.[lines: 550-558] Comment 7. Lines 358-360 would be more useful and clear if were combined with the next paragraph in line 369.Reply : As the reviewer suggested ,Lines 358-36 were combined with the next paragraph in line 369. Comment 8. Lines 413-417 belong to the Discussion section. Rely: As the reviewer suggested, we've taken lines 413 to 417 and moved them to the discussion section in the revised manuscript.[lines: 559-566]  Discussion Comment: Line 466: Healthy controls do not consume any alcohol or do they haven't an AUD diagnosis? Reply:. We recruited healthy controls who were matched with the study subjects in terms of age, sex, and socioeconomic status. Exclusion criteria were as follows: current or past psychiatric disorders, any substance use disorders other than nicotine, co-morbid chronic physical illnesses, and AUDIT scores of 8 or higher. The participants in the study did not have a diagnosis of Alcohol Use Disorder (AUD), and their scores on the Alcohol Use Disorders Identification Test (AUDIT) fell within the range of 0 to 7.  Comment 2. Line 497: Reference is needed.  Reply: We've added the reference number 13. Reviewer 3:  “Attention and Self-Control Dimensions of Impulsivity Predict the Quality of Life among Male Patients Seeking Treatment for Alcohol Use Disorder: The Mediating Role of Anxiety and Severity of Alcohol Use Disorder”（ behavsci-2597201）Comment 1. The data about alcohol consumption need to be updated, and considering that the current investigation was conducted during COVID-19，the data about alcohol consumption during COVID-19 should also be included. The following papers might be useful. GBD 2020 Alcohol Collaborators. Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020. Lancet. 2022 Jul 16;400(10347):185-235. doi: 10.1016/S0140-6736(22)00847-9.  Acuff, S. F., Strickland, J. C., Tucker, J. A., & Murphy, J. G. (2022). Changes in alcohol use during COVID-19 and associations with contextual and individual difference variables: A systematic review and meta-analysis. Psychology of Addictive Behaviors, 36(1), 1–19. https://doi.org/10.1037/adb0000796 Sohi, I., Chrystoja, B.R., Rehm, J., Wells, S., Monteiro, M., Ali, S. et al. (2022) Changes in alcohol use during the COVID-19 pandemic and previous pandemics: A systematic review. Alcoholism: Clinical and Experimental Research, 46, 498–513. Available from: https://doi.org/10.1111/acer.14792 Reply: We would like to clarify that there was a typographical error in our previous communication regarding the study duration .The correct timeframe for the recruitment of “participants in this study spans from December 2018 to June 2020”[line 157-158]. We apologize for any confusion caused by our earlier statement, which incorrectly stated the year as 2019 instead of 2018. To clarify further, patient recruitment commenced in December 2018 and concluded with data collection in March 2020, all prior to the imposition of COVID-19 restrictions. The remaining data processing and analysis were finalized over the subsequent three months, culminating in June 2020. It is important to note that all study participants were recruited before the COVID-19 pandemic restrictions were imposed in India, which commenced on April 20, 2020, for the first time. Therefore, the study was not affected by these restrictions. Furthermore, we would like to mention that this study received funding from the Department of Science & Technology, Government of India, under the Cognitive Science Research Initiative (CSRI), with funds approved in 2017, as indicated by approval number DST/CSRI/2017/149. However, in response to the reviewer's feedback and their emphasis on updating the data, we diligently incorporated the latest information on alcohol consumption in brief, as recommended. “In the year 2020, 1.03 billion males and 312 million females worldwide consumed harmful amounts of alcohol in excess of the non-drinker equivalence (NDE) and contributing to a total of 1.78 million deaths in the same year. Notably, alcohol consumption emerged as the primary risk factor for mortality among males aged 15–49 years” [ line 41-45  ]  Comment 2. About the impulsivity and Alcohol Use Disorder, the following papers need to be reviewed and discussed. And especially on the previous findings about the Multidimensionality in impulsivity and alcohol use and identify clearly the current research gaps. Rick A. Stephan, Omar M. Alhassoon, Kenneth E. Allen, Scott C. Wollman, Matt Hall, William J. Thomas, Julia M. Gamboa, Chrissy Kimmel, Mark Stern, Celina Sari, Constance J. Dalenberg, Scott F. Sorg & Igor Grant (2017) Meta-analyses of clinical neuropsychological tests of executive dysfunction and impulsivity in alcohol use disorder, The American Journal of Drug and Alcohol Abuse, 43:1, 24-43, DOI: 1080/00952990.2016.1206113 Kovács I, Demeter I, Janka Z, Demetrovics Z, Maraz A, Andó B (2020) Different aspects of impulsivity in chronic alcohol use disorder with and without comorbid problem gambling. PLoS ONE 15(1): e0227645. https://doi.org/10.1371/journal.pone.0227645 Hershberger AR, Um M, Cyders MA. The relationship between the UPPS-P impulsive personality traits and substance use psychotherapy outcomes: A meta-analysis. Drug Alcohol Depend. 2017 Sep 1;178:408-416. doi: 10.1016/j.drugalcdep.2017.05.032. Epub 2017 Jun 28. PMID: 28709080; PMCID: PMC5561735. Sliedrecht W, Roozen HG, Witkiewitz K, de Waart R, Dom G. The Association Between Impulsivity and Relapse in Patients With Alcohol Use Disorder: A Literature Review. Alcohol Alcohol. 2021 Oct 29;56(6):637-650. doi: 10.1093/alcalc/agaa132. PMID: 33382416. Reply: To address your comment, we have undertaken a thorough review of the suggested papers, as well as additional relevant literature in the field. We have tried to incorporate these findings into the manuscript to strengthen our discussion on impulsivity and its multidimensional aspects in the context of AUD.“Recent research suggests that impulsivity is a complex concept that can be viewed from different angles. It can be seen as a consistent personality trait or as a behavioral indicator of decision-making and actions. "Trait impulsivity" refers to a relatively stable form of impulsivity that is part of a person's character. This aspect is usually evaluated using self-report questionnaires. On the other hand, "behavioral impulsivity" refers to patterns of impulsive behavior, assessed through objective measurements in various situations, often involving tasks [24,25]. The Barratt Impulsiveness Scale (BIS) developed by Patton et al. (1995) [26], and the UPPS-P Impulsive Behavior Scale by Whiteside and Lynam (2001)[27], are self-report questionnaires used to assess impulsivity as a personality trait. These scales also identify various subcategories of impulsive traits through specific subsections. People with alcohol use disorder score higher on BIS compared to those without the disorder [28,29]. Earlier research has demonstrated a positive link between trait impulsivity and alcohol consumption.[lines 101-102] Studies have also indicated bidirectional relationship   between impulsivity and alcohol use  Individuals diagnosed with alcohol use disorder (AUD) who also exhibit comorbid gambling symptoms were found to have elevated levels of trait impulsivity and a propensity for non-planning behaviors. Interestingly, this association remains significant irrespective of factors such as intelligence, age, and psychopathological symptoms [lines 103-107].  Impulsivity appears to play a significant role in the onset and progression of substance use disorder, either as an underlying susceptibility or as a result of prolonged substance abuse [33]. Moreover, there is evidence indicating that alcohol can potentially influence impulsivity patterns as time goes on [34]. Moreover, it has been observed that all three facets of impulsivity, encompassing 'trait impulsivity,' 'motor impulsivity,' and 'impulsive choice impulsivity,' are associated with AUD relapse  Cognitive-behavioral therapies focused on addressing impulsivity have the potential to augment individuals' ability to manage their alcohol consumption, thereby resulting in enhanced treatment outcomes. However, the absence of premeditation and the presence of high negative urgency have been associated with less favorable results in psychotherapy for Substance Use Disorder (SUD).[lines 111-118]  Comment 3. Why did you choose anxiety and Severity of Alcohol Use Disorder as mediators need to be justified in the introduction? The following paper might be useful. Why did you measure depression Did you try to treat depression as a potential mediator？  Vera, B.d.V.; Carmona-Márquez, J.; Lozano-Rojas, Ó.M.; Parrado-González, A.; Vidal-Giné, C.; Pautassi, R.M.; Fernández-Calderón, F. Changes in Alcohol Use during the COVID-19 Pandemic among Young Adults: The Prospective Effect of Anxiety and Depression. J. Clin. Med. 2021, 10, 4468. https://doi.org/10.3390/jcm10194468 Luk JW, Stangl BL, Gunawan T, et al. Changes in alcohol-related behaviors and quality of life during the COVID-19 pandemic: impact of alcohol use disorder diagnosis and treatment history. J Clin Psychiatry. 2023;84(1):22br14462. Reply: Thank you for your valuable feedback and thoughtful questions regarding our research. We appreciate your input, and we addressed reviewer’s comments in detail below:Justification for Anxiety and Severity of Alcohol Use Disorder as Mediators: We acknowledge reviewer’s concern about the choice of anxiety and the severity of alcohol use disorder as potential mediators in our study. In the revised introduction, we provided a more comprehensive justification for selecting these variables as mediators. Specifically, we elaborated on their theoretical relevance to the research question and their demonstrated significance in previous literature. Additionally, we discussed the potential mechanisms through which anxiety and alcohol use disorder severity may mediate the relationship under investigation.Reference Suggestion: We appreciate the reference provided by reviewer and reviewed the suggested paper to ensure that our rationale aligns with the existing literature. We included relevant citations from this source to strengthen our argument in the introduction.Measurement of Depression as a Mediator: We did measure depression in our study, and we recognize that it could potentially serve as a predictor in adjusted multiple linear regression. In the revised introduction, we clarified our decision not to treat depression as a primary mediator. We discussed the theoretical and empirical reasons behind our choice to focus on anxiety and alcohol use disorder severity as primary mediators.  Comment  4. The following paper should be incorporated to discuss the current state of art about alcohol use in India. Heijdra Suasnabar, JM, Nadkarni, A, Palafox, B. Determinants of alcohol use among young males in two Indian states: A population-based study. Trop Med Int Health. 2023; 28(8): 660–676. https://doi.org/10.1111/tmi.13907  Reply: We appreciate the reference provided by reviewer and reviewed the suggested paper to ensure that our rationale aligns with the existing literature. We included relevant citations from this source to strengthen our argument in the discussion.“Moreover, it has been noted that several proximal factors are associated with regular alcohol consumption. These factors include emotional regulation and early tobacco use. Addressing these determinants could significantly aid in the management of individuals with AUD ”.[line 597-600] Comment 5.“Problematic alcohol use is associated with various health problems such as liver cirrhosis, cardiovascular diseases, mental disorders, and increased risks of accidents and injuries.”this statement needs references.Reply: we have added the relevant references in revised manuscript Comment 6. In the line 272-275 of Statistical analysis, did you know which variables should be treated as outcome, predictor and mediator before formal analysis？Reply: Multiple linear regression analysis was conducted to investigate the association between independent variables and Quality of Life (QoL). Variables with a p-value less than 0.2 in the initial unadjusted analysis were simultaneously entered into the model using the "Enter" method of SPPS to assess their predictive capabilities. Subsequently, a review of existing literature and an examination of the variables were conducted to determine whether they met the assumptions necessary for mediation analysis. Variables meeting these criteria were identified as potential mediators.Comment 7. How did you determine the sample size? Did you calculate the sample size needed before formal study? The current sample size seems too little to get reliable results.Reply: Thank you for your comment and concern about the sample size in our study. The determination of our sample size was carried out by our institute's biostatistical team, who carefully considered the available literature and statistical methodologies. Added as follows:“1.Assuming a pooled standard deviation of 3.95 units (raw score on WHOQOL- BREF scale for physical health domain ) and a design effect (DEFF) of 1.4, the study would require a sample size of: 83 for the test group (Individuals with alcohol use disorder)  and 42 for the control  group (i.e. a total sample size of 125; to ensure that the control group is 0.5 times larger than the test group) to achieve a power of 80% and a level of significance of 5% (two sided), for detecting a true difference in means between the test and the control  group of -2.5 (i.e. 21.45 - 23.95) units(raw score on WHOQOL- BREF scale for physical health domain ). Assuming a pooled standard deviation of 3.27 units (raw score on WHOQOL- BREF scale for Psychological domain ) and a design effect (DEFF) of 1.4, the study would require a sample size of: 84 for the test group and 42 for the reference group (i.e. a total sample size of 126; to ensure that the Reference group is 0.5 times larger than the test group) to achieve a power of 80% and a level of significance of 5% (two sided), for detecting a true difference in means between the test and the reference group of -2.05 (i.e. 18.39 - 20.44) units(raw score on WHOQOL- BREF scale for psychological domain ).Furthermore, we have conscientiously considered the recommendations regarding sample size, as put forth by Green (1991). Green's guidance suggests that for testing the multiple correlation, a sample size of N > 50 + 8m is advisable, with 'm' denoting the number of independent variables in question. This recommendation takes into account the expectation of a medium-sized relationshipWe chose to focus on the Physical Health and Psychological domains of the WHOQOL – BREF scale as our variables of interest, based on a comprehensive review of existing literature. Consequently, following these calculations, we arrived at a total of 88 participants for the test group and 44 for the control group.In our study analysis. We converted WHOQOL-BREF raw scores into transformed scores on a 0-100 scale”.[lines 303-330]Reference: Srivastava S, Bhatia MS. Quality of life as an outcome measure in the treatment of alcohol dependence. Ind Psychiatry J. 2013 Jan;22(1):41-6. doi: 10.4103/0972-6748.123617. PMID: 24459373; PMCID: PMC3895312.Green SB. How Many Subjects Does It Take To Do A Regression Analysis. Multivariate Behav Res. 1991 Jul 1;26(3):499-510. doi: 10.1207/s15327906mbr2603_7. PMID: 26776715. Comment 8. For all the scales and questionnaires, did you use the original version or the Indian Version？? If the latter is true, then the references about the original version and the Indian version should be properly cited.Reply: In the revised manuscript, we have included references to the original and important versions of the tools we used.Comment  9 & 10. For Socio-demographic variables in table 1, one column to include “Education”, 10.“ Employment Status”，“Family Type”and “Marital Status”should be added.Reply: Thank you for your attention. We have added one more column for Education”, Employment Status”，“Family Type” and “Marital Status” in table 1.Comment 11. Please provide the effect size where available in table 1.Reply: Thank you for your attention. It has been added in the revised manuscript.  Comment.12. “Live type” in table 2 is not appropriate. “Family type” might be a better choice.Reply: Thank you for your attention. It has been corrected in the revised manuscript. Comment 13. What does “2.4. Top of Form” mean？Reply: Thank you for your attention. The typographic error has been corrected in the revised manuscript Comment  14. “It's a quick and reliable test that gives you a total score and two smaller scores” what does “two smaller scores” mean?Reply: Thank you for your feedback. We've made the necessary corrections in the revised manuscript. The OCDS is a 14-item questionnaire. It is a widely used tool to measure cravings for alcohol. It's a quick and reliable test that gives you a total score and “two scores: one for the obsessive cravings (based on questions 1-6) and another for the compulsive cravings (based on questions 7-14)” [line 241-242] Comments 15. Why did you measure cognitive Function and self-efficacy?Reply: In our study, we assessed cognitive functions and self-efficacy to investigate the relationship between these factors and the quality of life among individuals with alcohol use disorder. Comment 16. COVID-19 should be included in the title.Reply: No, We would like to clarify that there was a typographical error in our previous communication regarding the study duration .The correct timeframe for the recruitment of participants in this study spans from December 2018 to June 2020. We apologize for any confusion caused by our earlier statement, which incorrectly stated the year as 2019 instead of 2018. To clarify further, patient recruitment commenced in December 2018 and concluded with data collection in March 2020, all prior to the imposition of COVID-19 restrictions. The remaining data processing and analysis were finalized over the subsequent three months, culminating in June 2020. It is important to note that all study participants were recruited before the COVID-19 pandemic restrictions were imposed in India, which commenced on April 20, 2020, for the first time. Therefore, the study was not affected by these restrictions.  Comment 17. I recommend that the paper be thoroughly proofread and edited for languages and grammars, to enhance readership.Reply: Thank you for bringing this matter to our attention. We are dedicated to this endeavor, aiming to eradicate every single spelling, grammar, and punctuation error within manuscripts Comment  18. A limitation part needs to be added at the end of the discussion part. The following papers might be useful. Lac, A. COVID-19 Stress (Traumatic Symptoms, Compulsive Checking, Xenophobia, and Danger & Contamination) and Alcohol Use Uniquely Explain State Alcohol Cravings. J Psychopathol Behav Assess 45, 537–548 (2023). https://doi.org/10.1007/s10862-023-10033-z Oliván-Blázquez, B., Lear-Claveras, A., Samper-Pardo, M. et al. Worsening of alcohol abuse disorder in a Spanish population during the first twelve months of the COVID-19 pandemic and associated factors: retrospective, ecological and community study. BMC Psychiatry 23, 504 (2023). https://doi.org/10.1186/s12888-023-04993-5Reply: In the revised manuscript, we have taken significant steps to enhance the clarity and address the concerns raised by the reviewers regarding the limitations of our study. To effectively tackle this issue, we have dedicated the final paragraph of the discussion section to highlight and elucidate the study's limitations. This approach not only ensures that the limitations are brought to the forefront for both the reviewers and readers but also demonstrates our commitment to transparency and rigorous research.“There are a few notable limitations associated with this research. Firstly, the use of a small sample size poses a significant constraint. Such small sample sizes can substantially diminish the statistical power of the study findings, necessitating a cautious interpretation of the results. Furthermore, the fact that this study was conducted at a single-center raises concerns about its representativeness for a broader population and more diverse settings. This limitation hampers the external validity and generalizability of the findings and requires a careful interpretation of the results. To mitigate these limitations, it is imperative that future research endeavors consider employing a larger sample size and adopting a multicentric approach. By doing so, researchers can bolster the statistical power of their studies, thereby enhancing the reliability and generalizability of the results. In conclusion, the path forward for future investigations in this area should involve a commitment to larger and more diverse samples, ultimately enabling a more comprehensive understanding of the subject matter”.[line 608-620]We would like to clarify that there was a typographical error in our previous communication regarding the study duration .The correct timeframe for the recruitment of participants in this study spans from December 2018 to June 2020. We apologize for any confusion caused by our earlier statement, which incorrectly stated the year as 2019 instead of 2018. To clarify further, patient recruitment commenced in December 2018 and concluded with data collection in March 2020, all prior to the imposition of COVID-19 restrictions. The remaining data processing and analysis were finalized over the subsequent three months, culminating in June 2020. It is important to note that all study participants were recruited before the COVID-19 pandemic restrictions were imposed in India, which commenced on April 20, 2020, for the first time. Therefore, the study was not affected by these restrictions.   Reviewer 4The manuscript contains data of interest on the relationship of attention and self-control dimensions of impulsivity in the Quality of life of male patients seeking treatment for alcohol use disorders. However, there are several conceptual and methodological aspects that the authors should review in depth:Comment 1- The diagnosis is confused with screening with MINI, finally how many of the 88 patients have a mild, moderate and severe alcohol use disorder according to the DSM-5 criteria? The use of the AUDIT is again a screening evaluation and not a diagnostic one. The exclusion criterion of “comorbid chronic illness” seems correct, but there is no mention of the comorbidity of mental disorders (dual disorders). It is necessary to make this information explicit since the influence on the results can be of enormous magnitude and even change the meaning of those obtained.Reply:  We have already  outlined in our inclusion criteria that the diagnosis of alcohol use disorder (AUD) was determined in accordance with DSM-5 criteria, utilizing the Mini-International Neuropsychiatric Interview (MINI) – Plus. The MINI-Plus is a structured and standardized diagnostic interview used to determine the most common psychiatric disorders according to  DSM-5.The MINI-Plus encompasses a wide range of psychiatric disorders, such as mood disorders (e.g., depression, bipolar disorder), anxiety disorders (e.g., panic disorder, social phobia), psychotic disorders (e.g., schizophrenia), substance use disorders (e.g., alcohol and drug abuse), eating disorders, and more. All participants met the criteria for severe alcohol use disorder as defined by DSM-5. It is important to note that the AUDIT was not utilized for diagnostic purposes.We have incorporated the following exclusion criteria: "Individuals with comorbid psychotic and bipolar disorders were excluded."Comment 2- What sense does it make to have considered the healthy controls (n = 44) that are presented in table 1 if they are not later included in the analyzes in a comparative way? They are not even mentioned in method. It would be appropriate to eliminate them and instead compare the data from the patient sample with the normative data from the different scales. Comparisons with t do not contain the effects. If the controls are maintained, all analyzes must be carried out for the two groups and conveniently compared.Reply: We made the necessary revisions to provide a comprehensive description of the control group recruitment process as follows: “We recruited healthy controls who were matched with the study subjects in terms of age, sex, and socioeconomic status. Exclusion criteria were as follows: current or past psychiatric disorders, any substance use disorders other than nicotine, co-morbid chronic physical illnesses, and AUDIT scores of 8 or higher. These control subjects were selected from the same neighborhoods or from within the close circle of friends of our study[ lines 170-175] Our intention in including the healthy controls was to establish a baseline for comparison with the patient sample, which we believe can provide valuable context for interpreting the results. Comment 3- In relation to the selected references, an attempt should be made to update them in a field of study in constant supply of data. Worldwide, polydrug use is more common than exclusively alcohol consumption in people seeking treatment. The data converge with those obtained in the present work and I suggest taking into consideration quality of life papers on substance use disorders that also consider and compare patients with dual disorders (Journal of Clinical Medicine, 2020, 9: 3110. doi: 10.3390/jcm9103110; Health and Quality of Life Outcomes, 2017, 15 (209). doi: 10.1186/s12955-017-0781-y).Reply: Thank you for your insightful comments and suggestions regarding our manuscript. We appreciate your feedback and value your expertise in the field of substance use disorders. We acknowledge the importance of keeping our references up-to-date, especially in a field like substance use disorders where new research emerges regularly. We made an effort to update our references to include more recent studies that reflect the current state of research in polydrug use and its prevalence among individuals seeking treatment. Comments 4- In procedure, information from the instruments is repeated (page 4), these should be described in a much more reduced way and instead include the internal reliability for the sample studied in the manuscript.Reply : We have implemented the required revisions as per the reviewer's suggestions.Comment 5- The correlations do not need to be shown and, in any case, with the sample size we are working with, we must be cautious and consider them only from the p-value of 0.01. It is sufficient to provide the data related to Table 4. Do the linear regressions meet the application criteria? Why have factors that influence all the variables studied, such as age, not been controlled?Reply: Multiple linear regression analysis was conducted to investigate the association between independent variables and Quality of Life (QoL). Variables with a p-value less than 0.2 in the initial unadjusted analysis were simultaneously entered into the model using the "Enter" method of SPSS to assess their predictive capabilities[lines: 290-293]Furthermore, we have conscientiously considered the recommendations regarding sample size, as put forth by Green (1991). Green's guidance suggests that for testing the multiple correlation, a sample size of N > 50 + 8m is advisable, with 'm' denoting the number of independent variables in question. This recommendation takes into account the expectation of a medium-sized relationship[ lines:319-323] Green (1991) presents a comprehensive examination of the procedures employed in determining sample sizes for regression analysis. He recommends a sample size of N > 50 + 8m, where 'm' represents the number of independent variables, when testing the multiple correlation, assuming a medium-sized relationship. In our study, we had only four independent variables in the physical domain as the outcome. Thus, the recommended sample size for this aspect of the study should be 82. For the multiple linear regression involving five independent variables with the psychological domain as the outcome variable, the total required sample size should be 90. It is worth noting that we correctly applied multiple linear regression to assess predictors for the outcome variables, in accordance with our research approach.Refrence: Green SB. How Many Subjects Does It Take To Do A Regression Analysis. Multivariate Behav Res. 1991 Jul 1;26(3):499-510. doi: 10.1207/s15327906mbr2603_7. PMID: 26776715.In the revised manuscript, we have taken significant steps to enhance the clarity and address the concerns raised by the reviewers regarding the limitations of our study. To effectively tackle this issue, we have dedicated the final paragraph of the discussion section to highlight and elucidate the study's limitations. This approach not only ensures that the limitations are brought to the forefront for both the reviewers and readers but also demonstrates our commitment to transparency and rigorous research.“There are a few notable limitations associated with this research. Firstly, the use of a small sample size poses a significant constraint. Such small sample sizes can substantially diminish the statistical power of the study findings, necessitating a cautious interpretation of the results. Furthermore, the fact that this study was conducted at a single-center raises concerns about its representativeness for a broader population and more diverse settings. This limitation hampers the external validity and generalizability of the findings and requires a careful interpretation of the results. To mitigate these limitations, it is imperative that future research endeavors consider employing a larger sample size and adopting a multicentric approach. By doing so, researchers can bolster the statistical power of their studies, thereby enhancing the reliability and generalizability of the results. In conclusion, the path forward for future investigations in this area should involve a commitment to larger and more diverse samples, ultimately enabling a more comprehensive understanding of the subject matter”.[line 600-613] Comment 6 - The term “prediction” should be avoided in the title and in the text, since the analyzes only establish relationships or associations.Reply: Multiple linear regression analysis was conducted to investigate the association between independent variables and Quality of Life (QoL). Variables with a p-value less than 0.2 in the initial unadjusted analysis were simultaneously entered into the model using the "Enter" method of SPSS to assess their predictive capabilities. This study used a valid prediction model, thus making the inclusion of the term "prediction" in the manuscript appropriate. Comment 7- The discussion is excessively extensive because in many cases the results are repeated. Emphasis is also placed on sociodemographic data that do not come from an epidemiological study to give them such importance.Reply:  We acknowledge your point about the discussion being excessively lengthy and potentially repetitive. We revised the discussion section to streamline it and eliminated any unnecessary repetition. We understand your concern regarding the emphasis on sociodemographic data in our discussion. Our intention was to provide a comprehensive context for our study results. We made the necessary revisions as suggested and ensure that the revised discussion section is more concise, focused on epidemiological data, and adds value to the overall understanding of our research. Thanks