Alcohol dependence is a maladaptive pattern of excessive drinking that leads to serious problems. Many evidences suggest that it is a complex genetic disease, with variations in large number of genes that affect the risk. The age of onset of alcohol use and a family history of alcohol dependence, both can influence a person’s risk of becoming alcohol dependent. Lee and DiClemente defined age of onset as “the age at which a consistent pattern of heavy alcohol use was established” [1]. The course of Alcohol Use Disorders is as predictable as most medical and psychiatric conditions, with an early onset likely to be associated with greater severity. A person's likelihood of developing alcohol dependence can be influenced by their age when they start alcohol consumption as well as family history of alcohol dependence. The 1992 National Longitudinal Alcohol Epidemiologic Survey data was used to examine the association between age at first alcohol use, lifetime alcohol dependency, and a family history of alcohol dependence. This analysis showed that respondents with an earlier age of drinking onset were more likely to become alcohol dependent compared to respondents with a later age of drinking onset, despite the family history of alcohol dependence [2]. The peak ages of onset usually are from the early 20s to about age 40. Onset after age of 40 tends to be associated with less severe social difficulties and more subtle signs and symptoms, but greater likelihood of medical problems. According to epidemiologic estimates, the likelihood of developing an alcohol dependence is almost four times higher for individuals who started drinking at age 14 or less than for those who started drinking at age 20 or older [3]. Likewise, a plethora of research has indicated that individuals with first-degree relatives who are alcoholics have a two to seven times higher likelihood of experiencing alcohol-related issues later in life compared to those who had non-alcoholic ancestors [4]. Research indicates that an early introduction to alcohol is linked to aggressiveness, legal issues, [5] maladaptation to social roles, loss of self-control when drinking, and juvenile delinquency [6,7]. Several reasons for beginning alcohol consumption at a young age have been presented, including peer pressure, curiosity, and experimenting. They also tended to be more sensation seekers and showed signs of hostility, violence, and general lack of restraint when they were under the influence [8]. According to an Indian study, the age at which alcohol usage began was 18 years, and the age at which dependence began was 27 years. Additionally, they discovered that after six years of alcohol consumption, these individuals met the initial criteria for dependence and another few years to meet the criteria for dependence syndrome [9]. In Indian culture, it is unknown how the severity of alcohol dependence is related to family history and the age at which it first appears. The purpose of this study is to examine if there is a relationship between these variables and the level of alcohol dependence.

We recruited male patients between age group of 18 to 60, admitted consecutively for alcohol-related problems, to medical, surgical, orthopaedic, and psychiatric wards in a large teaching general hospital, over a period of 12 months. This is a tertiary care hospital, catering to the rural and urban population of Maharashtra. The study was approved by the institutional ethics review board. Sample size was calculated by using statistical formula- n = Z2 P(1-P)/d2 Where, P = Population Proportion [of alcohol dependence syndrome] - 12.8% [10] 1-α = Confidence interval [95%]; Z = Z value associated with confidence [1.96] D = Absolute precision (value less than P) [10.00%] N = minimum sample size = 43. However, 60 participants were included in the study. Subjects will be diagnosed with Alcohol dependence syndrome based on ICD-10 criteria for research.[11] Subjects will first be administered Alcohol Use Detection Inventory Test [AUDIT] [12], and those scoring more than 8 were administered the Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar] [13] to rule out persistent withdrawal symptoms. Subjects scoring less than 8 were included in the study. AUDIT has been validated and widely used in India [12]. Subjects who were clinically diagnosed cases of other primary psychiatric illnesses or end-stage medical illnesses were excluded. The subjects were then administered a semi-structured proforma and assessed for severity of alcohol dependence using the Severity of Alcohol Dependence Data [SADD] questionnaire. It is a 15-item questionnaire that has been developed to provide a brief and replicable method of assessing the severity of alcohol dependence [14]. Next, we assessed the age of onset of initiation, using the definition described by Lee and DiClemente as “the age at which a consistent pattern of heavy alcohol use was established." Subsequently, the age of onset was divided into two groups (early onset and late onset). Early onset consisted of subjects with the age of onset less than and equal to 25 years, and late onset consisted of subjects with the age of onset beyond 25 years. Later, the Family Interview for Genetic Studies (FIGS) alcohol section was used to evaluate the relatives for alcohol dependent syndrome [15]. While the data for FIGS was gathered from a reliable informant in this study. FIGS is an interview guide based on the Research Diagnostic Criteria. It aids in obtaining details about ancestors within the lineage under study. When the subject's information is unreliable, it is especially crucial. Positive family history was coded when any of the 3 generations were found to meet criteria for alcohol dependence and negative if none. We modified Family History Density [FHD] scoring used by Johnson PR et al.[20], to assess whether FHD has an association with alcohol dependence severity. Family History Density [FHD] was assessed by giving weighted points to family members with alcohol dependence based on their relatedness to the subject. Parents were given 2 points, and grandparents and uncles were given 1, whereas non-alcoholic relatives were given a score of zero. Scores were then summed from 2 generations to obtain a final FHD score. STATISTICAL ANALYSIS Statistical analysis was done using Microsoft Excel-365 and SPSS-29. Frequency and percentages were obtained for qualitative characters. The mean and SD were calculated for the SADD severity score and for FHD. The chi-square test was used to check the associations between categorical variables.

Sixty participants were included in this study and all of these were male alcoholics. The Sociodemographic variables such as current age, marital status, educational status, and occupational status were not significantly associated with the severity of alcohol dependence. Table 1: Frequency and percentage of subjects according to Age of onset and Family history. Age of onset Frequency Percent[%] <= 25 yrs 28 46.7 > 25 yrs 32 53.3 Total 60 100.0 Family History NO 21 35.0 YES 39 65.0 Total 60 100.0 The division of subjects according to the onset showed 53.3% having late onset al.cohol dependence and majority [65%] of the sample had positive family history of alcohol dependence as shown in Table 1. Table 2: Descriptive statistics of SADD severity scores and FHD of the subjects. SADD Severity score FHD N 60 60 Mean 21.02 1.88 Median 21 2 Std. Deviation 4.261 1.805 Minimum 13 0 Maximum 35 7 Mean severity score on SADD scale was 21.02 that indicates high dependence as majority of the sample showed high dependence. The mean FHD obtained was 1.88 with maximum FHD of 7 as shown in Table 2. Table 3: Association between severity of alcohol dependence and age of onset, family history. Age of onset Severity Total[n] Significance High[n] Medium[n] [P value] <= 25 22 6 28 0.012 > 25 15 17 32 Family History Severity Total[n] Significance High[n] Medium[n] [P value] NO 8 13 21 0.006 YES 29 10 39 In table 3, a positive correlation was found between severity of alcohol dependence and age of onset [p value-0.012], as those with earlier age of onset of alcohol dependence had higher severity scores on SADD scale. In addition, significant association was also found between severity of alcohol dependence and family history [p value- 0.006], as those who had positive family history of alcohol dependence also scored higher on the SADD scale. Table 4: Comparison of mean FHD according to Severity and Age of onset N Mean FHD Std. Deviation Std. Error Mean Significance Severity High 37 2.38 1.82 0.30 t = 2.982 p = 0.004 Medium 23 1.09 1.51 0.31 Age of onset <= 25 28 3 1.66 0.31 t = 5.388 p < 0.001 > 25 32 0.91 1.30 0.23 In addition to the considering the presence of family history, participants with higher levels of alcohol dependence and younger onset ages also had higher FHD, according to the FHD calculation. Table 4 indicates a substantial correlation between mean FHD scores and age of onset and family history.

The concept of the ‘age of onset’ has been gaining a lot of interest, while a perfect definition is still unclear. Most of the authors have a different conception about the ‘age of onset’ of alcohol dependence. Latcham determined the age of onset of the problem-drinking by subtracting the number of years the subject declared he had found his ‘drinking had been a problem’ from his current age [16]. Irwin et al. defined the age of onset as the “age at which subject first met the DSM3R criteria for alcohol abuse or dependence,” [7], and Grant et al. defined the age of onset as the “age at which they first started drinking, not counting small tastes or sips of alcohol” [2]. We have used the Lee and Diclemente defined age of onset as “the age at which a consistent pattern of heavy alcohol use was established” [6]. Though definitions vary, there seems to be a persistent trend toward greater severity of alcohol dependence in people with younger onset ages. Consistent with earlier research, there is an inverse link between the age at which alcohol dependence first manifests and its severity [3] [17,18]. Varma et al.'s research, out of those conducted in India, does provide credence to the theory that the severity of alcohol dependence and its early onset age are related [8]. This study found that family history was more strongly associated with severity of alcohol dependence than age of onset, despite what was found in other studies such as those done by Grant [19], Johnson PR [20], and Hingson [21]. It was also discovered that the youngest age group had a substantial association with the influence of age of onset on the severity of alcohol dependence. In their research, Beth A. Reboussin found a substantial correlation between young adulthood drinking and regular problem drinking [22]. They also proposed that heavy drinking practices that may manifest in late adolescence were the most prominent feature of underage problem drinking. According to recent genetics research, 40-56% of the variation in adults' frequency and alcohol consumption is attributed to hereditary variables; furthermore, it is indicated that this genetic influence is constant throughout adulthood [23-25]. A variety of shared environmental measures are said to mediate further risk [26]. Another study done using similar methodology by Johnson PR et al. [20] also had similar findings, but in our study, not merely the presence or absence of family history but the mean FHD scores were also correlated with age of onset and severity of alcohol dependence. An inverse relationship between age of onset of alcohol dependence and FHD scores and a direct relationship between severity of alcohol dependence and FHD scores was seen. This was also seen in previous studies that used family history to study alcohol dependence. Hill and colleagues [27-29] found that high-risk children with a greater familial density of alcohol dependence have a higher risk for early alcohol initiation than those with a lower familial density of alcohol dependence. Family history density is an advancement in the methodology of family history as we have taken parents, grandparents, and uncles, which can be seen as a measure of genetic as well as biopsychosocial risk. The results take on great significance when one considers that the more "joint" Indian families are probably to have more shared environmental influences. This justifies a more thorough examination of family history and community influences within the Indian context. Previous research was conducted in alcoholic clinics and de-addiction centers, where the severity scores could be skewed; this study was conducted in a general hospital setting, where a wide range of severity can be expected. Another major strength of this study is the use of a reliable method of assessment of family history, which was taken from a reliable informant aside from the subject. Such studies, if done with a much larger sample size would yield more promising results which is the limitation of this study.

Using general hospital samples, we have shown that family history is more strongly associated with severity than age of onset. It was also seen that there is an inverse relationship between age of onset of alcohol dependence and FHD scores and a direct relationship between severity of alcohol dependence and FHD scores. The findings of our study point towards the importance of consideration of age of onset of alcohol dependence and the density of positive family history of alcohol dependence while dealing with patients of alcohol dependence. This provides a better understanding of the influence of genetic and environmental factors on alcohol dependence in Indian males, although a more extensive study on a wider range of Indian population is warranted.

1. Lee GP, DiClimente CC: Age of onset versus duration of problem drinking on the Alcohol Use Inventory. J Stud Alcohol. 1985, 46:398-402. 10.15288/jsa.1985.46.398 2. Grant BF: The impact of a family history of alcoholism on the relationship between age at onset of alcohol use and DSM-IV alcohol dependence: results from the national longitudinal alcohol epidemiologic survey. Alcohol health and research world. 1998, 22:144. 3. Grant BF, Dawson DA: Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. Journal of substance abuse. 1997, 1:103-10. 10.1016/s0899-3289(97)90009-2. 4. National Institute on Alcohol Abuse. Special Report to the US Congress on Alcohol and Health from the Secretary of Health and Human Services. National Institute on Alcohol Abuse and Alcoholism. 1997, 5. Von Knorring AL, Bohman M, von Knorring L, Oreland L: Platelet MAO activity as a biological marker in subgroups of alcoholism. Acta Psychiatrica Scandinavica. 1985, 72:51-8. 10.1111/j.1600-0447.1985.tb02570.x. 6. Lee GP, DiClimente CC: Age of onset versus duration of problem drinking on the Alcohol Use Inventory. Journal of Studies on Alcohol. 1985, 46:398-402. 10.15288/jsa.1985.46.398. 7. Irwin M, Schuckit M, Smith TL: Clinical importance of age at onset in type 1 and type 2 primary alcoholics. Archives of general psychiatry. 19901, 47:320-4. 10.1001/archpsyc.1990.01810160020003. 8. Varma VK, Basu D, Malhotra A, Sharma A, Mattoo SK: Correlates of early-and late-onset al.cohol dependence. Addictive behaviors. 1994, 19:609-19. 10.1016/0306-4603(94)90016-7. 9. Manjunatha N, Saddichha S, Sinha BN, Khess CR, Isaac MK: Chronology of alcohol dependence: Implications in prevention. Indian Journal of Community Medicine. 2008, 33:233-7. 10.4103/0970-0218.42375. 10. Joseph J, Varghese A, Vijay VR, et al.: The prevalence of alcohol use disorders using alcohol use disorders identification test (AUDIT) in the Indian setting: a systematic review and meta-analysis. Journal of Ethnicity in Substance Abuse. 20241, 23:2-0. 10.1080/15332640.2022.2056105. 11. World Health Organization: ICD-10: International Statistical Classification of Diseases and Related Health Problems: Tenth Revision, 2nd Edition. World Health Organization, Geneva, Switzerland; 2004. 12. Pal HR, Jena R, Yadav D: Validation of the Alcohol Use Disorders Identification Test (AUDIT) in urban community outreach and de-addiction center samples in north India. Journal of studies on alcohol. 2004, 65:794-800. 10.15288/jsa.2004.65.794. 13. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM: Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-AR). Br J Addict. 1989, 84:1353-7. 10.1111/j.1360-0443.1989.tb00737.x. 14. Rosa-Oliveira LQ, Presti Pde F, Antunes IR, et al.: Reliability and dimensionality of the Short Alcohol Dependence Data (SADD) questionnaire in a clinical sample of hospitalized patients: using the SADD in a general hospital setting. Braz J Psychiatry. 2011, 33:68-71. 10.1590/S1516-44462010005000020 15. Maxwell ME: Manual for the Family Interview for Genetic Studies (FIGS). National Institute of Mental Health; Clinical Neurogenetics Branch. 1992, 16. Latcham RW: Familial alcoholism: Evidence from 237 alcoholics. The. British Journal of Psychiatry. 1985, 147:54-7. 10.1192/bjp.147.1.54 17. DeWit DJ, Adlaf EM, Offord DR, Ogborne AC: Age at first alcohol use: a risk factor for the development of alcohol disorders. American Journal of Psychiatry. 2000, 157:745-50. 10.1176/appi.ajp.157.5.745. 18. Pitkänen T, Lyyra AL, Pulkkinen L: Age of onset of drinking and the use of alcohol in adulthood: a follow-up study from age 8-42 for females and males. Addiction. 2005, 100:652-61. 10.1111/j.1360-0443.2005.01053.x. 19. Grant BF: The impact of a family history of alcoholism on the relationship between age at onset of alcohol use and DSM-IV alcohol dependence: Results from the National Longitudinal Alcohol Epidemiologic Survey. Alcohol Health Res World. 1998, 22:144. 20. Johnson PR, Banu S, Ashok MV: Severity of alcoholism in Indian males: Correlation with age of onset and family history of alcoholism. Indian J Psychiatry. 2010, 52:243-9. 10.4103/0019-5545.70977. 21. Hingson RW, Heeren T, Winter MR: Age at drinking onset and alcohol dependence: age at onset, duration, and severity. Archives of pediatrics & adolescent medicine. 20061, 160:739-46. 10.1001/archpedi.160.7.739. 22. Reboussin BA, Song EY, Shrestha A, Lohman KK, Wolfson M: A latent class analysis of underage problem drinking: Evidence from a community sample of 16-20 year olds. Drug and alcohol dependence. 2006, 27:199-209. 10.1016/j.drugalcdep.2005.11.013. 23. Kaprio J, Koskenvuo M, Langinvainio H, Romanov K, Sarna S, Rose RJ: Genetic influences on use and abuse of alcohol: a study of 5638 adult Finnish twin brothers. Alcoholism: Clinical and Experimental Research. 1987, 11:349-56. 10.1111/j.1530-0277.1987.tb01324.x. 24. Kaprio J, Viken R, Koskenvuo M, Romanov K, Rose RJ: Consistency and change in patterns of social drinking: a 6-year follow-up of the Finnish Twin Cohort. Alcoholism: Clinical and Experimental Research. 1992, 16:234-40. 10.1111/j.1530-0277.1992.tb01369.x. 25. Prescott CA, Hewitt JK, Heath AC, Truett KR, Neale MC, Eaves LJ: Environmental and genetic influences on alcohol use in a volunteer sample of older twins. Journal of Studies on Alcohol. 1994, 55:18-33. 10.15288/jsa.1994.55.18. 26. Pickens RW, Svikis DS, McGue M, Lykken DT, Heston LL, Clayton PJ: Heterogeneity in the inheritance of alcoholism: A study of male and female twins. Archives of general psychiatry. 19911, 48:19-28. 10.1001/archpsyc.1991.01810250021002. 27. Hill SY, Yuan H: Familial Density of Alcoholism and onset of adolescent drinking. J Stud Alcohol. 1999, 60:7-17. 10.15288/jsa.1999.60.7 28. Hill SY, Locke J, Lowers L, Connolly J: Psychopathology and achievement in children at high risk for developing alcoholism. Journal of the American Academy of Child & Adolescent Psychiatry. 19991, 38:883-91. 10.1097/00004583-199907000-00019. 29. Hill SY, Shen S, Lowers L, Locke J: Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism. Biological psychiatry. 2000 Aug 15. 48:265-75. 10.1016/s0006-3223(00)00841-6.