ABSTRACT
The relationship between depression and alcohol consumption has not yet been confirmed, and no large‐scale studies have examined this association in Asian college students. This study examined the correlation between excessive drinking and depression in Japanese college students. We solicited the participation of undergraduate and graduate students aged 20 years or older who underwent annual health examinations between April 2019 and January 2020 at two universities in Japan. A self‐administered questionnaire was used to assess the frequency of alcohol drinking, the amount of alcohol consumed per day, binge drinking during the past month, Center for Epidemiologic Studies Depression Scale score, and demographic data. A total of 4535 students were analyzed, specifically 2775 men (61.2%) and 1760 women (38.8%). Of these, 1076 men (66.3%) and 548 women (33.7%) were classified as excessive drinkers. Further, 1474 students (32.5%) had depression, of whom 528 (35.8%) were excessive drinkers. In a logistic regression analysis, depression was found to be inversely associated with heavy drinking (odds ratio 0.59 [0.36–0.98]), even after adjusting for several variables. This study found a negative association between excessive alcohol use and depression among Asian college students. More detailed research should investigate the relationship between alcohol consumption and depression by age group and race.
Keywords: binge drinking, college students, depression, heavy drinking, mental health
A large‐scale study of 4535 Japanese college students found a negative association between depression and excessive alcohol use. Surprisingly, those who drank excessively were less likely to be depressed.
1. Introduction
Depression is a major global public health challenge [1]. The Institute for Health Metrics and Evaluation reported that depression is the 12th leading contributor to global disability‐adjusted life years, and causes the second highest number of years lost due to disability [2]. Thus, depression caused economic losses of $5 trillion in 2019 [3].
Alcohol binge drinking is a modifiable behavior that is considered a risk for depression. Various studies have examined the relationship between depression and alcohol consumption, but the results are inconsistent [4]. A previous study found that alcohol use disorders increased the risk of depression, not the other way around, and that metabolic changes resulting from alcohol exposure affected this causal relationship [4]. An analysis of the data from a large‐scale study in the United States indicated a significant lifelong association between alcohol use disorders and depression, even after controlling for a wide range of sociodemographic factors, other psychiatric factors, and substance use disorder [5]. Furthermore, studies using longitudinal data showed a significant association between high levels of alcohol consumption and depression scores, even after adjusting for various characteristics [6]. Li et al. conducted a systematic review of the effect of alcohol use disorders and alcohol intake on the risk of subsequent depression, and found that these symptoms were associated with alcohol use disorders but not binge drinking [7].
In contrast, another study observed a negative association between moderate alcohol use and depression, albeit with inadequate adjustment for confounders [8]. This negative relationship was thought to be influenced by metabolic and neurophysiological causal factors other than alcohol, and by the physical health, social behaviors, and lifestyles of moderate drinkers. In an occupational cohort study of Japanese subjects, Fukunaga et al. found that moderate alcohol consumption or alcohol abstinence was associated with a reduced incidence of depression [9]. High amounts of alcohol consumption may cause neurophysiological and metabolic changes that increase the risk of depression. Thus, research on alcohol and depression has yielded mixed results and is an area that requires further research.
There are several populations that are prone to risky drinking. College students who have just started drinking demonstrate different drinking habits than older adults; specifically, many engage in binge drinking, that is, consuming a large amount of alcohol in a short period of time [10]. While numerous studies have investigated whether or not moderate or excessive drinking is associated with depression in adults [4, 11], few studies have examined the relationship between patterns of excessive drinking, such as binge drinking or heavy drinking, and depression in college students. When considering different drinking habits by age group, it is necessary to investigate if depression is related to temporary excessive drinking, which is common in college students, or to regular excessive drinking, or both. It is very important to clarify the relationship between depression and alcohol in Japan, because college students include many young people who are valuable labor resources given Japan's low birthrate and aging society, and should be a focus of health maintenance and promotion efforts. There have been limited studies regarding alcohol and depression in East Asian populations, including Japanese, and only a small number of studies have considered that alcohol metabolism differs by race. Alcohol is metabolized and converted to acetaldehyde by alcohol dehydrogenase, and acetaldehyde is then detoxified by aldehyde dehydrogenase 2 (ALDH2) [12, 13]. Compared with Caucasian people in Europe and North America, and with people belonging to African ethnic groups, East Asian people, including Japanese, frequently exhibit low or no ALDH2 activity [14]. This is likely to affect the impact of alcohol exposure on drinking‐related issues [15]. Continued alcohol consumption may be difficult among people with the inactive form of ALDH2, due to uncomfortable symptoms that appear after drinking (flushing, increased heart and respiratory rates, headache, and vomiting). For example, while alcohol use disorders have been shown to increase the risk of depression in European and North American populations [16], this relationship may be different in Asian populations with different metabolic enzymes.
Few studies have examined the direct relationship between alcohol and depression in Asian college students. One had a small sample size [17], and another defined the outcome as the incidence of problem drinking [18]. The present cross‐sectional study in Japanese college students was conducted to investigate the relationship between depression and two risky drinking patterns, specifically binge drinking and heavy drinking, in East Asian individuals (characterized by different alcohol metabolism than other populations) who were young and thus had shorter exposure to alcohol than older people. With this study, we test our hypothesis: Is there a significant relationship between depression and excessive alcohol consumption in the Asian population, and if so, is it a positive or negative relationship?
2. Materials and Methods
2.1. Study Design and Participants
In this cross‐sectional study, an anonymous, self‐administered questionnaire was completed by undergraduate and graduate students aged 20 years or older during annual health examinations at two universities in Ibaraki and Mie prefectures of Japan in April 2019 and January 2020. In Japan, drinking is prohibited by law for those under the age of 20, and therefore this study enrolled individuals aged 20 years and over. Some students under the age of 20 who mistakenly participated were excluded. Students who did not complete the questionnaire and those with missing data were also excluded. The prevalence of depression among nondrinkers has been shown to differ between two subgroups: people who have always been teetotalers and those who are ex‐drinkers [19]. Nondrinkers include lifetime nondrinkers and abstainers, and both groups are known to have poorer health and activity than drinkers [6]. Nondrinkers were excluded from this study because their characteristics may have biased the results.
2.2. Data Collection
The questionnaire addressed the following: (1) the amount of alcohol consumed on a typical day in which the participant engaged in drinking as open ended formats, (2) the weekly frequency of alcohol consumption by selecting one of several answers that ranged from every day to less than once per year, (3) the frequency of binge drinking during the past month, as evaluated by the following question: “During the last 1 month, how often did you have five or more (males) or four or more (females) drinks containing any kind of alcohol within a 2‐hour period?” (Yes: one or more; or No), (4) present smoking (Yes or No), (5) culture club activities (Yes or No), (6) athletic club activities (Yes or No), (7) demographic data; gender (female or male) and age(open ended formats), (8) the Center for Epidemiologic Studies Depression Scale (CES‐D), (9) the Alcohol Use Disorders Identification Test (AUDIT), (10) the flushing questionnaire, and (11) the Brief Sensation Seeking Scale (BSSS). To accurately assess alcohol consumption, students were required to list the number and types of drinks they consumed. The types of alcohol in the questionnaire included sake, beer, shochu (Japanese distilled beverage), chuhai (spirit‐based cocktail), cocktails, plum wine, whiskey, and wine.
In Japan, one unit of alcohol is defined as 10 g. Thus, we defined “binge drinking” as 50 g (five drinks) or more for men and 40 g (four drinks) or more for women in a 2‐h period [11, 20]. The amount of weekly alcohol consumption was derived by multiplying the number of days per week that alcohol was consumed by the amount consumed per drinking session. We defined “heavy drinking” as a weekly pure alcohol intake of ≥ 140 g for men and ≥ 70 g for women. These thresholds were determined with reference to both a prior Japanese study on university students and international guidelines such as the Dietary Guidelines for Americans, 2020–2025, which advise limiting alcohol consumption to no more than two standard drinks per day for men and one for women [11, 21].
The CES‐D is a simple self‐rating scale for depression. The questionnaire consists of 20 items, each of which includes four statements rated on the following 4‐point scale: “Rarely or none of the time (less than 1 day),” “Some or a little of the time (1–2 days),” “Occasionally or a moderate amount of time (3–4 days),” and “Most or all of the time (5 days or more).” Participants were asked to select the response that most accurately described how they felt during the past week. The total score, from 0 to 60, indicates depression severity [22]. In the original version, the cutoff score for the diagnosis of depression was set at 16 points [23], and this cutoff was determined to be appropriate in a reliability and validity study conducted in Japan [24]. The questionnaire's sensitivity and specificity for identifying depression were 95.1% and 85.0%, respectively [25].
AUDIT is a 10‐item screening tool for alcohol use disorders developed by the World Health Organization to evaluate alcohol consumption, drinking behaviors, and alcohol‐related problems [26]. The questionnaire consists of 10 items with a total score from 0 to 40.
The flushing questionnaire was developed by Yokoyama and colleagues to determine whether ALDH2 is active or inactive [27]. It consists of two questions: (1) Do you experience facial flushing immediately after drinking a glass of beer? and (2) Did you experience facial flushing immediately after drinking a glass of beer during the first to second year after you started drinking? The questionnaire's sensitivity and specificity for identifying inactive ALDH2 were shown to be 90.1% and 88.0%, respectively.
The BSSS is an eight‐item screening tool for sensation seeking developed by Hoyle [28], and it was translated into Japanese by Shibata et al. [29]. Sensation seeking is a psychobiological personality characteristic that describes the pursuit of experiences that are novel, complex, and intense, and the willingness to accept risky behavior [30].
2.3. Statistical Analyses
The Centers for Disease Control and Prevention (CDC) defines excessive drinking as encompassing both binge drinking and heavy drinking [31]. Guided by this definition, we focused on how these two patterns may occur independently or in combination. To ensure mutually exclusive categories and avoid variable overlaps, excessive drinking was classified into three groups: (i) binge drinking only, (ii) heavy drinking only, and (iii) both binge and heavy drinking. The t‐test was used to compare age, alcohol consumed per day, and AUDIT and BSSS scores. The Mann–Whitney U test was used to compare drinking frequencies between individuals with excessive versus non‐excessive drinking. The chi‐squared test was used to evaluate the relationship between excessive alcohol use and depression, gender, flushing, extracurricular activities, and smoking.
In a multiple logistic analysis using the forced‐entry method, “excessive drinking,” “heavy drinking,” “binge drinking,” and “binge drinking and heavy drinking” were used as objective variables, and depression was used as the explanatory variable. Age, gender, flushing response, AUDIT score, BSSS score, involvement in culture‐oriented clubs, participation in athletic clubs, and smoking were selected as covariates because each has been empirically linked to alcohol use patterns. Specifically, age and gender reliably predict quantity and frequency of drinking [32]; the alcohol‐flush reaction modulates consumption among East Asians [14, 33]; higher AUDIT scores reflect greater hazardous use [26]; elevated BSSS scores denote sensation‐seeking traits that foster heavier drinking [28]; membership in culture clubs or athletic teams shapes peer norms and heavy‐episodic drinking [34, 35, 36, 37]; and smoking co‐occurs with heavy drinking and alcohol use disorders [38]. If there was multicollinearity between variables using the variance inflation factor, then one variable was removed. p < 0.05 was considered statistically significant. The Bonferroni correction was applied to adjust for multiple comparisons. All statistical analyses were performed using Stata 13.1 for Macintosh (Stata Corp., College Station, TX, USA).
2.4. Ethical Considerations
To obtain participant consent, we distributed questionnaires and explained their content and purpose in writing and verbally. This research was approved by the medical ethics committee of University of Tsukuba (No. 1376) and Mie University (No. 1314).
3. Results
During annual health examinations, the questionnaire was distributed to 6447 students at Mie University and Tsukuba University, and 5629 students (87.3%) responded. Respondents were excluded if they had no history of drinking (214 students) or had missing data (880 students), and the data of the remaining 4535 students (80.6%) were analyzed. A flow chart is shown in Figure 1.
FIGURE 1.
Study flow chart.
Table 1 shows the participant characteristics. The prevalence rate of depression was 32.5%. Excessive drinking was reported by 35.8% of all participants, of whom 66.3% were male and 33.7% were female. Among excessive drinkers, the amount of alcohol consumed was 53.5 ± 33.2 g/day, and the frequency of drinking was 1.72 ± 1.62 days/week. Among all participants, the AUDIT score was 4.8 ± 3.9, the BSSS score was 19.6 ± 5.9, and 35.6% experienced flushing. Gender, alcohol consumed (g/day), frequency of drinking (days/week), AUDIT and BSSS scores, and smoking differed significantly between groups with or without excessive drinking.
TABLE 1.
Participants' characteristics and comparisons by drinking behavior.
| Variable | Total | Excessive drinking e | Non‐excessive drinking e | p |
|---|---|---|---|---|
| N = 4535 | n = 1624 (35.8%) | n = 2911 (64.2%) | ||
| Age (years), mean ± SD | 22.4 ± 3.3 | 22.3 ± 3.4 | 22.4 ± 3.3 | 0.27 b |
| Gender, n (%) | ||||
| Men | 2775 (61.2) | 1076 (66.3) | 1699 (58.4) | < 0.001 a |
| Women | 1760 (38.8) | 548 (33.7) | 1212 (41.6) | |
| Depressive state, n (%) | ||||
| Yes (CES‐D ≥ 16) | 1474 (32.5) | 528 (32.5) | 946 (32.5) | 0.092 a |
| No (CES‐D < 16) | 3061 (67.5) | 1096 (67.5) | 1965 (67.5) | |
| Alcohol consumed (g/day), mean ± SD | 36.2 ± 27.6 | 53.5 ± 33.2 | 26.7 ± 17.7 | < 0.001 b |
|
Frequency of drinking (days/week), mean ± SD |
1.01 ± 1.27 | 1.72 ± 1.62 | 0.62 ± 0.78 | < 0.001 c |
| Flushing, n (%) | ||||
| Yes | 1612 (35.6) | 373 (23.0) | 1239 (42.6) | < 0.001 a |
| No | 2923 (64.4) | 1251 (77.0) | 1672 (54.4) | |
| AUDIT (points), mean ± SD | 4.8 ± 3.9 | 7.7 ± 4.2 | 3.1 ± 2.5 | < 0.001 b |
| BSSS d , mean ± SD | 19.6 ± 5.9 | 21.3 ± 6.0 | 18.7 ± 5.7 | < 0.001 b |
| Extracurricular activities, n (%) | ||||
| Culture club | 944 (20.8) | 327 (20.1) | 617 (21.2) | < 0.001 a |
| Athletic club | 1318 (29.1) | 592 (36.5) | 729 (24.9) | |
| Culture club + Athletic club | 169 (3.7) | 77 (4.7) | 92 (3.2) | |
| None | 2104 (46.4) | 628 (38.7) | 1476 (50.7) | |
| Smoking, n (%) | ||||
| Yes | 232 (5.1) | 156 (9.6) | 76 (2.6) | < 0.001 a |
| No | 4303 (94.9) | 1468 (90.4) | 2835 (97.4) | |
Chi‐squared test.
t‐test.
Mann–Whitney U test.
Brief Sensation‐Seeking Scale.
Excessive drinking is defined as binge drinking, heavy drinking, or both.
Table 2 shows the results of multiple logistic regression analysis. Excessive drinking was categorized as binge drinking (n = 1208, 74.4%), heavy drinking (n = 87, 5.4%) and the combination of binge drinking and heavy drinking (n = 329, 20.3%). Depression was found to be negatively associated with heavy drinking (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.36–0.98), but this did not reach the Bonferroni‐adjusted significance threshold. Excessive drinking was significantly related to male sex (OR, 1.24; 95% CI, 1.06–1.47), AUDIT score (OR, 1.55; 95% CI, 1.51–1.60), BSSS score (OR, 1.02; 95% CI, 1.01–1.04), athletic club activities (OR, 1.37; 95% CI, 1.13–1.65), and smoking (OR, 1.76; 95% CI, 1.24–2.51). The logistic regression model for excessive drinking showed a good overall fit (Likelihood ratio χ 2 = 1788.686, df = 10, p < 0.001). The area under the ROC curve (AUC) was 0.8642, indicating high discriminative ability. For the other models (binge drinking, heavy drinking, and binge drinking + heavy drinking), the likelihood ratio χ 2 statistics were also significant (p < 0.001), with degrees of freedom consistently equal to 10. The AUCs ranged from 0.7467 to 0.9052, suggesting acceptable to excellent model performance. The variance inflation factor was 1.13, which was ≤ 10, indicating the absence of multicollinearity.
TABLE 2.
Factors independently related to excessive drinking (N = 4535).
| Binge drinking a | Heavy drinking b | Binge drinking + Heavy drinking | Excessive drinking c | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n = 1208 (26.6%) | n = 87 (1.9%) | n = 329 (7.3%) | n = 1624 (35.8%) | |||||||||
| Odds ratio | 95% CI | p | Odds ratio | 95% CI | p | Odds ratio | 95% CI | p | Odds ratio | 95% CI | p | |
| Depressive state | ||||||||||||
| Yes (CES‐D ≥ 16) | 0.89 | 0.76–1.03 | 0.128 | 0.59 | 0.36–0.98 | 0.041 | 1.10 | 0.83–1.46 | 0.492 | 0.87 | 0.73–1.02 | 0.088 |
| No (CES‐D < 16) | Reference | Reference | Reference | Reference | ||||||||
| Age | 0.97 | 0.94–0.99 | 0.009 | 1.02 | 0.97–1.07 | 0.433 | 1.06 | 1.02–1.10 | 0.003 | 1.00 | 0.97–1.03 | 0.994 |
| Gender | ||||||||||||
| Men | 0.84 | 0.72–0.98 | 0.025 | 1.52 | 0.97–2.40 | 0.071 | 2.28 | 1.70–3.05 | < 0.001 | 1.24 | 1.06–1.47 | 0.007 |
| Women | Reference | Reference | Reference | Reference | ||||||||
| Flushing | ||||||||||||
| Yes | 0.65 | 0.55–0.76 | < 0.001 | 0.68 | 0.40–1.16 | 0.158 | 0.52 | 0.37–0.74 | < 0.001 | 0.67 | 0.56–0.79 | < 0.001 |
| No | Reference | Reference | Reference | Reference | ||||||||
| AUDIT | 1.16 | 1.13–1.18 | < 0.001 | 1.15 | 1.11–1.20 | < 0.001 | 1.39 | 1.34–1.43 | < 0.001 | 1.55 | 1.51–1.60 | < 0.001 |
| BSSS d | 1.03 | 1.01–1.04 | < 0.001 | 1.01 | 0.97–1.05 | 0.675 | 1.01 | 0.99–1.04 | 0.323 | 1.02 | 1.01–1.04 | 0.001 |
| Extracurricular activities | ||||||||||||
| Culture club | 1.08 | 0.89–1.32 | 0.412 | 1.16 | 0.66–2.05 | 0.601 | 1.17 | 0.81–1.70 | 0.389 | 1.16 | 0.94–1.43 | 0.156 |
| Athletic club | 1.46 | 1.23–1.73 | < 0.001 | 0.78 | 0.45–1.36 | 0.375 | 1.03 | 0.74–1.43 | 0.881 | 1.37 | 1.13–1.65 | 0.001 |
| Culture club + athletic club | 1.22 | 0.85–1.76 | 0.280 | 1.23 | 0.45–3.34 | 0.688 | 1.71 | 0.92–3.17 | 0.091 | 1.43 | 0.96–2.12 | 0.077 |
| None | Reference | Reference | Reference | Reference | ||||||||
| Smoking | ||||||||||||
| Yes | 0.81 | 0.60–1.11 | 0.191 | 1.41 | 0.66–2.98 | 0.375 | 3.78 | 2.55–5.60 | < 0.001 | 1.76 | 1.24–2.51 | 0.002 |
| No | Reference | Reference | Reference | Reference | ||||||||
Note: Multivariate logistic regression. A Bonferroni‐adjusted significance threshold of p = 0.0125 (0.05/4) was applied.
Abbreviations: 95% CI, 95% confidence interval; p, p value.
Binge drinking is defined by the number of drinks consumed per occasion: five or more for men, and four or more for women.
Heavy drinking is defined as weekly pure alcohol intake of over 140 g for men and over 70 g for women.
Excessive drinking is defined as binge drinking, heavy drinking, or both.
Brief Sensation‐Seeking Scale.
4. Discussion
This large study of Asian college students showed a negative association between depression and heavy drinking (OR, 0.59; 95% CI, 0.36–0.98). This result, as well as a prior study [4], suggest that the negative relationship between depression and drinking indicates that individuals with depression may be unlikely to engage in heavy drinking, rather than that drinking ameliorates one's depression.
One potential reason for our findings is that people are more likely to increase their alcohol consumption when they feel positive. People with mood disorders such as depression often drink alcohol as a form of self‐medication [39, 40], because drinking is generally thought to temporarily elevate mood. However, Tovmasyan et al. conducted a systematic review and meta‐analysis of mood changes and alcohol consumption and reported that alcohol consumption increased when daily emotional states were positive but not negative [41]. Depression is associated with an inability to enjoy things that were once enjoyable [42], which may explain the negative relationship between depression and heavy alcohol consumption.
In this study, depressive symptoms tended to be inversely associated with habitual heavy drinking, whereas they tended not to be associated with either binge drinking or the combined pattern of binge and heavy drinking. This finding aligns with evidence indicating that episodic, high‐intensity drinking among university students is governed chiefly by peer norms and other social‐contextual forces rather than by individual affective states. Borsari and Carey's seminal review identified peer influence as the most robust predictor of collegiate binge drinking, whereas mood‐related variables showed only modest and inconsistent effects [43]. A latent‐growth analysis of 404 Asian American students further showed that baseline depression scores did not differentiate trajectory classes of heavy‐episodic drinking [44].
There are four main limitations to this study. The first is geographical bias, since the survey was performed at two national colleges in Japan. Approximately 600 000 students were attending public national colleges and universities in Japan in 2022. Furthermore, approximately 160 000 students were attending other public colleges and universities, and 2 170 000 were attending private colleges and universities [20, 45]. Therefore, there are limitations to generalizing the results of this study to the entire population of Japanese college students. A second limitation is the possible presence of recall bias. Because participants in this study used a self‐administered questionnaire to report past histories of alcohol consumption, the actual amount of alcohol consumed may have differed from that reported. However, depression was evaluated by the CES‐D scale, and about 30% of the study participants were assessed as having depression, which is consistent with the nationwide prevalence rate in Japan. Third, nondrinkers were excluded. As mentioned above, 214 nondrinkers were excluded due to the possibility of including students with poor health. Although this number was not very large, the exclusion may have influenced the results. Finally, we cannot determine the causal relationship between excessive alcohol use and alcohol‐related injuries due to the cross‐sectional nature of this study. This limitation warrants further investigation to clarify causation.
This survey of Japanese college students revealed that depression was significantly inversely associated with heavy drinking. More detailed research is required on the relationship between alcohol and depression by age group and race.
Author Contributions
G.S. and H.Y. designed the study; G.S. collected data; G.S. and H.Y. analyzed data and wrote the manuscript. All authors contributed to the intellectual content of this manuscript and approved the final manuscript as submitted.
Ethics Statement
To obtain participant consent, we distributed questionnaires and explained their content and purpose in writing and verbally. Approval of the research protocol by an Institutional Reviewer Board: This research was approved by the medical ethics committee of University of Tsukuba (No. 1376) and Mie University (No. 1314).
Consent
Written informed consent was obtained from all participants prior to their inclusion in the study.
Conflicts of Interest
Hisashi Yoshimoto received research funding from Asahi Breweries and Sanwa Shurui; this funding was not related to the conduct of the study.
Acknowledgments
We thank the health examination staffs of Mie University and Tsukuba University for their help with the data collection.
Saito G., Yoshimoto H., Takayashiki A., Kawaida K., Shiratori Y., and Maeno T., “The Association Between Excessive Drinking Patterns and Depression: A Cross‐Sectional Study in College Students in Japan,” Neuropsychopharmacology Reports 45, no. 3 (2025): e70048, 10.1002/npr2.70048.
Funding: The authors received no specific funding for this work.
Data Availability Statement
The data generated in this study are derived from a survey conducted among college and graduate students. As these participants constitute a socially vulnerable population in research, making the data publicly available without obtaining explicit consent from them would raise significant ethical concerns. For this reason, the datasets supporting the conclusions of this article are not publicly accessible; however, the data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data generated in this study are derived from a survey conducted among college and graduate students. As these participants constitute a socially vulnerable population in research, making the data publicly available without obtaining explicit consent from them would raise significant ethical concerns. For this reason, the datasets supporting the conclusions of this article are not publicly accessible; however, the data that support the findings of this study are available from the corresponding author upon reasonable request.