The observational study was conducted at Department of Psychiatry and De-addiction centre of Acharya Vinoba Bhave Rural Hospital (Jawaharlal Nehru Medical College, DMIMS), Sawangi, in the city of Wardha, Maharashtra over a period of two years (from September 2016 to August 2018). The patients diagnosed with Alcohol dependence syndrome (ADS) as per International Classification of Disease-10^th Edition (ICD-10) Diagnostic Criteria for Research (World Health Organisation, 1993) criteria [28], using alcohol for past 12 months, having difficulties in controlling substance taking behaviour, a physiological withdrawal state and evidence of tolerance i.e., increased doses of the psychoactive substance are required in order to achieve effects originally produced by lower doses; between ages 18 to 65 years; and willing to participate in study were selected through simple random sampling. Those with liver diseases due to illness other than alcoholism, serious physical comorbidities, substance abuse other than alcohol or any other dysfunction interfering with assessment were excluded. The patients were admitted in psychiatric unit and detoxified for alcohol over a period of about two weeks. The participants were also assessed after detoxification phase at around fourth week of abstinence for psychiatric comorbidities. The approval was taken from Institutional Ethics Committee (DMIMS DU/IEC/2016-2017/3020). The participants were informed about study and written consent was obtained.

The sample size was determined using the standard formula 4 pq/L² where p=prevalence of psychiatric morbidities among alcohol dependence individuals, q=100-p and L=allowable error. Considering the 54% of psychiatric morbidities for this research [29], therefore p=54, q=46 and L=20% of p, sample size thus found to be 85. Hence, it was rounded off and subjects’ loss to follow-up (10%) when considered, finally sample size of 100 was included.

The analysis was done by descriptive and inferential statistics. Chi-square test was used to find out association between different variables. Further data were analysed with SPSS version 22.0 and considering p-value <0.05 as significant.

Total 100 patients of Alcohol Dependence Syndrome as per ICD-10 were selected in the present study. There were 99 males and only 1 female with majority of the patients between 26 to 35 years of age (43%) followed by 36 to 45 years (28%), >45 years (19%) and <25 years (10%). There were 81% Hindu, 13% Buddhist and 6% Muslim. Most of the patients were educated upto primary school (50%); employed (75%); and belonged to lower socio-economic status (53%) and nuclear family (53%). Socio-demographic characteristics further reported that majority of them were married (73%) for >10 years (44%) and coming from rural (44%) region. Among study participants 27% and 25% had past and family history of psychiatric disorders, respectively [Table/Fig-1].

The overall prevalence of psychiatric comorbidities as per MINI-PLUS among ADS patients was 49%. Broadly, following diagnostic categories were found: mood disorders-21%, anxiety disorders-13%, adjustment disorders-2%, psychotic disorders-8%, antisocial personality disorder-10% and somatoform disorder-1% [Table/Fig-2].

In the present study, severity of ADS as measured on SADQ revealed 10% mild, 38% moderate and 52% severe levels of dependence respectively. While, hepatic enzyme levels at the time of detoxification were found to be higher for ALT (38%), AST (69%), GGTP (79%), Bilirubin (30%) and Alkaline phosphatase (33%), respectively [Table/Fig-3].

The significant difference was reported between GGTP and psychiatric comorbidities among ADS patients (p<0.05) whereas, hepatic enzymes such as ALT, AST, Bilirubin and Alkaline phosphatase had no significant difference (p>0.05) [Table/Fig-4].

Further the significant difference were found between severity of ADS and hepatic enzymes ALT, AST and GGTP (p<0.05) While, Bilirubin and Alkaline phosphatase reported no significant difference (p>0.05) [Table/Fig-5].

The present study was a hospital based study and aimed at determining the relationship of liver enzymes with severity of dependence and psychiatric comorbidities among ADS. In the present study out of 100 patients selected, 99% were males and 1% was female. This may be due the fact that alcohol use by females was socially unacceptable in this region and most of them do not seek treatment openly in the general hospital setting.

The overall prevalence of one or more psychiatric comorbidities among ADS patients on MINI PLUS was found to be 49% and there was more than one psychiatric diagnosis at a time in many patients in this study. This finding is similar to a study by Singh A et al., who reported psychiatric morbidity of 47% among ADS patients [33]. However, some researchers have also reported higher psychiatric morbidities in Alcohol Dependence Syndrome. Vohra AK et al., and Aswal S et al., in their studies reported psychiatric morbidities of 54% and 76.6% in Alcohol dependent patients [15,29]. As per previous literature, the prevalence of psychiatric comorbidity reported to range from 57% to 84% [21-23].

In the present study Mood disorders were found to be the most common psychiatric comorbidities which included Major Depressive Disorder (MDD) (5%), Suicidality (4%), Dysthymia (2%), MDE with Melancholic features (5%), Substance induced mood disorder (5%). Overall 15% had depressive disorders among selected ADS patients which were main Mood disorders. This finding is in accordance with that of Singh A et al., who demonstrated 24% prevalence of Mood disorder with 16% depressive disorders among alcohol dependent patients [33]. Many researchers reported higher prevalence of depression among ADS patients in their literature like Singh HN et al., (26%), Alec R et al., (33%), Cadoret R et al., (39%), Kakunje A (19%) and Shakya DR et al., (18.3%) [14,34-37]. Prevalence of anxiety disorders reported 13% in our study which included Generalised anxiety disorder (4%), Panic disorder (5%), Social anxiety disorder (SAD) (3%), Obsessive compulsive disorder (1%). Previous researchers such as Echeburua E et al., reported 10.1% Panic disorder, 7.6% GAD and 0.6% OCD; Singh HN et al., reported 16% Phobia, 5% Panic disorder, 8% GAD and 2% OCD; Gauba D et al., reported 17.5% Panic disorder, 13.8% GAD, 10% Phobia and 3.8% OCD; while Singh A et al., reported 6% Panic disorder, 3% SAD, 2% GAD, 1% OCD and 2% Mixed anxiety depressive disorder among alcohol dependent subjects in their studies [14,33,38,39].

The present study also reported 8% psychotic disorders which included Schizophrenia (1%), Substance induced psychotic disorder (4%), Delusional disorder (1%), BPAD I with psychotic features (2%) and 10% ASPD. Almost similar finding was mentioned by Singh A et al., in his research [33]. Whereas others such as Singh HN et al., demonstrated 4% Schizophrenia spectrum disorder and 8% Personality disorder; Aswal S et al., reported 2% Schizophrenia and 21% ASPD; Gauba D et al., reported 2.5% Schizophrenia and 15% ASPD in patients of alcohol dependence [14,29,39]. The differences in prevalence of psychiatric comorbidities may be due to factors like the context (whether the study is conducted in inpatients, outpatients or community sample), stage of illness (whether the evaluation was done during active use or remission), the tools used (whether a structured interview schedule was used or not) and differences in sample size [18,33].

Further, our study demonstrated severe level of dependence (52%) in most of the participants whereas; others reported moderate level (77%) and severe level of dependence in majority of alcohol dependent subjects in their respective research [33,40]. Most of the patients had increased serum levels of AST (69%), GGTP (79%) and Alkaline phosphatase (33%) while, serum levels of ALT (62%) and Bilirubin (70%) were normal at the time of detoxification in present study. This finding is confirmed by previous studies which reported elevated levels of ALT, AST and GGTP levels in alcohol dependent individuals upon admission [9,41]. Our results also found significant correlation between SADQ scores and liver enzymes such as ALT, AST and GGTP. Pradeep RJ et al., also reported significant association between total SADQ scores and ALT; and correlation of withdrawal relief drinking sub-score of SADQ with total bilirubin and AST/ALT ratio [42]. This supports the idea that severity of dependence is associated with the liver dysfunction. The above differences in results could be attributed to heterogeneity of the population under study and tools used for measurement.

The significant correlation was obtained between GGTP and psychiatric comorbidities with high levels among MDD, MDE with Melancholic features, Panic disorder and Substance induced mood disorder in present study. It has been found that increased serum levels of hepatic enzymes upon admission were significantly reduced at the end of detoxification phase. In addition the psychological symptoms were found to be improved after detoxification period in alcohol dependent individuals [9]. Liappas IA et al., found statistically significant correlation between ASAT and Hamilton Depression Rating Scale (HDRS) upon admission; ASAT and Hamilton Anxiety Rating Scale (HARS) at the end of detoxification; and γGT levels and HARS at the end of detoxification period. Gauba D et al., also reported significant association between psychiatric morbidity and mean GGTP-value only. This suggests that liver function profile is related to mood status of alcohol dependent patients, in the sense that liver damage is enhanced and mood deteriorates as the alcohol consumption increases [39,43]. It has been hypothesised that co-occurrence of liver cirrhosis may affect the Hypothalamic Pituitary Thyroid axis (HPT) dysfunction in alcohol abuse. Alcohol abuse frequently produces considerable reductions in triiodothyronine (T3) levels and modest decrease in serum thyroxine (T4) levels. Many alcohol abusing individuals have an increased thyroid hormones binding capacity, evidenced by increased thyroxin-binding globulin level and decreased T3 uptake level. Thyroid hormone dysfunctions found to influence mood symptoms of affected individuals. Thyroid abnormalities in alcohol dependent persons can possibly reflect the influence of liver disease [43]. There is a paucity of research on association of liver enzymes with psychiatric comorbidities and dependence severity among alcohol dependent individuals which is addressed in this research.

The limitations of our study are that it was a hospital based cross-sectional study and only inpatients were included and hence the results cannot be generalised. The sample size was small and other personality disorders were not assessed. These issues need to be addressed in future research with bigger sample size, control groups, inclusion of other laboratory parameters such as T3, fT3, T4, fT4, TSH and more structured interviews.

The prevalence of psychiatric comorbidities among ADS was found to be high comparable to previous research. Mood disorders were found to be most common psychiatric diagnosis. The statistically significant association was found between hepatic enzymes and SADQ scores; and between psychiatric morbidities and hepatic enzymes suggesting that liver function profile may alter the mood status of ADS patients. Hence, these factors need to be taken into consideration at the time of managing alcohol dependent persons for relapse prevention, to improve poor compliance, better outcome and policy making in patients suffering from alcoholism.