The Lack of Influence of Homozygous Long Allele of the 5-HTTLPR Gene on the Severity of Alcohol Craving During 6 Weeks of Rehab Hospitalisation in Comparison to Not Homozygous and Homozygous Short Alleles – Preliminary Report

Figures & data

Table 1 Comparison of Selected Clinical and Psychological Variables in Relation to Allelic Variants in the 5-HTTLPR Gene Polymorphism

Variables	(1)	(2)	(3)	P
	5-HTTLPR Gene Polymorphism (Short/Short or Short Allele) n=18	5-HTTLPR Gene Polymorphism (Long/Short Allele) n=62	5-HTTLPR Gene Polymorphism (Long/Long or Long Allele) n=50
	Median (min-max) or number (%)	Median (min-max) or number (%)	Median (min-max) or number (%)
Age (years)	43.5(27.0–57.0)	44.0 (27.0–67.0)	40.5(24.0–78.0)	0.115
Sex
Women	1(5.6%)	5(8.1%)	6(12.0%)	0.654
Men	17(94.4%)	57(91.9%)	44(88.0%)
Length of alcohol dependence (years)	11.5(3.0–30.0)	15.0(2.0–40.0)	11.5(1.0–30.0)	0.140
SADD (score)	22.5(6.0–35.0)	21.0(7.0–37.0)	24.0(0.0–38.0)	0.331
BDI (score)	14.5(2.0–31.0)	17.0(0.0–51.0)	15.0(0.0–47.0)	0.733
GGT (U/l)	73.00 (25.0–227.0)	68.50 (10.0–611.0)	67.00 (19.0–1495.0)	0.998
Psychopharmacotherapy
Antiepileptics*	2(20.0%)	2(9.5%)	2(15.4%)	0.712
Antidepressants*	2(20.0%)	2(9.5%)	5(38.5%)	0.127
Antianxiety medications*	3(30.0%)	1(4.8%)	3(23.1%)	0.140
Antipsychotics medications*	4(40.0%)	6(28.6%)	5(38.5%)	0.759
Mental disorders (response of patients)	5(29.4%)	17(27.4%)	23(46.0%)	0.107
Depression (response of patients)	3(17.6%)	5(8.1%)	11(22.0%)	0.110

Notes: Chi² test and Kruskal–Wallis test and Games-Howell post hoc test, *Group size for frequency of pharmacotherapy - columns: (1) n=10, (2) n=21, (3) n=13.

Table 2 The Comparison of the Intensity of Alcohol Craving During 4 Weeks of Hospitalisation of Alcohol-Dependent Patients and the Gene Polymorphisms (2A). The Changes of the Intensity Alcohol Craving Between the First and Second Study According Gene Polymorphism – Detailed Analysis (2B)

(A) Comparison of the intensity of alcohol craving measured with the PACS scale during hospitalisation of alcohol-dependent patients according to allelic variants of the 5-HTTLPR gene polymorphism.
Variables		Severity of alcohol craving in the first 2 weeks of hospitalisation PACS score Median (min-max)	Severity of alcohol craving at week 6 of hospitalisation PACS score Median (min-max)	p
	N	AFTER 4 WEEKS
Patients with 5-HTTLPR gene polymorphism (short/short or short allele)	18	5.0(0–15)	2.5(0–7)	0.033
Patients with 5-HTTLPR gene polymorphism (long/short allele)	62	5.0(0–24)	4.0(0–15)	0.002
Patients with 5-HTTLPR gene polymorphism (long/long or long allele)	50	5.0(0–24)	4.5(0–19)	0.242
(B) Differences in PACS results between “study I” and “study II” (detailing the results of Table 2A)
5-HTTLPR gene polymorphism	N	T	Z	p
Total	58	532.500	2.501	0.012
Short/short or short allele	10	5.000	2.293	0.022
Long/short allele	30	130.000	2.108	0.035
Long/long or long allele	18	82.000	0.152	0.879

Notes: Wilcoxon test; N - number of subjects; p - probability level p; T - sum of ranks; Z - Z function of the U statistic; out of 130 subjects analysed, the result for 58 was statistically significant. These should be interpreted as follows according to the rule - “for this many people the result improved and for this many the result worsened”, ie for the short/short polymorphism, for 9 people the result improved and it worsened for 1 (% of total). For short/long, there was an improvement for 22 and for 8 a worsening (% of total). For long/long no change with an improvement for 10 and no improvement for 8 (% of total).

Figure 1 Shows the percentages of people with mild, moderate and severe alcohol craving (according to the PACS scale) divided into three subgroups with respect to the 5-HTTLPR polymorphism. 1 Measurement of severity of alcohol craving at the start of treatment (in the first 2 weeks of hospitalisation); 2- measuring the severity of alcohol craving 4 weeks after the first examination. Illustration of the percentage incidence of PACS results in the three subgroups by descriptive statistics - no statistical tests were used here.

Table 3 An Attempt to Assess Whether, in Addition to the 5-HTTLPR Gene Polymorphism, Other Factors Were Associated with Changes in the Severity of Alcohol Craving (3A) and the Model of the Intercorrelation of These Variables (3B)

(A) Univariate significance tests for the variable occurrence of PACS performance improvement (parameterisation with sigma-constraints; effective hypothesis decomposition)
Effect							SS		df	MS	F	p
Free expression							0.870		1	0.870	3.854	0.052
5-HTTLPR Polymorphism							1.176		1	1.176	5.212	0.024
Sex							0.001		1	0.001	0.005	0.944
Age							0.434		1	0.434	1.923	0.168
SADD (score)							0.946		1	0.946	4.190	0.043
BDI (score)							0.186		1	0.186	0.823	0.366
Error							27.536		122	0.226	-	-
(B) SS test for full model against SS for residuals (sum) - improvement
Dependent variable	Multiple R	Multiple R^2	Corrected R^2	SS Model	df Model	MS Model	SS Rest	df Rest		MS Rest	F	p
Improvement	0.349	0.122	0.086	3.831	5	0.766	27.536	122		0.226	3.395	0.007

Notes: (Part A) The one-dimensional significance tests and (Part B) Multiple linear regression test; legend: SS - sum of squares of effects; df - number of degrees of freedom; MS - mean sum of squares of effects; F- F-test value; p- probability level p; R- coefficient of multiple correlation; R² - coefficient of multiple determination; SS Rest - residual sum of squares; MS Rest - residual mean of squares.

Figure 2 Alcohol craving severity scores (PACS scale scores) in depending on the type of polymorphism of the 5-HTTLPR gene (“0” - subjects with the short/short or short alleles; “1” - individuals with alleles of short/long; “2”- subjects with long/long or long alleles) in alcohol-dependent patients tested (improvement means low alcohol craving severity scores; the decrease in PACS scores obtained by the subjects after 4 weeks of treatment compared to the first test of severity of alcohol craving with the PACS scale is presented as an improvement; the decrease in scores is included as a percentage of the decrease in relation to the original PACS values and compared between patient groups. 5-HTTLPR polymorphism; Expected marginal averages. Current effect: F (2, 127)=2.9747, p=0.05463. Decomposition of effective hypotheses. Vertical bars indicate 0.95 confidence intervals.

Figure 3 Alcohol craving severity scores (PACS scale score) in relation to severity of alcohol dependence (SADD scale score) in surveyed alcohol-dependent patients (improvement indicates low alcohol craving severity scores). Improvement; Expected marginal averages. Current effect F (1, 127)=6.5383, p=0.01173. Decomposition of effective hypotheses. Vertical bars indicate 0.95 confidence intervals. Improvement (Yes) - is a decrease in PACS value. No improvement (No) - no decrease or increase in PACS value.