Does Circadian Preference Determine Risk for Developing Alcohol Use Disorder amongst Undergraduate and Pre-University Students? A Cross-Sectional Study

Aims: To determine the relationship between circadian preference and risk for developing alcohol use disorder among medical students and pre-university students. Study Design: An analytical cross sectional study was conducted among non-Muslim Place and Duration of Study: Melaka, Malaysia from September to October 2014. Methodology: 250 participants were selected by using multistage sampling method, 223 students participated (89.2% resposnse rate). Sociodemographical data, assessment of circadian preference by International Journal Chronobiology (IJC) and WHO Alcohol Use Disorder Identification Test were collected using a structured questionnaire. Bivariate analysis, chi-square test, Fisher Exact test and multiple logistic regression analysis were calculated. Results: Out of 223 non-Muslim undergraduate students, 60.09% were having intermediate type, 21.97% were having evening type and 17.94% were having morning type of circadian preference. Only 17.04% of the participants were having moderate, high and addictive alcohol consumption risk; among them 7.9% were addictive and 10.5% were high risk. Participants with evening type of circadian preference were 4.5 times more likely to be associated with a higher risk for developing alcohol use disorder as compared to participants with morning type of circadian preference (OR 4.5, 95% CI 1.2-17.0, P=0.02). After adjusted for age, gender, ethnicity, hostel and monthly allowance, evening type of circadian preference and risk for developing alcohol use disorder were not significantly associated to each other. Conclusion: Circadian preference was significantly associated to the risk for developing alcohol use disorder among the undergraduate and pre-university students in bi-variate analysis without considering other factors such as age, gender, ethnicity and monthly allowance. However, no significant association were found among each of the factors that were being compared. This was because there was a confounding variable which was gender affecting the result. In our study, male students had a higher risk in developing AUD and male students were more likely to have evening type of cicadian preference. We should provide adequate counseling about sleep hygiene, healthy sleep-wake cycle and encourage students to develop morning type of circadian preference in order to reduce the risk of developing alcohol use disorder. risk for developing alcohol use disorder; medical students; pre-university students; cross sectional study.


INTRODUCTION
Circadian preference is referred to the morningness, intermediate and eveningness of an individual who has different alertness, activities and sleep wake cycle in the morning and evening. A morning type person wakes up early, is able to perform physical activities more easily in the morning, is more mentally alert early in the day and goes to bed early in the evening. Individuals who described as an evening type person wakes up late in the morning, sleep late at night, having physical activities and mental alertness best performed in the evening [1].
According to WHO global status report on alcohol and health 2014, harmful use of alcohol caused 3.3 million deaths in 2012, caused injury and illness to millions more, and increasingly affected the younger generation in developing countries. 5.9% of all global deaths were related to alcohol [2]. In other country such as US, a cohort study showed that 78% of US medical student having alcohol in previous month and 44% of them drink excessively [3]. 89% out of 3075 UK university second year students were drinkers. Among the drinkers 15% of them were hazardous drinkers and 28% of them were binge alcohol consumers [4]. A study also shows that 45% of the UK first year medical students exceeded the recommended UK limits for alcohol consumption [5].
In Malaysia, according to World Health Organization Report in year 2014 (Global Status Report on Alcohol and Health: Individual Country Profile, Malaysia), 12.7% of Malaysian consumed alcohol [6]. Prevalence of heavy episode alcohol consumption in Malaysia in year 2010 was 2.5% and prevalence of alcohol use disorder (AUD) among both sexes in Malaysia in year 2010 was 2.4% [6].
In a study done in 2011, individual with morning type of circadian preference was significantly associated with lower chance of having healthimpairing behaviours such as daily smoking (p < .0001) and alcohol use (p < .0001). Therefore, the circadian preference of eveningness type was associated more with health impairing behaviour like smoking and alcohol use compared to morningness and intermediate group [1]. A few studies had been done and they stated that the personality and psychosocial activities of an individual such as alcohol use were associated with the individual's circadian preference [7,8]. Moreover, a study on circadian gene polymorphism in alcohol use disorder and alcohol consumption reported that there was an association between ARNTL (a transcriptional complex), ADCYAP1 (a neurotransmitter of the retinohypothalamic tract) and VIP (participates in maintaining oscillations within and sending signals from the SCN) with alcohol consumption, DRD2 with alcohol sensitivity and ARNTL2 with alcohol abuse [9].
To the best of our knowledge, no similar research was conducted to study the relationship between circadian preference and risk for developing alcohol use disorder in Malaysia. Thus, this study was carried out to know how circadian preferences affect the risk for developing alcohol use disorder among undergraduate medical students and preuniversity students.

MATERIALS AND METHODS
This analytical cross sectional study was conducted to find out the association between circadian preference and risk for developing alcohol use disorder among undergraduate medical students of a private medical college in Melaka, Malaysia from September 2014 to October 2014.
Our sample size was calculated using formula to estimate single population proportion with prevalence of 12.7% Malaysian who consumed alcohol according to WHO's global status report in Malaysia 2014 [6]. 95% confidence interval, 5% precision and minimum number of 171 students was required.  [10]. We were able to categorize the participants into morningness, intermediate and eveningness based on a total number of 19 structured questions. The questions were regarding time they usually go to bed, time preference to perform physical activities, time they would get up if they were entirely free the whole day and alertness after a sleep. Circadian preference was categorized based on total scores obtained from the 19 questions into morningness, intermediate and eveningness by following the marking scheme suggested by J.A. Horne and O.Osterg, International Journal Chronobiology (IJC) [10]. Scores can be ranged from 16-86. Scores of 41 and below were catogerized into eveningness, scores of 59 and above were categorized into morningness and scores between 42-58 were intermediate [10]. The scores for low risk alcohol consumers will be in the range from 0 to 7 in the questionnaire [11]. Low risk alcohol consumers indicates that the participants are having low risk for developing an alcohol use disorder (AUD) as defined by NIAAA and only require alcohol education as recommended by WHO [11,12]. NIAAA research showed that only about 2% people of this category had an AUD [12]. Participants who were categorized in low risk AUD need minimal intervention whereas for those who have scores of more than 7 were considered as moderate risk to addictive alcohol consumers who need more intervention [11].

Statistical Analysis
The data from questionnaires were tabulated in Microsoft Excel. We analyzed data using Epi Info 7 and SPSS software for both descriptive and inferential statistics. For descriptive statistics frequency, percentage, mean and standard deviation were used. For bivariate analysis, chisquare test and Fisher Exact test were used and multiple logistic regression analysis were used aw well to find the association of circadian preference and other demographic factors with risk for developing AUD. Significance level was set at 0.05. Odds ratio and its 95% confidence interval were described.
After getting approval from Research Committee of Melaka Manipal Medical College, students were approached during class period. Students were briefly explained regarding our research topic and consent from participants were taken in verbal and written form. Confidentiality of the data collected was ensured.

Socio-demographic Characteristic of Students
In Table 1, 223 of non-Muslim students responded to this study. 18.4% of the students were categorized in age group below 21, 52.5% of the students were 21 to 23 years old and 29.1% of them were 24 years old and above. 55.2% of the participants were male and 44.8% were female. There were 60.1% of Chinese and 39.9% of Indian participants. There were 13% of students who were having a monthly alowance of RM500 and below. 56.5% of them were having monthly allowance of RM501-800 and 28.7% of the students were having RM801 and above per month.

Prevalence of Circadian Preference in Study Participants with Different Characteristic
Out of 223 participants, 60.09% of them were having intermediate type of circadian preference, 21.97% of them were evening type and 17.94% of them were having morning type of circadian preference as shown in Table 2. Male students who were categorized in evening type of circadian preference were having a higher percentage which was 27.6% as compare to eveing-type female students who were only 15%.

Risk for Developing Alcohol Use Disorder among Students
In Table 3, 82.96% of the participants were categorized as low risk alcohol consumers, 13.90% of them were moderate risk alcohol consumers, 1.79% of them were categorized as high risk and 1.35% of them were addicted to alcohol.

Association between Circadian Preference and Risk for Developing Alcohol Use Disorder
In Fig. 1, highest percentage of medical students with evening type of circadian preference were moderate risk to addictive alcohol consumers as compared to other circadian preferences. On the other hand, higher percentage of medical students with morning type of circadian preference were low risk alcohol consumer.

Bivariate Analysis and Multiple
Logistic Regression Analysis of Association between Circadian Preference and Risk for Developing Alcohol Use Disorder 17.04% of the participants were at moderate risk, high risk and addictive alcohol consumers and 82.96% of them were having low risk for developing alcohol use disorder. Participants with evening type of circadian preference were 4.5 times more likely to associate with higher risk for developing alcohol use disorder as compared to participants with morning type of circadian preference in bi-variate analysis(Unadjusted OR 4.5, 95% CI 1.2-17.0, P=0.02) but after they were adjusted for age, gender, ethnicity, hostel and monthly allowance in multiple logistic regression analysis, they were not significantly associated to each other.

Bivariate Analysis and Multiple
Logistic Regression Analysis of Relationship between Sociodemographic Characteristics and Risk for Developing AUD Compared to females, males were 4.5 times more likely to develop AUD (OR 4.5, 95% confidence interval [CI] 1.9 -10.7). Students with monthly allowance more than RM 800 were 2.5 times more likely to be associated with a higher risk for developing AUD than students having monthly allowance from RM 501 to RM 801. Other than that, there were no significant association between age, ethnicity or accommodation with risk for developing AUD.

DISCUSSION
An analytical cross sectional study was conducted to find out the association between circadian preference and risk for developing alcohol use disorder among 223 non-Muslim medical students and pre-university students of a private medical college in Melaka, Malaysia. Out of 223 students, 60.09% were intermediate type, 21.97% were evening type and 17.04% were morning type of circadian preference. 82.96% of the participants were found to be low risk alcohol consumers, 13.90% of them were moderate risk, 1.79% of them were high risk and the remaining 1.35% of them were addicted to alcohol. "Chronotype and personality factors in the daily consumption of alcohol and psycho also found that evening-type person was significantly more likely to be associated with alcohol consumption as compared to morning type person [7]. Individual with morning type of circadian preference was reported to be significantly associated with a lower chance of having health-impairing behaviours such as daily Individual with morning type of circadian preference was reported to be significantly associated with a lower chance of impairing behaviours such as daily   smoking (p < .0001) and alcohol use (p < .0001) in a study done in 2011 [1]. Furthermore, a study done on circadian gene polymorphism supported that there was association between circadian genes with alcohol consumption and alcohol abuse [9]. Hence, circadian preference of a person should be considered as an additional factor in alcohol consumption [13]. However, after taking consideration on other factors such as age, gender, ethnicity and monthly allowance in our study, the adjusted OR showed 3.6 with 95% confidence interval of 0.9-15.0 which was not significant. This was because the number of male among the participants from evening type of circadian preference was more than the number of male participants from morning type. Apart from that, female had higher number of morningness as compared to eveningness. In our study, the gender was also significantly associated with risk for developing alcohol use disorder. Male students were more likely to have evening type of circadian preference. Therefore, gender was a confounding variable that has affected the result to become not significant.

Moderate Risk to Addictive Alcohol Consumption
As mentioned above, we found that the gender was significantly associated with higher risk for developing alcohol use disorder. In our study, male students were 4.5 times more likely to consume alcohol (Unadjusted OR 4.5, 95% CI 1.9-10.7). A study by WHO, global status report on alcohol and health (country profile: Malaysia) found that gender was a factor associated with alcohol consumption among non-Muslim adults [6]. Likewise as from a research done to study tobacco and alcohol use among medical students in 1996, there was an association between gender and alcohol consumption [14]. The most probable reason for drinking was pleasure, followed by habit, to increase confidence, release anxiety or stress and social pleasure [4].
Furthermore, students with monthly allowance ≥RM 801 were 2.5 times more likely to be associated with a higher risk for developing alcohol use disorder than students having monthly allowance between RM 501-800 (Unadjusted OR 2.5, 95% CI 1. 1-5.4). This showed that students with a higher socioeconomic status were more able to afford the expenses on alcohol drinks. It was corresponding to other researches that had been done. They said that, individual with higher monthly allowance have higher tendency to consume alcoholic drinks [15,16].

STRENGTH
Participants who had done the survey were given reassurance that data will be kept anonymous by removing participants name. Privacy and Confidentiality were ensured.

LIMITATION
There were a few limitations which may affect the outcome of our study. Firstly, a small number of the selected students who consume alcohol refused to respond to the questionnaires and may affect the results of our study. Secondly, due to religious belief, our questionnaires were distributed only to nonmuslim students. Thirdly, there could be underreporting of other health risk behaviours in this study like smoking and drug use. This study had not explored the association of circadian preference with the other health risk behaviours such as drunk driving, elicit drug use, suicide, promiscuity, etc. Our study statistics were not representative for any other age group and not representing the whole Malaysian population as we conducted this study in a private college in Melaka only.

RECOMMENDATION
Our study suggests an obvious need for an effective educational and prevention programs targeted toward improving sleep hygiene and reducing alcohol consumption among young adults. From our point of view, students are encouraged to develop morning type of circadian preference. Other studies had shown that evening type of circadian preference might contribute to antisocial behaviours and substance abuse that may have serious implication in later life. Besides that, we should provide adequate counseling to medical students about the disadvantages of alcohol use. A referral to specialist for diagnosis, evaluation and treatment should be done for those who were in addictive category as recommended by WHO [11] Based on our study, senior batches were more likely to consume alcohol compared to foundation students as this might be due to workload that they encountered. By educating them on time and stress management, the amount of students consuming alcohol would significantly decrease. In addition, institution should organize more extra-curricular activities after class period and motivate student to be more physically active. In turn, it is able to prevent students from consuming alcohol during their free time and it provides opportunities for the students to relieve stress.

CONCLUSION
According to WHO alcohol identification test in our study, 13.9% of the participants were having moderate risk for developing alcohol use disorder, 1.79% were high risk and 1.35% were addictive to alcohol. As a conclusion, circadian preference of a person should be considered as an additional factor in alcohol consumption especially in the context of risk for developing AUD. Although circadian preference was only signifcantly associated to the risk for developing alcohol use disorder in bi-variate analysis before adjusted with other factors in multiple logistic regression, the relationship between circadian preference and risk for developing alcohol use disorder among the alcohol consumers should not be neglected. We should provide adequate counseling about sleep hygiene, healthy sleepwake cycle and encourage students to develop morning type of circadian preference in order to reduce the risk of developing alcohol use disorder. Students are discouraged from developing evening type of circadian preference as it may contribute to negative psychosocial behaviours and substance abuse especially alcohol consumption which may have serious implication in later life.

ETHICAL APPROVAL
All authors hereby declare that the conduct of this research was approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Consents from participants were taken in verbal and written form. Confidentiality of the data collected was ensured.