|DR. AK KALA AWARD PAPER
|Year : 2018 | Volume
| Issue : 1 | Page : 19-24
The clinical, personality, and genetic correlates of binge drinking: A controlled association study from India
Abhishek Ghosh1, Savita Malhotra2, Debasish Basu1, Madhu Khullar3
1 Department of Psychiatry, Drug De-addiction and Treatment Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||2-Nov-2018|
Department of Psychiatry, Drug De-addiction and Treatment Centre, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Background and Objectives: Reasonable amount of literature has been accumulated over the years to indicate that the binge drinkers might be different from the group which does not have any history of binging. Only a handful of research demonstrated genetic predisposition for binging. Materials and Methods: This was a clinic-based association study with a case–control design. Two hundred and ten alcohol dependence cases were recruited. Binge drinking was diagnosed using Semi-structured Assessment for Genetics of Alcoholism-II-. Structured instruments were used for the assessment of impulsivity, and novelty seeking traits. single nucleotide polymorphism genotyping was done using Taqmann assay by real-time quantitative polymerase chain reaction (q-PCR) using Taqman assay (ABI 7500) fast real-time PCR system. Results: Comparison of clinical characteristics revealed an earlier age of onset of alcohol use and dependence, significantly more number of accidental injuries, emotional problems, and history of delirium tremens among the binge drinking group. The mean score in the extravagance subscale, overall novelty seeking scale, subscales of nonplanning, and attentional impulsiveness were significantly more among the binge drinkers. With regard to the candidate gene polymorphism (rs25531), short (S) allele of serotonin transporter was observed to be associated with the binge drinking group. Conclusion: Association of impulsiveness and novelty seeking is a new and important finding, indicating the role of personality traits to increase the vulnerability toward binge drinking. The association with the S allele, although is a replication of previous results, is nevertheless important as our study is from a different ethnic population.
Keywords: 5HTTLPR gene, binge drinking, candidate gene, polymorphism
|How to cite this article:|
Ghosh A, Malhotra S, Basu D, Khullar M. The clinical, personality, and genetic correlates of binge drinking: A controlled association study from India. J Mental Health Hum Behav 2018;23:19-24
|How to cite this URL:|
Ghosh A, Malhotra S, Basu D, Khullar M. The clinical, personality, and genetic correlates of binge drinking: A controlled association study from India. J Mental Health Hum Behav [serial online] 2018 [cited 2019 Sep 21];23:19-24. Available from: http://www.jmhhb.org/text.asp?2018/23/1/19/244913
| Introduction|| |
Although originally the word “binge” means an excessive amount of drinking after a period of abstinence, over the years in epidemiological and experimental research, the connotation of the word has changed from an isolated episode of heavy drinking to a behavioral pattern., About a decade ago, National Institute of Alcohol Abuse and Alcoholism (NIAAA, 2004) proposed an official definition of “binge drinking” as a pattern of drinking alcohol that brings blood alcohol concentration to 0.08 g% or above (≥5/4 for men/women in 2 h) on more than one occasion within the past 6 months. Among school students across 14 European countries in 2011, 41% reported past-month “binge” drinking; levels in the UK were 54%. One in five Australian males and females 16–24 years reported drinking 20+ and 11+ standard drinks in a session (each 10 g alcohol), respectively, at least monthly in the past year. Binge drinking contributes to a substantial portion of alcohol-related deaths. This type of drinking also is associated with alcohol poisoning, unintentional injuries, suicide, hypertension, pancreatitis, sexually transmitted diseases, and meningitis. It underlies many negative social costs, including interpersonal violence, drunk driving, and lost economic productivity. Perhaps, these could be indicative of a severe form of alcohol use disorder. Moreover, among those having binge drinking in the adolescence, ~1 in 3 qualifies (3 in 5 in frequent binge drinkers) for the diagnosis of alcohol abuse and ~1 in 17 (1 in 5 for frequent binge drinkers) qualifies for alcohol dependence (AD) in the adulthood. These facts might allude to the possibility that binge drinking could not only be a distinctive behavioral phenotype for the severity of alcohol use but could also be a marker of vulnerability for future AD. Research had demonstrated a significant difference between the binge drinking and the nonbinge drinking group with regard to alcohol expectancies, perception of drunkenness, tolerance to alcohol, and social circumstances of drinking. Studies on cognitive neuro-psychology showed that the binge drinking group had more impairment in working memory, and executive function. Neuroimaging results focussing on the brain metabolism and white matter density had found out a corresponding decrease in neural integrity and deficit in the frontal white matter volume. Neurophysiological research on P300 amplitude which is a marker of attention and memory operations has been found to be smaller among the binge drinker. Hence, reasonable amount of literature has been accumulated over the years to indicate that the binge drinkers might be different from the group which does not have any history of binging. However, the difference shown so far might also be due to the effect of binging on the brain and subsequently on the behavior, which precludes the possibility that the binge drinkers are “inherently different” from the nonbinge drinkers. Family studies, genetic studies or studies of personality traits could address this important issue. So far, there is only handful research in this area, which indicates the possible involvement of serotonin transporter (5HTT) and alcohol dehydrogenase 2 gene polymorphism in binge drinking. Moreover, the frequency of binge drinking has been found to be significantly different across various ethnic groups, which further indicates the possibility of genetic influence on binge drinking.,
Most of the studies conducted so far in this area have focussed on the adolescent population with mixed ethnicity. To the best of our knowledge, no studies had explored for the difference in the personality traits like impulsivity and novelty seeking which are otherwise demonstrated as important markers of a particular subtype of AD or in general externalizing spectrum. Moreover, these traits are more inherent in nature and have been found to be mediated by genetic factors. Taking cues from the previous research and the existing lacunae, the current paper attempted to explore the clinical, personality and genetic correlates for binge drinking by comparing this group with the nonbinge drinking group.
| Materials and Methods|| |
This was a clinic-based study utilizing cases of AD. In this study, 210 alcohol dependent male patients, attending the Drug De-addiction and Treatment Centre, Department of Psychiatry, PGIMER, Chandigarh were enrolled by purposive sampling. This tertiary care Institute caters to a population from all the northern states of India and some Western states. The data were gathered for the purpose of candidate gene polymorphism study in AD. This project was funded by the Indian Council of Medical Research. The primary results were discussed in a paper which has been accepted for publication in the Indian Journal of Medical Research. Cases with a history of any other substance abuse/dependence other than nicotine were excluded. Cases with mental retardation, or having psychosis, bipolar disorder were also excluded from the study. The study period was from September 2010 to August 2012. AD was diagnosed by administration of a semi-structured interview by a trained clinician using modified version of Semi-structured Assessment for Genetics of Alcoholism-II (SSAGA-II). This interview generated lifetime diagnosis of AD according to the nternational Classification of Diseases Tenth Edition as well as Diagnostic and Statistical Manual Fourth Edition. “Binge drinking” was diagnosed with the help of question no. 16B which indicates a lifetime history of binge drinking (amount as defined in the NIAAA, 2004) for more than 3 times. It was ensured that all these binging episodes must have happened before the onset of AD. In positive cases, whenever possible and available, the diagnosis of binging was cross checked from the family members. Semi structured instrument, SSAGA-II has been administered for all subjects for the assessment of alcohol use disorders. Barratt impulsiveness scale was administered for measuring impulsivity. It has a total score of 30 and contains three subscales related to impulsiveness., The first measures motor impulsiveness and lack of perseverance. The second measures cognitive impulsivity by assessing inattention. The third scale evaluates nonplanning impulsivity by scoring lack of self-control and intolerance of cognitive complexity. Novelty seeking trait was assessed by Temperament and Character Inventory., It has four subscales, namely, exploratory excitability, impulsiveness, extravagance, and disorderliness. Clinical details, including ethnicity, age at first use of alcohol, and quantity of alcohol consumed (ml/day), duration of alcohol use, duration of dependence, and the presence of withdrawal seizures were assessed and recorded. Ethical committee clearance was obtained before recruitment of subjects. All cases gave written informed consent to participate in the study.
Genomic DNA extraction and genotyping
Intravenous blood samples (about 6 ml each) were collected in sterile ethylenediaminetetra-acetic acid-coated vacutainers and stored at −20°C until processing for DNA extraction was carried out. DNA was isolated from whole blood using the standard organic method (phenol-chloroform-isoamyl). Single nucleotide polymorphism (SNP) genotyping for all the polymorphisms analyzed in this study was done using ABI Taqmann assay kits (Life Technologies) by real-time quantitative polymerase chain reaction (q-PCR) on ABI 7500 fast real-time PCR system. The oligonucleotide sequence of the probes for different candidate genes studied is described in [Table 1].
Statistical analysis between cases and controls with different genotypic profiles for different candidate gene polymorphisms was performed using the IBM (Chicago, Illinois: SPSS Inc. 2003). Discrete and continuous variables between cases and controls were compared using Pearson's Chi-square test and unpaired t-test as appropriate. The genetic association of binge drinking with different candidate genes in relation to polymorphic prevalence was evaluated using Chi-square test. Power analysis was performed using Quanto (Version 1.0) (University of South California, USA) (http://hydra.usc.edu/gxe). Genotype distributions were tested for deviation from the Hardy–Weinberg Equilibrium proportions using the HWSIM program.
| Results|| |
Comparison of clinical characteristics between the binge drinking and nonbinge drinking group has revealed a significant difference in the mean age of first drink (P < 0.05) and age of onset of dependence (P = 0.03). Comparison with Chi-square test also has demonstrated significant difference between the groups with regard to accidental injuries for >3 times due to drinking (P = 0.003), continued to drink despite having emotional problems (P = 0.003), drinking mainly to relieve withdrawal symptoms (P = 0.03), and presence of delirium tremens (P = 0.05). However, there was no difference with respect to continue to drink despite serious physical ailments (P = 0.06) and presence of withdrawal seizures (P = 0.6) [Table 2].
|Table 2: Comparison of clinical characteristics of binge and nonbinge drinkers|
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Comparison of the mean of total scores and scores on various subscales of novelty seeking scale and Barratt's impulsiveness scale (BIS) has been done. Among the various subscales of the novelty seeking scale, the mean score of extravagance was significantly more (P = 0.01) in the binge drinkers as compared to the nonbinge drinkers. The total score in the novelty seeking scale was also significantly more (P = 0.04) among the binge drinking group. However, the differences in the mean scores of other subscales were not statistically significant. The binge drinking group had scored significantly more in the nonplanning impulsiveness (P = 0.01) and attentional impulsiveness (P = 0.04) subscales of BIS. However, the difference did not reach at the statistical significance level for motor impulsiveness (P = 0.9) and for the total score of BIS (P = 0.1) [Table 3].
|Table 3: Comparison of personality characteristics of binge and nonbinge drinkers|
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The genotype frequencies of studied genes (5'HTTLPR and alcohol dehydrogenase 2 [ALDH2]) in binge drinking and nonbinge drinking groups are shown in [Table 4]. At the genotypic level, the frequency of homozygous genotype (A/A; rs25531) of 5HTTLPR gene showed statistically significant increase in the binge drinker as compared to the nonbinge drinker (Chi-square value = 15.6; P = 0.001). Furthermore when the allele frequency (A vs. G allele aka S vs. L allele) was compared between the two groups, the binge drinking group was significantly associated with the A (also S) allele [Table 5]. As ALDH2 was found to be monomorphic (G/G; rs671) in our population, no comparison could be made between the groups.
|Table 4: Comparison of the genotype frequency of candidate genes between the binge drinker and nonbinge drinking alcohol dependence|
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| Discussion|| |
The present study has compared the clinical characteristics, personality traits and genetic polymorphisms between the binge drinking and the nonbinge drinking alcohol dependent groups. Among various clinical parameters, the binge drinking group was found to have an earlier onset of alcohol use and dependence. This group also had more physical (and also delirium tremens) and emotional complications due to alcohol use and more frequently encountered accidental injuries than the nonbinging alcohol dependent group. The binge drinking group was drinking mostly to relieve withdrawal symptoms. Results with regard to personality traits showed that the binge drinking group had a significantly higher total score in the novelty seeking dimension. Although there was no difference in the total score of impulsiveness scale, the binge drinking group scored higher in the subscales of attentional impulsiveness and nonplanning impulsiveness. Studies on genetic polymorphisms have demonstrated that binge drinkers are more likely to be homozygous for S allele (A/A rs25531) of 5HTT (5HTTLPR).
The clinical characteristics of the binge drinkers are quite in line with the available evidence. Binge drinking has been consistently associated with accidents, episodes of intoxications, and loss of productivity., Binge drinking rates were highest among younger age groups and declined with increasing age. The USA 2001 data showed, young adults aged 21–25 years (18 episodes/person/year) and underage drinkers aged 18–20 years (~15 episodes/person/year) had the highest rates of binge-drinking episodes. This could explain the earlier age of first drink among the binge drinkers in our study population. As already mentioned that binge drinking increases the odd of developing AD by 19 times, the early age of onset of AD among the binge drinking group is understandable. All these together could be an indicator of the severity of AD. Meaning thereby, the binge drinkers are more severely affected by AD as compared to the nonbingeing group.
The association of binge drinking with the novelty seeking dimension of personality trait and with the attentional and nonplanning impulsiveness though not studied till date could be understood on the basis of existing neuro-cognitive research which has consistently demonstrated significantly more attention, memory, and executive dysfunction among the binge drinkers.,, However, as opposed to the neuro-cognitive dysfunction in alcoholics, which could be as a result of the effect of alcohol on the brain, personality traits are inherent and hence preexisting. Therefore, these could be conceptualized as predisposing factors for binge drinking. Behaviorally, involvement in the party centred life and an attitude toward risk taking were shown as risk factors for binge drinking. These patterns of behaviors are reflective of novelty seeking personality. No association with motor impulsiveness and association with non-planning impulsiveness could be an indicator toward higher order brain dysfunction (i.e., executive dysfunction) or the “no-go” circuitry of the brain rather than the “go-circuit.”
The binge drinking group is significantly associated with the homozygous S allele (A/A rs25531) of 5HTTLPR gene. Similar finding has been observed in another study conducted among college students of the US. In addition, those who were homozygous for S allele were found to be drinking more alcohol per occasion and were drinking with the intention to get drunk. The analogous finding has also been reported in alcohol dependent cases from a different ethnic population. Replication of these results in is study further bolsters its validity. 5HTT insertion deletion gives rise to the most common form of SNP in human, namely the S allele and the L allele. These alleles have a functional difference. The S allele variant is associated with lower expression of 5HTT sites and reduced efficiency in 5HT uptake. A higher frequency of S allele was associated with higher ethanol tolerance in young adults (<26 years), suggesting that self-regulation of alcohol intake may be influenced by the presence of this allele. S allele has also observed to be associated with early onset alcoholism. Although in the present study, AD has not been classified according to the age of onset, the binge drinking group which has a significantly lower age of onset of AD is associated with the S allele. In addition, S allele is associated with the group of AD which has a higher number of negative life events and anxiety as a prominent feature, using alcohol for anxiolysis., In our study, emotional problems (includes anxiety, worry, and depression) were significantly more common in the binge drinking group, which is perhaps consistent with the previous finding. Another polymorphism which has been found to be associated with binge drinking is ALDH2. The presence of ALDH2*2 seems to have a protective effect from binge drinking. However, in our sample, ALDH2 gene has been observed to be monomorphic. Hence, the comparison could not be done.
The current research is based on a clinic attending alcohol dependent male. Although the referral clinic attending population which is expected to fall under the severe spectrum of AD served the purpose of the study, this might be responsible for the lack of generalizability. As we have exclusively studied male alcoholics, the results should not be extended to the female population. The diagnosis of binge drinking in our study was based on an item of SSAGA-II and it was made retrospectively. Though to ensure the validity of diagnosis corroboration from the family members was done, the possibility of recall bias could not be ruled out. Although formal power calculation was not done in the present study, it appears reasonable. The threshold of more than three binging episode in the past though might have identified a behavioral pattern of binge drinking, it is still arbitrary. However, despite all these limitations or considerations, the association of impulsiveness and novelty seeking with binge drinking is a new and important finding, indicating the role of personality traits to increase the vulnerability toward binge drinking. The association with the S allele, although is a replication of previous results, is nevertheless important as our study is from a completely different ethnicity. Consistent findings across ethnic groups increase the validity of the same. Future research could endeavor to find out neurobiological and other genetic correlates of binge drinking and if the results consistently show a pattern of significant difference between the binge and nonbinge drinking group, the potential role of this phenotype in the sub-typing of AD could well be considered.
The authors would like to thank Indian Council of Medical Research.
Financial support and sponsorship
Indian Council of Medical Research.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]