Association analysis of the Ex3 VNTR polymorphism of the DRD4 dopamine receptor gene with personality traits in patients with a behavioural addiction

Association analysis of the Ex3 VNTR polymorphism of the DRD4 dopamine receptor gene with personality traits in patients with a behavioural addiction | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association analysis of the Ex3 VNTR polymorphism of the DRD4 dopamine receptor gene with personality traits in patients with a behavioural addiction Agnieszka Boroń, Remigiusz Recław, Krzysztof Chmielowiec, Jolanta Chmielowiec, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4409644/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Results In behavioural and amphetamine addicts with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more frequently compared to the control group with the s/s polymorphism. Conclusions: In the presented study, we see that ad-dictions should be analysed multifactorial. We can conclude that DRD4 and its polymorphic variant influence addiction development. behavioral addiction personality traits DRD4 gene Figures Figure 1 Figure 2 1. Introduction Research on the biology and genetics of addiction has been going on for several decades. Despite many analyses, we still do not know a clear answer to the question of which genetic or epigenetic factors are most responsible for the development and course of ad-diction. However, we know that these are multi-gene and multi-factor entities, particularly related to cerebral neurotransmission, and it is justified to analyse these factors simultaneously. To better understand the co-occurrence of addictions and internalising syndromes such as depression, studies examining dopaminergic polymorphisms may be particularly promising. Influential theoretical propositions such as "reward deficiency syndrome" [ 1 ] suggest that variants of the D2 dopamine-like receptor genes make some individuals less likely to experience rewards from everyday activities, leading to general dysphoria and seeking more significant sensations with sub-stance abuse. Therefore, studies have associated dopaminergic polymorphisms with externalising and internalising syndromes [ 2 , 3 ]. In the present study, we specifically looked at the polymorphism of the DRD4 dopamine receptor gene, which is widely described in the literature as associated with sensation seeking. This applies to both people who abuse substances and those who suffer from mood disorders [ 4 ]. Substance use disorder (SUD) is also known as drug use disorder, in which the misuse of one or more substances leads to the inability to work to control the use of the drug or medications. SUD is characterised by mental, physical and behavioural impairment [ 5 ]. SUD is also defined as a multifactorial disorder, de-pending on several causes, such as individual genetic background − 40 to 60% of susceptibility to SUD and environmental factors, including peer pressure, emotional anxiety, and depression [ 6 ]. It is important to remember that genes alone do not determine the ad-diction phenotype. Environmental factors also play an important role. In general, the initiation and use of substances during adolescence are largely influenced by common environmental factors, although genetic factors and specific environmental factors also play a role. At later ages and with more rigorous measures of substance use, individual differences between people can only be explained by genetic factors and unique environmental factors. This pattern seems logical because in early adolescence, teenagers tend to have fewer opportunities to express their genetic predispositions because most of their actions and decisions are influenced by people in positions of authority (such as parents). As teenagers move into adulthood and typically leave the social structure of their youth, they have more opportunities to express their genetic predispositions, choosing more freely among friends, activities, and environments [ 7 ]. When considering possible genetic risk factors for SUD, new molecular techniques have been applied to identify candidate genes associated with regulating neurotransmitters and substance metabolism [ 8 , 9 ]. One of the genetic markers is a polymorphic variant in exon III of the dopamine receptor 4 (DRD4) - a variable number tandem repeat (VNTR) [ 10 ]. The DRD4 gene is located on chromosome 11, which encodes a 7-transmembrane G-protein-coupled receptor to which endogenous dopamine responds [ 10 ]. A sequence of 48 base pairs with a repeat range of 2–11 existed. 2, 4 and 7 repeats are considered the most common genotypes that can change receptor sensitivity [ 11 ]. The number of repetitions has a functional effect on the dopamine receptor. For example, seven or more repeats correlated with blunted intracellular and dopamine sensitivity [ 12 , 13 ]. Many biological models can explain substance use, addictive disorders and susceptibility to addiction [ 14 ]. Most models are not mutually exclusive but rather complementary; they investigate various aspects of addictive behaviours, particularly dopaminergic circuits. The mesolimbic dopaminergic system is a neural circuit involving the nucleus accumbens (in the ventral striatum) receiving dopaminergic inputs from the ventral teg-mental area [ 15 ]. This neural circuit is a common reward neural pathway. Do-pa-mine-releasing activity in the nucleus accumbens is associated with reward responsive-ness to both substance-based rewards (e.g., cocaine) and “natural” rewards (e.g., sex, video games). [ 16 ]. Reward-oriented models of addiction focus on reward processing and the reinforcing aspect of drug use. One model posits that repeated exposure to a drug or appetitive behaviour in susceptible individuals can excite these neural circuits and influence hedonic attitudes [ 17 ]. So, over time, addictive behaviours can “take over” the natural system rewards in the brain, in effect making it more sensitive to the primary drug and less sensitive to other "natural" reinforcers/rewards. Dopamine is not the only important neurotransmitter, nor is the midbrain dopaminergic system the only brain area important in models of addiction. Addictive disorders involve dysfunction in the expression and function of a wide range of neurotransmitters and neuropeptides, including glutamate, gamma-aminobutyric acid (GABA), serotonin, norepinephrine, and acetylcholine, as well as corticotrophin-releasing factor, opioids, cannabinoids, oxytocin, vasopressin, and neuropeptide Y [ 18]. Different areas of the brain have also been associated with different stages of the addiction cycle [ 14 ]. While the mid-brain dopaminergic system and its associated dorsal striatum appear to be important in cases of abuse and even intoxication, stress-related neurocircuitry systems, including the extended amygdala and the central and peripheral noradrenergic systems, appear to be responsible for processes relevant to states of negative affect. And withdrawal. The basolateral prefrontal cortex, the amygdala, the insula, and the hippocampus are associated with states of hunger [ 19 ]. However, when considering the neurobiology of addictions, it is necessary to take the psychological factor into account. Recent research has sorted the psychological components of reward processing into domains, including reward expectation and valuation, reinforcement learning, salience attribution, and loss/punishment processing [ 20 – 22 ]. Ber-ridge and Robinson [ 20 ] proposed a motivational model of addiction, which suggests that "liking" (the affective response of feeling pleasure) and "wanting" (stimulus-based motivation) can be separated anatomically and chemically. “Reward Deficiency Syn-drome” is another reward-oriented model of addiction vulnerability that posits that de-creased responsiveness of the midbrain dopaminergic system may lead individuals at risk for sub-stance dependence and addictive disorders to seek out and engage in addictive behaviours to compensate for insufficient arousal. [ 23 ]. The reward deficit model is consistent with drug-based theories of addiction [ 19 , 24 ]. Addiction models include elements of motivation, cognitive control, and decision-making. They argue that addictive disorders may represent misdirected motivation in which relatively greater priority is given to appetitive behaviours, such as drug use, and less to other behaviours, such as work, school, and family care [ 25 – 27 ]. Thus, the motivation to engage in appetitive be-haviour "outweighs" other motivational goals. These models incorporate the neuroeconomic concept of temporal discounting: choosing smaller immediate rewards over larger delayed rewards. These decision-making pathways are associated with distinct brain regions and circuits [ 1 ]. Biologically, the selection of smaller immediate rewards appears to be related to the ventral striatum and ventromedial PFC activity. In contrast, the selection of larger delayed rewards appears to be associated with dorsal prefrontal areas, although the subjective value of immediate or delayed reward may influence the neural response [ 1 , 19 , 28 ]. Since the described factors are related, the present study concerns the analysis of the genetic factor in connection with the psychological factor related to personality. It is known that gambling addiction and substance addiction share similar biological mechanisms and symptoms, therefore our goal in this work is to analyze the DRD4 Ex3 s/s gene polymorphism in patients addicted to gambling and substances compared to healthy controls. The study also assessed personality measured using the NEO-FFI questionnaire and anxiety measured using the STAI questionnaire in all study groups. 2. Materials and Methods 2.1. Participants The study group consisted of 307 volunteers. Of these, 107 addiction behavioural and amphetamine men with three months of abstinence staying in addiction treatment units (mean age = 27.51, SD = 5.25;) and 200 men who were not addicted and had no mental disorders (mean age = 20.20, SD = 4.51;). Addicted people were recruited to addiction treatment centers in the Lubusz Voivodeship. Both groups were examined by the psychia-trist using the Mini-International Neuropsychiatric Interview (M.I.N.I). People with psychotic symptoms and mental disorders other than behavioral and amphetamine addiction were excluded from the study. None of the addicted people received pharmacothera-py. The control group consisted of healthy, non-addicted people without mental disorders and not practicing competitive sports. Both addiction behavioural and amphetamine and the control group undergo the same psychometric testing with the NEO Five-Factor Personality Inventory (NEO-FFI) and State-Trait Anxiety Inventory (STAI) questionnaire. The Bioethics Committee of the Pomeranian Medical University in Szczecin approved the study (KB-0012/164/17-A). All participants gave their written, informed consent before entering the study. All methods were performed in accordance with the relevant guidelines and regulations. Research was performed in accordance with the Declaration of Helsinki. The study was conducted in the Independent Health Promotion Laboratory, Pomeranian Medical University in Szczecin. 2.2. Psychometric tests STAI questionnaire measures anxiety as a trait, which can be described as a persistent predisposition to having worries, stress, and discomfort, and anxiety as a state, which can be described as anxiety, fear, and momentary stimulation of the autonomic nervous sys-tem in response to specific situations. The Personality Inventory (NEO-FFI Five-Factor Inventory, NEO-FFI) contains six components for each of the five traits - neuroticism (anxiety, hostility, depression, self-awareness, impulsivity, susceptibility to stress), extroversion (warmth, sociability, assertiveness, activity, emotion seeking, positive emotions), openness to experience (fantasy, aesthetics, feelings, actions, ideas, values), agreeableness (trust, straightforwardness, al-truism, compliance, modesty, tenderness), conscientiousness (competence, order, duty, striving for achievements, self-discipline, consideration). The results of both inventories, i.e., NEO-FFI and STAI., were reported as the sten scores. The conversion of the raw score to the sten scale was carried out following the Polish standards for adults, where it was assumed that 1–2 sten corresponds to very low results, 3–4 low results, 5–6 average results, 7–8 high results, and 9–10 sten corresponds to very high results. 2.3. Genotyping The genomic DNA was isolated from venous blood by using standard procedures. Geno-typing was conducted with the real-time PCR method. Link to data placed in the repository: https://data.mendeley.com/preview/fcsc5hr4x7?a=cef08628-c0c8-4286-be3c-06f4d1013fd7 2.4. Statistical Analysis A concordance between the genotype frequency distribution and Hardy-Weinberg equilibrium (HWE) was tested using the HWE software ( https://wpcalc.com/en/equilibrium-hardy-weinberg/ (03 December 2023). The relations between DRD4 Ex3 variants: addiction of behavioural and amphetamine and control subjects and the NEO Five-Factor Inventory were analysed using a multivariate analysis of factor effects ANOVA [NEO-FFI/ scale STAI/ × genetic feature × control and addiction of behavioural and amphetamine × (genetic feature × control and addiction of behavioural and amphetamine)]. The condition of homogeneity of variance was fulfilled (Levene test p > 0.05). The analysed variables were not distributed normally. The NEO Five-Factor Inventory (Neuroticism, Extraversion, Openness, Agreeability, and Conscientiousness) sten scores were compared using the U Mann–Whitney test DRD4 Ex3 genotype frequencies between control subjects and addiction of behavioural and amphetamine were tested using the chi-square test. All computations were performed using STATISTICA 13 (Tibco Software Inc, Palo Alto, CA, USA) for Windows (Microsoft Corporation, Redmond, WA, USA). 3. Results These frequency distributions for the DRD4 Ex3 gene accorded with the Hardy-Weinberg equilibrium (HWE) both in the addiction of behavioural and amphetamine and control subjects. In the addiction of behavioral and amphetamine subjects, homozygote reference s/s constituted 72 observations and calculated expected 70.7, heterozygote s/l constituted 30 observations and calculated expected 32.5 and homozygote variant l/l constituted 5 observations and calculated expected 3.7 (χ2 = 0.644; p = 0.4222). In the control group, it was found that homozygote reference s/s constituted 100 observations and calculated expected 94.5, heterozygote s/l constituted 75 observations and calculated ex-pected 85.9 and homozygote variant l/l constituted 25 observations and calculated expected 19.5. (χ2 = 3.239; p = 0.0719, Table 1 .). Table 1 Hardy-Weinberg's equilibrium for the DRD4 Ex3 gene. Hardy-Weinberg equilibrium calculator, including analysis for ascertainment bias Observed (Expected) allele freq χ 2 ( p-value ) DRD4 Ex3 Addiction to behavioral and amphetamine n = 107 s/l 30 (32.5) p (s) = 0.81 q (ll) = 0.19 0.644 (0.4222) s/s 72 (70.7) l/l 5 (3.7) DRD4 Ex3 control n = 200 s/l 75 (85.9) p (s) = 0.69 q (l) = 0.31 3.239 (0.0719) s/s 100 (94.5) l/l 25 (19.5) p– statistical significance χ 2 test. Statistically significant differences were found in the frequency of DRD4 Ex3 genotypes in the tested sample of Addiction of behavioural and amphetamine when compared to the control group. In the subjects, the addiction of behavioral and amphetamine homozygote reference s/s constituted a higher percentage compared to the control group, while a lower percentage was found for hetozygote s/l and for homozygote variant l/l (s / l 0.28 vs s / l 0.37; s / s 0.67 vs s / s 0.50; l / l 0.05 vs l / l 0.12, χ 2 = 9.914, p = 0.0070). Statistically significant differences in the frequency of rs3864236 alleles were found between Addiction of behavioural and amphetamine and the control group. In the addiction of behavioral and amphetamine subjects, the s allele occurred more often compared to the control group, while the l allele occurred less frequently. (s 0.81 vs s 0.69; l 0.19 vs l 0.31, χ 2 = 11.190, p = 0.0008) (Table 2 ). The means and standard deviations of the NEO-FFI results and the STAI state and trait scale for the Addiction of behavioural and amphetamine and control subjects are shown in Table 3 . Table 3 STAI and NEO Five-Factor Inventory sten scores between healthy controls and Addiction of behavioural and amphetamine. STAI/ NEO Five-Factor Inventory/ Addiction to behavioral and amphetamine (n = 371) Control (n = 151) Z (p-Value) STAI trait/scale 6.98 ± 2.30 5.33 ± 2.14 3.106 0.0019* STAI state/scale 5.60 ± 2.61 4.77 ± 2.11 5.575 0.0000* Neuroticism/scale 6.58 ± 2.28 4.76 ± 1.94 6.657 0.0000* Extraversion/scale 5.99 ± 2.18 6.28 ± 2.00 -1.143 0.2529 Openness/scale 4.77 ± 2.02 4.56 ± 1.64 0.765 0.4442 Agreeability/scale 4.28 ± 1.82 5.54 ± 2.04 -4.941 0.0000* Conscientiousness/scale 5.57 ± 2.24 5.62 ± 2.15 0.119 0.9054 p , statistical significance with Mann–Whitney U-test; n , number of subjects; M ± SD, mean ± standard deviation; * statistically significant differences. The Addiction of behavioural and amphetamine compared to the control group obtained higher scores in the assessment of the STAI trait scale (6.98 vs 5.33; Z = 3.106; p = 0.0019), of STAI state scale (5.60 vs 4.77; Z = 5.575; p < 0.0000) and NEO-FFI neuroticism scale (6.58 vs 4.76; Z = 36.657; p < 0.0000). Significantly lower results were obtained for the NEO-FFI agreeability scale (4.28 vs 5.54; Z = -4.941; p < 0.0000). The results of the factorial ANOVA of the STAI trait and state the NEO Five-Factor Personality Inventory, and the State-Trait Anxiety Inventory sten scales are summarised in Table 4 . Significant statistical impact of Addiction of behavioural and amphetamine and DRD4 Ex3 genotype was demonstrated for a score of the STAI trait scale. There was a statistically significant effect of DRD4 Ex3 genotype interaction and Addiction of behavioural and amphetamine or not using (control group) on the STAI trait scale (F 2.301 = 4.85; p = 0.0084; η 2 = 0.031; Fig. 1 .). The power observed for this factor was 80%, and approximately 3% was explained by the polymorphism of the DRD4 Ex3 and Addiction of behavioural and amphetamine or lack thereof on trait extraversion score variance. There was also a statistically significant effect of Addiction to behavioural and amphetamine or the control group on the STAI trait scale score (F 1.301 = 6.44; p = 0.0116; η 2 = 0.021). The power observed for this factor was over 72%, and approximately 2% was explained by Addiction to behavioural and amphetamine or lack thereof on the variance in the extraversion score. Table 5 shows the results of the post hoc test. In behavioural and amphetamine addicts with a higher level of the STAI trait scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in behavioural and amphetamine addicts with a higher level of the STAI trait scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism. Another significant difference worth noting in the post hoc test is that in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to people addicted to behavioural and amphetamine with the polymorphism. DRD4 Ex3 s/l gene. Significant statistical impact of Addiction of behavioural and amphetamine and DRD4 Ex3 genotype was demonstrated for a score of the NEO-FFI Neuroticism scale. There was a statistically significant effect of DRD4 Ex3 genotype interaction and of behavioural and amphetamine or not using (control group) on the Neuroticism scale (F 2.301 = 3.38; p = 0.0354; η 2 = 0.022; Fig. 2 .). The power observed for this factor was 63%, and approximately 2% was explained by the polymorphism of the DRD4 Ex3 and Addiction of behavioural and amphetamine or lack thereof on trait Neuroticism score variance. There was also a statistically significant effect of Addiction to behavioral and amphetamine or the control group on the Neuroticism scale score (F 1.301 = 13.89; p = 0.0002; η 2 = 0.044). The power observed for this factor was over 96%, and approximately 4% was explained by Addiction to behavioural and amphetamine or lack thereof on the variance in the Neuroticism score. Table 5 shows the results of the post hoc test. In behavioural and amphetamine addicts with a higher level of the Neuroticism scale trait, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in behavioural and amphetamine addicts with a higher level of the Neuroticism scale trait, the DRD4 Ex3 s/l gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Noteworthy in the post hoc test is an-other marked significant difference in people addicted to behavioural and amphetamine with a higher level of the Neuroticism Scale trait; the DRD4 Ex3 gene polymorphism s/s occurred significantly more often compared to people addicted to behavioural and amphetamine with polymorphism of the DRD4 gene Ex3 s/l. Table 4 The results of 2 × 3 factorial ANOVA for addiction of behavioural and amphetamine and controls, NEO Five-Factor Inventory, STAI and HINT1 rs3864236. STAI /NEO Five-Factor Inventory Group DRD4 Ex3 ANOVA s/l n = 105 M ± SD s/s n = 172 M ± SD l/l n = 30 M ± SD factor F (p-value) ɳ 2 Power (alfa = 0,05) STAI trait scale Addiction to behavioral and amphetamine (ABA); n = 107 6.23 ± 2.31 7.37 ± 2.27 5.80 ± 1.30 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 868.72 ( p < 0.0001) F 1,301 = 6.44 ( p = 0.0116)* F 2,301 = 0.96 ( p = 0.3829) F 2,301 = 4.85 ( p = 0.0084)* 0.743 0.021 0.006 0.031 1.000 0.716 0.217 0.799 Control (C); n = 200 5.52 ± 2.08 5.09 ± 2.14 5.72 ± 2.26 STAI state scale Addiction to behavioral and amphetamine (ABA); n = 107 5.17 ± 2.67 5.85 ± 2.59 4.60 ± 2.41 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 566.89 ( p < 0.0001) F 1,301 = 0.50 ( p = 0.4784) F 2,301 = 0.10 ( p = 0.9060) F 2,301 = 2.95 ( p = 0.0536) 0.653 0.002 0.001 0.019 1.000 0.109 0.065 0.573 Control (C); n = 200 5.00 ± 1.98 4.47 ± 2.12 5.24 ± 2.31 Neuroticism scale Addiction to behavioral and amphetamine (ABA); n = 107 5.90 ± 2.47 6.90 ± 2.19 5.80 ± 1.79 intercept ABA / C DRD4 Ex3 ABA /C x DRD4 Ex3 F 1,301 = 821.74 ( p < 0.0001) F 1,301 = 13.89 ( p = 0.0002)* F 2,301 = 0.93 ( p = 0.3946) F 2,301 = 3.38 ( p = 0.0354)* 0.792 0.044 0.006 0.022 1.000 0.960 0.211 0.634 Control (C); n = 200 4.96 ± 1.88 4.60 ± 1.85 4.76 ± 2.47 Extraversion scale Addiction to behavioral and amphetamine (ABA); n = 107 6.24 ± 2.26 5.76 ± 2.13 7.80 ± 1.92 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 1139.03 ( p < 0.0001) F 1,301 = 0.51 ( p = 0.4769) F 2,301 = 2.16 ( p = 0.1174) F 2,301 = 2.11 ( p = 0.1233) 0.782 0.002 0.015 0.014 1.000 0.109 0.440 0.431 Control (C); n = 200 6.11 ± 1.91 6.36 ± 1.99 6.52 ± 2.35 Openness scale Addiction to behavioral and amphetamine (ABA); n = 107 4.72 ± 2.20 4.78 ± 1.94 5.00 ± 2.45 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 809.29 ( p < 0.0001) F 1,301 = 0.34 ( p = 0.5584) F 2,301 = 0.23 ( p = 0.7963) F 2,301 = 0.04 ( p = 0.9637) 0.729 0.001 0.002 0.0002 1.000 0.090 0.086 0.056 Control (C); n = 200 4.55 ± 1.53 4.49 ± 1.78 4.88 ± 1.36 Agreeability scale Addiction to behavioral and amphetamine (ABA); n = 107 4.62 ± 1.66 4.25 ± 1.85 2.80 ± 2.05 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 654.27 ( p < 0.0001) F 1,301 = 19.21 ( p < 0.0001)* F 2,301 = 1.61 ( p = 0.2009) F 2,301 = 1.49 ( p = 0.2265) 0.686 0.060 0.011 0.010 1.000 0.992 0.340 0.317 Control (C); n = 200 5.47 ± 2.03 5.63 ± 2.04 5.40 ± 2.18 Conscientiousness scale Addiction to behavioral and amphetamine (ABA); n = 107 6.14 ± 2.17 5.25 ± 2.26 6.80 ± 1.48 intercept ABA / C DRD4 Ex3 ABA / C x DRD4 Ex3 F 1,301 = 844.01 ( p < 0.0001) F 1,301 = 0.92 ( p = 0.3402) F 2,301 = 2.97 ( p = 0.0528) F 2,301 = 0.96 ( p = 0.3838) 0.738 0.003 0.019 0.006 1.000 0.159 0.575 0.216 Control (C); n = 200 5.76 ± 1.98 5.47 ± 2.25 5.80 ± 2.24 *–significant result; CBA- Addiction of behavioral and amphetamine; M ± SD - mean ± standard deviation. Table 5. Post hoc test (Bonferroni) analysis of interactions between the patients diagnosed with Addiction of behavioural and amphetamine /control and rs3864236 and Extraversion scale. DRD4 Ex3 and Extraversion scale {1} M=6.23 {2} M=7.37 {3} M=5.80 {4} M=5.52 {5} M=5.09 {6} M=5.72 Addiction to behavioural and amphetamine s/l {1} 0.0163* 0.6804 0.1302 0.0121* 0.3843 Addiction to behavioral and amphetamine s/s {2} 0.1186 0.0000* 0.0000* 0.0012* Addiction to behavioral and amphetamine l/l {3} 0.7807 0.4770 0.9402 Control s/l {4} 0.1967 0.6909 Control s/s {5} 0.1963 Control l/l {6} DRD4 Ex3 and Neuroticism scale {1} M=5.89 {2} M=6.90 {3} M=5.80 {4} M=4.96 {5} M=4.60 {6} M=4.76 Addiction to behavioural and amphetamine s/l {1} 0.0269* 0.9228 0.0382* 0.0030* 0.0438* Addiction to behavioral and amphetamine s/s {2} 0.2473 0.0000* 0.0000* 0.0000* Addiction to behavioral and amphetamine l/l {3} 0.3773 0.2040 0.3029 Control s/l {4} 0.2528 0.6740 Control s/s {5} 0.7282 Control l/l {6} *–significant result 4. Discussion In behavioural and amphetamine addicts with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more frequently compared to the control group with the s/s polymorphism. Another significant difference worth noting in the post hoc test is that in people addicted to behavioural and amphetamine, with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to people with an addiction. of behavioral and amphetamine with DRD4 Ex3 s/l gene polymorphism. The Neuroticism trait combined with the s/s genotype of the DRD4 gene polymorphism is particularly noteworthy. Of course, when analysing the results obtained, it should be remembered that addiction is a biologically complex entity and a multifactorial disease. Psychological, genetic and environmental factors have a huge impact. But when considering epigenetic research, we must also remember about pharmacotherapy and physiological conditions. Many researchers focus on the analysis of genetic factors, recently analysing individual polymorphic variants in connection with psychological features. The effect of such discoveries may be translated into the development of scientific foundations related to the prevention or treatment of people with an addiction [ 29 ]. The association of dopamine receptor genes [ 44 – 55 ] with novelty seeking [ 32 – 34 ], impulsivity [ 35 , 36 ], risky behaviour [ 30 , 31 ], and attention deficit hyperactivity disorder [ 37 – 41 ] has been demonstrated. Behavioral addiction [ 56 – 60 ], temperament [ 42 , 43 ]. As in our study, the dopamine receptor 4 DRD4 has been studied much earlier as associated with novelty seeking and harm avoidance. Not all studies in this field confirmed this assumption; some were contradictory [ 61 , 62 ]. However, animal studies are crucial to help understand the neurobiological basis of the problem. Regardless of gender, DRD4 knockout mice show significantly reduced exploration of new stimuli used to recognise test objects and were considerably less likely to enter the centre of the arena during the test [ 61 , 63 , 64 ]. Some D4 receptor knockout mice have reduced DOPAC and DA turnover rates in the nucleus accumbens, suggesting that DRD4 expression may play a role in dopamine-related disorders like ADHD [ 65 ]. This DRD4 antagonist has been observed to attenuate nicotine exposure-induced reinstatement of nicotine seeking. This included both drug-related signals and failure to reinstate treatment after nicotine administration [ 66 ]. Similar studies concerned cocaine addiction, which was associated with impaired inhibitory and decision-making control [ 67 , 68 ] and sensation and novelty seeking [ 69 , 70 ], as well as impulsivity and anxiety [ 71 – 73 ]. Since the D4 dopamine receptor gene is associated with human behaviour, it is also likely that it is associated with behaviours aimed at seeking an addictive substance [ 74 ]. Since the polymorphism we analysed is a tandem repeat variable, like other researchers, we divided the alleles into short (s) − 2–6 VNTR and long (l) 7–11 VNTR [ 75 ]. This division is based on the influence on the expression of the DRD4 gene by individual VNTRs [ 76 ], as it is a functional polymorphism [ 77 – 81 ]. Studies have shown that the 7-repeat allele, compared to the 2- and 4-repeat alleles, suppresses the expression of reporter genes in vectors [ 82 ] and also results in reduced RNA stability or translation efficiency and de-creased mRNA levels [ 82 , 83 ]. This suggests that the 7-repeat allele is less functionally active than other VNTRs. Indeed, carrier 7 repeat alleles have explicitly been associated with several reward-related behaviours, including smoking in men diagnosed with ADHD [ 83 ], higher rates of lifelong smoking and lower rates of smoking cessation [ 84 ], and methamphetamine abuse [ 85 ] and general psychoactive sub-stance use [ 86 ] [ 87 ]. Analyzing the work of other researchers, we can notice that not all of them observed differences at the level of statistical significance when analyzing s alleles and l alleles in the group of addicts and in the control group. Analysing the work of other researchers, we can notice that not all observed differences at the level of statistical significance when analysing S alleles and L alleles in the group of people with addiction and the control group [ 88 ]. McGeary J [ 89 ] stated that there was consistent evidence to explain the association of the VNTR L allele with addictive behaviour by the fact that the VNTR-L allele is associated with lower receptor density and reduced sensitivity to dopamine [ 89 ]. The rs1611115 (-1021C > T) allele of the DβH gene reduces enzyme activity [ 90 ], but the evidence for an association of this polymorphism with addictive behaviour is weak [ 91 ]. The dopamine D4 receptor gene has gained considerable attention due to its polymorphic structure and promising reports of an association between the 7-repeat allele and addictive behaviour [ 92 , 93 ], as well as the personality trait of novelty-seeking [ 94 , 95 ]. Novelty-seeking, in turn, is postulated to represent a risk factor for addiction [ 96 ]. When analysing our research results, it isn't easy to refer to the analyses of other researchers. The poly-morphism of the DRD4 gene associated with novelty seeking is often studied in addictions; 7 or more VNTR repeats are associated with novelty seeking and are reasonably described as dopamine reuptake in the synapse. However, our research shed new light on multigene and multifactor analyses that consider psychological factors. There is still too little research on this topic, but this is the right direction. Our study focused solely on individuals of Caucasian descent, necessitating vali-dation of our findings across diverse populations. Furthermore, our analysis concentrated on a single SNP within the DRD4 gene, limiting the scope of our conclusions based on this specific dataset. To augment our understanding, future investigations will encompass methylation analysis across a larger cohort encompassing varied sub-stance addictions, enabling a more comprehensive exploration of the DRD4 gene's role. 5. Conclusions In the presented study, we see that addictions should be analysed multi-factorial. We can conclude that DRD4 and its polymorphic variant influence addiction development. Still, considering its multifactorial and polygenic nature, it should be combined with other factors such as personality. The presented group is also interesting, as it confirms the multithreadedness and combination of behavioural addiction with substance addiction. We hope that these and similar discoveries will translate into clinical practice in the future. There are also limitations to the study. A similar analysis scheme should be carried out on a larger group of subjects and consider a larger number of tested genes. Declarations Author Contributions: “Conceptualisation, AB and AG; methodology, AB; RR, and AG; software KC, RR, validation, JC; formal analysis, KC; investigation, AB, AG; resources, AS-P; data curation, GT; writing—original draft preparation, AB, AG, RR, KC, AS-P, JC, GT, MTK, J.M; writing—review and editing, AG, RR, GT, KC, AS-P, JC, JM, M.G-D.; visualisation, KC; supervision, AG; project administration, AG; funding acquisition, AG. Funding: This research was funded by the National Science Center, Poland, grant number UMO 2015/19/B/NZ7/03691. Institutional Review Board Statement: Approval was obtained from the Bioethical Committee of the Pomeranian Medical University in Szczecin (KB-0012/164/17-A). Conflicts of Interest: The authors declare no conflicts of interest. Data publicly available in a repository: https://data.mendeley.com/preview/fcsc5hr4x7?a=cef08628-c0c8-4286-be3c-06f4d1013fd7 References Blum, K.; Cull, J.G.; Braverman, E.R.; Chen, T.J.H.; Comings, D.E. 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Chen, C.K.; Hu, X.; Lin, S.K.; Sham, P.C.; Loh, E.W.; Li, T.; Murray, R.M.; Ball, D.M. Association Analysis of Dopamine D2-like Receptor Genes and Methamphetamine Abuse. Psychiatr Genet 2004, 14, 223–226, doi:10.1097/00041444-200412000-00011. Skowronek, M.H.; Laucht, M.; Hohm, E.; Becker, K.; Schmidt, M.H. Interaction between the Dopamine D4 Receptor and the Serotonin Transporter Promoter Polymorphisms in Alcohol and Tobacco Use among 15-Year-Olds. Neurogenetics 2006, 7, 239–246, doi:10.1007/S10048-006-0050-4/METRICS. Michaelides, M.; Pascau, J.; Gispert, J.D.; Delis, F.; Grandy, D.K.; Wang, G.J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K. Dopamine D4 Receptors Modulate Brain Metabolic Activity in the Prefrontal Cortex and Cerebellum at Rest and in Response to Methylphenidate. Eur J Neurosci 2010, 32, 668, doi:10.1111/J.1460-9568.2010.07319.X. Lohoff, F.W.; Bloch, P.J.; Hodge, R.; Nall, A.H.; Ferraro, T.N.; Kampman, K.M.; Dackis, C.A.; O’Brien, C.P.; Pettinati, H.M.; Oslin, D.W. Association Analysis between Polymorphisms in the Dopamine D2 Receptor (DRD2) and Dopamine Transporter (DAT1) Genes with Cocaine Dependence. Neurosci Lett 2010, 473, 87–91, doi:10.1016/J.NEULET.2010.02.021. McGeary, J. The DRD4 Exon 3 VNTR Polymorphism and Addiction-Related Phenotypes: A Review. Pharmacol Biochem Behav 2009, 93, 222–229, doi:10.1016/J.PBB.2009.03.010. Kreek, M.J.; Bart, G.; Lilly, C.; Laforge, K.S.; Nielsen, D.A. Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments. Pharmacol Rev 2005, 57, 1–26, doi:10.1124/PR.57.1.1. Guindalini, C.; Laranjeira, R.; Collier, D.; Messas, G.; Vallada, H.; Breen, G. Dopamine-Beta Hydroxylase Polymorphism and Cocaine Addiction. Behav Brain Funct 2008, 4, 1, doi:10.1186/1744-9081-4-1. Kotler, M.; Cohen, H.; Segman, R.; Gritsenko, I.; Nemanov, L.; Lerer, B.; Kramer, I.; Zer-Zion, M.; Kletz, I.; Ebstein, R.P. Excess Dopamine D4 Receptor (D4DR) Exon III Seven Repeat Allele in Opioid-Dependent Subjects. Mol Psychiatry 1997, 2, 251–254, doi:10.1038/SJ.MP.4000248. Li, T.; Xu, K.; Deng, H.; Cai, G.; Liu, J.; Liu, X.; Wang, R.; Xiang, X.; Zhao, J.; Murray, R.M.; et al. Association Analysis of the Dopamine D4 Gene Exon III VNTR and Heroin Abuse in Chinese Subjects. Mol Psychiatry 1997, 2, 413–416, doi:10.1038/SJ.MP.4000310. Ebstein, R.P.; Novick, O.; Umansky, R.; Priel, B.; Osher, Y.; Blaine, D.; Bennett, E.R.; Nemanov, L.; Katz, M.; Belmaker, R.H. Dopamine D4 Receptor (D4DR) Exon III Polymorphism Associated with the Human Personality Trait of Novelty Seeking. Nat Genet 1996, 12, 78–80, doi:10.1038/NG0196-78. Benjamin, J.; Li, L.; Patterson, C.; Greenberg, B.D.; Murphy, D.L.; Hamer, D.H. Population and Familial Association between the D4 Dopamine Receptor Gene and Measures of Novelty Seeking. Nat Genet 1996, 12, 81–84, doi:10.1038/NG0196-81. Adriani, W.; Chiarotti, F.; Laviola, G. Elevated Novelty Seeking and Peculiar D-Amphetamine Sensitization in Periadolescent Mice Compared with Adult Mice. Behavioral neuroscience 1998, 112, 1152–1166, doi:10.1037//0735-7044.112.5.1152. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4409644","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":311412222,"identity":"f7690c61-2e2f-47c1-b796-80670568537d","order_by":0,"name":"Agnieszka Boroń","email":"","orcid":"","institution":"Pomeranian Medical University in Szczecin","correspondingAuthor":false,"prefix":"","firstName":"Agnieszka","middleName":"","lastName":"Boroń","suffix":""},{"id":311412223,"identity":"57640b83-c89d-47eb-aa37-2653d6e28995","order_by":1,"name":"Remigiusz Recław","email":"","orcid":"","institution":"Pomeranian Medical University in Szczecin","correspondingAuthor":false,"prefix":"","firstName":"Remigiusz","middleName":"","lastName":"Recław","suffix":""},{"id":311412224,"identity":"9ff6c8ea-7864-4a02-97b0-1c9a20a4e242","order_by":2,"name":"Krzysztof Chmielowiec","email":"","orcid":"","institution":"University of Zielona Góra","correspondingAuthor":false,"prefix":"","firstName":"Krzysztof","middleName":"","lastName":"Chmielowiec","suffix":""},{"id":311412225,"identity":"f0f90f88-d0f6-4b80-b5fc-28375867193e","order_by":3,"name":"Jolanta Chmielowiec","email":"","orcid":"","institution":"University of Zielona Góra","correspondingAuthor":false,"prefix":"","firstName":"Jolanta","middleName":"","lastName":"Chmielowiec","suffix":""},{"id":311412226,"identity":"8490c744-47b4-4a2f-b848-73e2a95ef9b6","order_by":4,"name":"Aleksandra Strońska-Pluta","email":"","orcid":"","institution":"Pomeranian Medical University in Szczecin","correspondingAuthor":false,"prefix":"","firstName":"Aleksandra","middleName":"","lastName":"Strońska-Pluta","suffix":""},{"id":311412228,"identity":"a6763a85-3110-467e-b30b-a6a91fe5dec0","order_by":5,"name":"Michał Tomasz Kowalski","email":"","orcid":"","institution":"Nowa Sól Multidisciplinary Hospital","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"Tomasz","lastName":"Kowalski","suffix":""},{"id":311412229,"identity":"14373df0-4b2b-4bc0-b0c5-6ede4a0f532d","order_by":6,"name":"Jolanta Masiak","email":"","orcid":"","institution":"Medical University of Lublin","correspondingAuthor":false,"prefix":"","firstName":"Jolanta","middleName":"","lastName":"Masiak","suffix":""},{"id":311412232,"identity":"b27bff35-bb4b-45ff-981d-3c70a3fd30ba","order_by":7,"name":"Magdalena Gibas-Dorna","email":"","orcid":"","institution":"University of Zielona Gora","correspondingAuthor":false,"prefix":"","firstName":"Magdalena","middleName":"","lastName":"Gibas-Dorna","suffix":""},{"id":311412235,"identity":"5c2d6165-c8fe-46d7-a8ee-53d09e41e6d8","order_by":8,"name":"Grzegorz Trybek","email":"","orcid":"","institution":"Pomeranian Medical University in Szczecin","correspondingAuthor":false,"prefix":"","firstName":"Grzegorz","middleName":"","lastName":"Trybek","suffix":""},{"id":311412236,"identity":"e58abf86-6b2d-46e2-8485-775de09cd8f2","order_by":9,"name":"Anna Grzy-wacz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYCgAORBx4AEpWozBWhJI0ZLYACLxaZGPPv5MmqfGzp6B/eyxBz8YtqXPDzv8EGiLnZxuA3YthucS0qR5jiUzM/DkpRv2MNzO3Xg7zQCoJdnY7AAOLT0Mx6Rz2A6wMTDkmEnwgLTMTgBpOZC4DacWxjbpnH8HeBj435hJ/mG4nW44O/0DXi3yPMxs0rltByQYJHLMpIG2JMhL5+C3xYCHjdn6b1+yAZvEGzNpGYPbhhukcwoOJBjg9ot8D/vDmzO+2dnz8+eYSb6puC0vPzt984cPFXZyuLQYHGBgkQAx2CBcsAiEgQvINzAwf0AXGQWjYBSMglGAAgAv5Vd7x9C3/AAAAABJRU5ErkJggg==","orcid":"","institution":"Pomeranian Medical University in Szczecin","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Grzy-wacz","suffix":""}],"badges":[],"createdAt":"2024-05-12 20:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4409644/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4409644/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58154746,"identity":"8f6f9dce-3b3c-4651-8ea4-d3e3c1c26d2f","added_by":"auto","created_at":"2024-06-11 20:41:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11968,"visible":true,"origin":"","legend":"\u003cp\u003eInteraction between Addiction of behavioural and amphetamine (A BS) /control (C) and DRD4 Ex3 and STAI trait scale.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4409644/v1/ae2405ec6c9700ba87f46ba4.png"},{"id":58154745,"identity":"dc7556ea-54d0-41f4-a8fe-35577aa0acb2","added_by":"auto","created_at":"2024-06-11 20:41:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11776,"visible":true,"origin":"","legend":"\u003cp\u003eInteraction between Addiction of behavioural and amphetamine (A BS) /control (C) and DRD4 Ex3 and Neuroticism scale.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4409644/v1/521d85afbfb7b109cf4afb3e.png"},{"id":58362123,"identity":"c9ea7007-5ae9-4e87-ac7e-32b6915e93c9","added_by":"auto","created_at":"2024-06-14 11:35:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":799680,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4409644/v1/48646213-54cb-4d4b-91e0-dccd0938a7b5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association analysis of the Ex3 VNTR polymorphism of the DRD4 dopamine receptor gene with personality traits in patients with a behavioural addiction","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eResearch on the biology and genetics of addiction has been going on for several decades. Despite many analyses, we still do not know a clear answer to the question of which genetic or epigenetic factors are most responsible for the development and course of ad-diction. However, we know that these are multi-gene and multi-factor entities, particularly related to cerebral neurotransmission, and it is justified to analyse these factors simultaneously. To better understand the co-occurrence of addictions and internalising syndromes such as depression, studies examining dopaminergic polymorphisms may be particularly promising. Influential theoretical propositions such as \"reward deficiency syndrome\" [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] suggest that variants of the D2 dopamine-like receptor genes make some individuals less likely to experience rewards from everyday activities, leading to general dysphoria and seeking more significant sensations with sub-stance abuse. Therefore, studies have associated dopaminergic polymorphisms with externalising and internalising syndromes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In the present study, we specifically looked at the polymorphism of the DRD4 dopamine receptor gene, which is widely described in the literature as associated with sensation seeking. This applies to both people who abuse substances and those who suffer from mood disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Substance use disorder (SUD) is also known as drug use disorder, in which the misuse of one or more substances leads to the inability to work to control the use of the drug or medications. SUD is characterised by mental, physical and behavioural impairment [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. SUD is also defined as a multifactorial disorder, de-pending on several causes, such as individual genetic background \u0026minus;\u0026thinsp;40 to 60% of susceptibility to SUD and environmental factors, including peer pressure, emotional anxiety, and depression [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It is important to remember that genes alone do not determine the ad-diction phenotype. Environmental factors also play an important role. In general, the initiation and use of substances during adolescence are largely influenced by common environmental factors, although genetic factors and specific environmental factors also play a role. At later ages and with more rigorous measures of substance use, individual differences between people can only be explained by genetic factors and unique environmental factors. This pattern seems logical because in early adolescence, teenagers tend to have fewer opportunities to express their genetic predispositions because most of their actions and decisions are influenced by people in positions of authority (such as parents). As teenagers move into adulthood and typically leave the social structure of their youth, they have more opportunities to express their genetic predispositions, choosing more freely among friends, activities, and environments [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen considering possible genetic risk factors for SUD, new molecular techniques have been applied to identify candidate genes associated with regulating neurotransmitters and substance metabolism [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. One of the genetic markers is a polymorphic variant in exon III of the dopamine receptor 4 (DRD4) - a variable number tandem repeat (VNTR) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The DRD4 gene is located on chromosome 11, which encodes a 7-transmembrane G-protein-coupled receptor to which endogenous dopamine responds [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A sequence of 48 base pairs with a repeat range of 2\u0026ndash;11 existed. 2, 4 and 7 repeats are considered the most common genotypes that can change receptor sensitivity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The number of repetitions has a functional effect on the dopamine receptor. For example, seven or more repeats correlated with blunted intracellular and dopamine sensitivity [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany biological models can explain substance use, addictive disorders and susceptibility to addiction [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Most models are not mutually exclusive but rather complementary; they investigate various aspects of addictive behaviours, particularly dopaminergic circuits. The mesolimbic dopaminergic system is a neural circuit involving the nucleus accumbens (in the ventral striatum) receiving dopaminergic inputs from the ventral teg-mental area [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This neural circuit is a common reward neural pathway. Do-pa-mine-releasing activity in the nucleus accumbens is associated with reward responsive-ness to both substance-based rewards (e.g., cocaine) and \u0026ldquo;natural\u0026rdquo; rewards (e.g., sex, video games). [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Reward-oriented models of addiction focus on reward processing and the reinforcing aspect of drug use. One model posits that repeated exposure to a drug or appetitive behaviour in susceptible individuals can excite these neural circuits and influence hedonic attitudes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. So, over time, addictive behaviours can \u0026ldquo;take over\u0026rdquo; the natural system rewards in the brain, in effect making it more sensitive to the primary drug and less sensitive to other \"natural\" reinforcers/rewards.\u003c/p\u003e \u003cp\u003eDopamine is not the only important neurotransmitter, nor is the midbrain dopaminergic system the only brain area important in models of addiction. Addictive disorders involve dysfunction in the expression and function of a wide range of neurotransmitters and neuropeptides, including glutamate, gamma-aminobutyric acid (GABA), serotonin, norepinephrine, and acetylcholine, as well as corticotrophin-releasing factor, opioids, cannabinoids, oxytocin, vasopressin, and neuropeptide Y [ 18]. Different areas of the brain have also been associated with different stages of the addiction cycle [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. While the mid-brain dopaminergic system and its associated dorsal striatum appear to be important in cases of abuse and even intoxication, stress-related neurocircuitry systems, including the extended amygdala and the central and peripheral noradrenergic systems, appear to be responsible for processes relevant to states of negative affect. And withdrawal. The basolateral prefrontal cortex, the amygdala, the insula, and the hippocampus are associated with states of hunger [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, when considering the neurobiology of addictions, it is necessary to take the psychological factor into account. Recent research has sorted the psychological components of reward processing into domains, including reward expectation and valuation, reinforcement learning, salience attribution, and loss/punishment processing [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Ber-ridge and Robinson [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] proposed a motivational model of addiction, which suggests that \"liking\" (the affective response of feeling pleasure) and \"wanting\" (stimulus-based motivation) can be separated anatomically and chemically. \u0026ldquo;Reward Deficiency Syn-drome\u0026rdquo; is another reward-oriented model of addiction vulnerability that posits that de-creased responsiveness of the midbrain dopaminergic system may lead individuals at risk for sub-stance dependence and addictive disorders to seek out and engage in addictive behaviours to compensate for insufficient arousal. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The reward deficit model is consistent with drug-based theories of addiction [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Addiction models include elements of motivation, cognitive control, and decision-making. They argue that addictive disorders may represent misdirected motivation in which relatively greater priority is given to appetitive behaviours, such as drug use, and less to other behaviours, such as work, school, and family care [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Thus, the motivation to engage in appetitive be-haviour \"outweighs\" other motivational goals. These models incorporate the neuroeconomic concept of temporal discounting: choosing smaller immediate rewards over larger delayed rewards. These decision-making pathways are associated with distinct brain regions and circuits [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Biologically, the selection of smaller immediate rewards appears to be related to the ventral striatum and ventromedial PFC activity. In contrast, the selection of larger delayed rewards appears to be associated with dorsal prefrontal areas, although the subjective value of immediate or delayed reward may influence the neural response [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Since the described factors are related, the present study concerns the analysis of the genetic factor in connection with the psychological factor related to personality.\u003c/p\u003e \u003cp\u003eIt is known that gambling addiction and substance addiction share similar biological mechanisms and symptoms, therefore our goal in this work is to analyze the DRD4 Ex3 s/s gene polymorphism in patients addicted to gambling and substances compared to healthy controls. The study also assessed personality measured using the NEO-FFI questionnaire and anxiety measured using the STAI questionnaire in all study groups.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Participants\u003c/h2\u003e \u003cp\u003eThe study group consisted of 307 volunteers. Of these, 107 addiction behavioural and amphetamine men with three months of abstinence staying in addiction treatment units (mean age\u0026thinsp;=\u0026thinsp;27.51, SD\u0026thinsp;=\u0026thinsp;5.25;) and 200 men who were not addicted and had no mental disorders (mean age\u0026thinsp;=\u0026thinsp;20.20, SD\u0026thinsp;=\u0026thinsp;4.51;). Addicted people were recruited to addiction treatment centers in the Lubusz Voivodeship. Both groups were examined by the psychia-trist using the Mini-International Neuropsychiatric Interview (M.I.N.I). People with psychotic symptoms and mental disorders other than behavioral and amphetamine addiction were excluded from the study. None of the addicted people received pharmacothera-py. The control group consisted of healthy, non-addicted people without mental disorders and not practicing competitive sports. Both addiction behavioural and amphetamine and the control group undergo the same psychometric testing with the NEO Five-Factor Personality Inventory (NEO-FFI) and State-Trait Anxiety Inventory (STAI) questionnaire.\u003c/p\u003e \u003cp\u003e The Bioethics Committee of the Pomeranian Medical University in Szczecin approved the study (KB-0012/164/17-A). All participants gave their written, informed consent before entering the study. All methods were performed in accordance with the relevant guidelines and regulations. Research was performed in accordance with the Declaration of Helsinki. The study was conducted in the Independent Health Promotion Laboratory, Pomeranian Medical University in Szczecin.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Psychometric tests\u003c/h2\u003e \u003cp\u003eSTAI questionnaire measures anxiety as a trait, which can be described as a persistent predisposition to having worries, stress, and discomfort, and anxiety as a state, which can be described as anxiety, fear, and momentary stimulation of the autonomic nervous sys-tem in response to specific situations.\u003c/p\u003e \u003cp\u003eThe Personality Inventory (NEO-FFI Five-Factor Inventory, NEO-FFI) contains six components for each of the five traits - neuroticism (anxiety, hostility, depression, self-awareness, impulsivity, susceptibility to stress), extroversion (warmth, sociability, assertiveness, activity, emotion seeking, positive emotions), openness to experience (fantasy, aesthetics, feelings, actions, ideas, values), agreeableness (trust, straightforwardness, al-truism, compliance, modesty, tenderness), conscientiousness (competence, order, duty, striving for achievements, self-discipline, consideration).\u003c/p\u003e \u003cp\u003eThe results of both inventories, i.e., NEO-FFI and STAI., were reported as the sten scores. The conversion of the raw score to the sten scale was carried out following the Polish standards for adults, where it was assumed that 1\u0026ndash;2 sten corresponds to very low results, 3\u0026ndash;4 low results, 5\u0026ndash;6 average results, 7\u0026ndash;8 high results, and 9\u0026ndash;10 sten corresponds to very high results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Genotyping\u003c/h2\u003e \u003cp\u003eThe genomic DNA was isolated from venous blood by using standard procedures. Geno-typing was conducted with the real-time PCR method. Link to data placed in the repository:\u003c/p\u003e \u003cp\u003e \u003cspan class=\"ExternalRef\"\u003e \u003cspan class=\"RefSource\"\u003ehttps://data.mendeley.com/preview/fcsc5hr4x7?a=cef08628-c0c8-4286-be3c-06f4d1013fd7\u003c/span\u003e \u003cspan address=\"https://data.mendeley.com/preview/fcsc5hr4x7?a=cef08628-c0c8-4286-be3c-06f4d1013fd7\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e \u003c/span\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical Analysis\u003c/h2\u003e \u003cp\u003eA concordance between the genotype frequency distribution and Hardy-Weinberg equilibrium (HWE) was tested using the HWE software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://wpcalc.com/en/equilibrium-hardy-weinberg/\u003c/span\u003e\u003cspan address=\"https://wpcalc.com/en/equilibrium-hardy-weinberg/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (03 December 2023). The relations between DRD4 Ex3 variants: addiction of behavioural and amphetamine and control subjects and the NEO Five-Factor Inventory were analysed using a multivariate analysis of factor effects ANOVA [NEO-FFI/ scale STAI/ \u0026times; genetic feature \u0026times; control and addiction of behavioural and amphetamine \u0026times; (genetic feature \u0026times; control and addiction of behavioural and amphetamine)]. The condition of homogeneity of variance was fulfilled (Levene test p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The analysed variables were not distributed normally. The NEO Five-Factor Inventory (Neuroticism, Extraversion, Openness, Agreeability, and Conscientiousness) sten scores were compared using the U Mann\u0026ndash;Whitney test DRD4 Ex3 genotype frequencies between control subjects and addiction of behavioural and amphetamine were tested using the chi-square test. All computations were performed using STATISTICA 13 (Tibco Software Inc, Palo Alto, CA, USA) for Windows (Microsoft Corporation, Redmond, WA, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eThese frequency distributions for the DRD4 Ex3 gene accorded with the Hardy-Weinberg equilibrium (HWE) both in the addiction of behavioural and amphetamine and control subjects. In the addiction of behavioral and amphetamine subjects, homozygote reference s/s constituted 72 observations and calculated expected 70.7, heterozygote s/l constituted 30 observations and calculated expected 32.5 and homozygote variant l/l constituted 5 observations and calculated expected 3.7 (\u0026chi;2\u0026thinsp;=\u0026thinsp;0.644; p\u0026thinsp;=\u0026thinsp;0.4222). In the control group, it was found that homozygote reference s/s constituted 100 observations and calculated expected 94.5, heterozygote s/l constituted 75 observations and calculated ex-pected 85.9 and homozygote variant l/l constituted 25 observations and calculated expected 19.5. (\u0026chi;2\u0026thinsp;=\u0026thinsp;3.239; p\u0026thinsp;=\u0026thinsp;0.0719, Table \u003cspan\u003e1\u003c/span\u003e.).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eHardy-Weinberg\u0026apos;s equilibrium for the \u003cem\u003eDRD4 Ex3\u003c/em\u003e gene.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHardy-Weinberg equilibrium calculator, including analysis for ascertainment bias\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eObserved (Expected)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eallele freq\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003ep-value\u003c/em\u003e)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eDRD4 Ex3 Addiction to behavioral and amphetamine\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003ep (s)\u0026thinsp;=\u0026thinsp;0.81\u003c/p\u003e\n \u003cp\u003eq (ll)\u0026thinsp;=\u0026thinsp;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0.644\u003c/p\u003e\n \u003cp\u003e(0.4222)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72 (70.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003el/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eDRD4 Ex3 control\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75 (85.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003ep (s)\u0026thinsp;=\u0026thinsp;0.69\u003c/p\u003e\n \u003cp\u003eq (l)\u0026thinsp;=\u0026thinsp;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e3.239\u003c/p\u003e\n \u003cp\u003e(0.0719)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100 (94.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003el/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003ep\u0026ndash;\u003c/em\u003estatistical significance \u0026chi;\u003csup\u003e2\u003c/sup\u003e test.\u003c/p\u003e\n\u003cp\u003eStatistically significant differences were found in the frequency of DRD4 Ex3 genotypes in the tested sample of Addiction of behavioural and amphetamine when compared to the control group. In the subjects, the addiction of behavioral and amphetamine homozygote reference s/s constituted a higher percentage compared to the control group, while a lower percentage was found for hetozygote s/l and for homozygote variant l/l (s / l 0.28 vs s / l 0.37; s / s 0.67 vs s / s 0.50; l / l 0.05 vs l / l 0.12, \u0026chi;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;9.914, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0070).\u003c/p\u003e\n\u003cp\u003eStatistically significant differences in the frequency of rs3864236 alleles were found between Addiction of behavioural and amphetamine and the control group. In the addiction of behavioral and amphetamine subjects, the s allele occurred more often compared to the control group, while the l allele occurred less frequently. (s 0.81 vs s 0.69; l 0.19 vs l 0.31, \u0026chi;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;11.190, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0008) (Table \u003cspan\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1717763434.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n\u003cp\u003eThe means and standard deviations of the NEO-FFI results and the STAI state and trait scale for the Addiction of behavioural and amphetamine and control subjects are shown in Table \u003cspan\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eSTAI and NEO Five-Factor Inventory sten scores between healthy controls and Addiction of behavioural and amphetamine.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSTAI/ NEO Five-Factor Inventory/\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;371)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;151)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(p-Value)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSTAI trait/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.98\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0019*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSTAI state/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.575\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0000*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeuroticism/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.58\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0000*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtraversion/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.99\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.28\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2529\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOpenness/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.765\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4442\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAgreeability/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0000*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConscientiousness/scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.57\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003ep\u003c/em\u003e, statistical significance with Mann\u0026ndash;Whitney U-test; \u003cem\u003en\u003c/em\u003e, number of subjects; M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; * statistically significant differences.\u003c/p\u003e\n\u003cp\u003eThe Addiction of behavioural and amphetamine compared to the control group obtained higher scores in the assessment of the STAI trait scale (6.98 vs 5.33; Z\u0026thinsp;=\u0026thinsp;3.106; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0019), of STAI state scale (5.60 vs 4.77; Z\u0026thinsp;=\u0026thinsp;5.575; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0000) and NEO-FFI neuroticism scale (6.58 vs 4.76; Z\u0026thinsp;=\u0026thinsp;36.657; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0000). Significantly lower results were obtained for the NEO-FFI agreeability scale (4.28 vs 5.54; Z = -4.941; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0000).\u003c/p\u003e\n\u003cp\u003eThe results of the factorial ANOVA of the STAI trait and state the NEO Five-Factor Personality Inventory, and the State-Trait Anxiety Inventory sten scales are summarised in Table \u003cspan\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eSignificant statistical impact of Addiction of behavioural and amphetamine and DRD4 Ex3 genotype was demonstrated for a score of the STAI trait scale.\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant effect of DRD4 Ex3 genotype interaction and Addiction of behavioural and amphetamine or not using (control group) on the STAI trait scale (F\u003csub\u003e2.301\u003c/sub\u003e = 4.85; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0084; \u0026eta;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.031; Fig. \u003cspan\u003e1\u003c/span\u003e.). The power observed for this factor was 80%, and approximately 3% was explained by the polymorphism of the DRD4 Ex3 and Addiction of behavioural and amphetamine or lack thereof on trait extraversion score variance. There was also a statistically significant effect of Addiction to behavioural and amphetamine or the control group on the STAI trait scale score (F\u003csub\u003e1.301\u003c/sub\u003e = 6.44; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0116; \u0026eta;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.021). The power observed for this factor was over 72%, and approximately 2% was explained by Addiction to behavioural and amphetamine or lack thereof on the variance in the extraversion score. Table \u003cspan\u003e5\u003c/span\u003e shows the results of the post hoc test. In behavioural and amphetamine addicts with a higher level of the STAI trait scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in behavioural and amphetamine addicts with a higher level of the STAI trait scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism. Another significant difference worth noting in the post hoc test is that in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to people addicted to behavioural and amphetamine with the polymorphism. DRD4 Ex3 s/l gene. Significant statistical impact of Addiction of behavioural and amphetamine and DRD4 Ex3 genotype was demonstrated for a score of the NEO-FFI Neuroticism scale.\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant effect of DRD4 Ex3 genotype interaction and of behavioural and amphetamine or not using (control group) on the Neuroticism scale (F\u003csub\u003e2.301\u003c/sub\u003e = 3.38; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0354; \u0026eta;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.022; Fig. \u003cspan\u003e2\u003c/span\u003e.). The power observed for this factor was 63%, and approximately 2% was explained by the polymorphism of the DRD4 Ex3 and Addiction of behavioural and amphetamine or lack thereof on trait Neuroticism score variance. There was also a statistically significant effect of Addiction to behavioral and amphetamine or the control group on the Neuroticism scale score (F\u003csub\u003e1.301\u003c/sub\u003e = 13.89; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002; \u0026eta;\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.044). The power observed for this factor was over 96%, and approximately 4% was explained by Addiction to behavioural and amphetamine or lack thereof on the variance in the Neuroticism score. Table \u003cspan\u003e5\u003c/span\u003e shows the results of the post hoc test. In behavioural and amphetamine addicts with a higher level of the Neuroticism scale trait, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in behavioural and amphetamine addicts with a higher level of the Neuroticism scale trait, the DRD4 Ex3 s/l gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Noteworthy in the post hoc test is an-other marked significant difference in people addicted to behavioural and amphetamine with a higher level of the Neuroticism Scale trait; the DRD4 Ex3 gene polymorphism s/s occurred significantly more often compared to people addicted to behavioural and amphetamine with polymorphism of the DRD4 gene Ex3 s/l.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eThe results of 2 \u0026times; 3 factorial ANOVA for addiction of behavioural and amphetamine and controls, NEO Five-Factor Inventory, STAI and HINT1 rs3864236.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSTAI /NEO Five-Factor Inventory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eANOVA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/l\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;105\u003c/p\u003e\n \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003es/s\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;172\u003c/p\u003e\n \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003el/l\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e\n \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF (p-value)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eɳ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePower (alfa\u0026thinsp;=\u0026thinsp;0,05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSTAI trait scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 868.72 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 6.44 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0116)*\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.96 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3829)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2,301\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e= 4.85 (\u003c/strong\u003e\u003cstrong\u003ep\u003c/strong\u003e\u0026thinsp;\u003cstrong\u003e=\u0026thinsp;0.0084)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.716\u003c/p\u003e\n \u003cp\u003e0.217\u003c/p\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSTAI state scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 566.89 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 0.50 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.4784)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.10 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.9060)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 2.95 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0536)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.653\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003cp\u003e0.573\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eNeuroticism scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.90\u0026thinsp;\u0026plusmn;\u0026thinsp;2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA /C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 821.74 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 13.89 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002)*\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.93 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3946)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2,301\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e= 3.38 (\u003c/strong\u003e\u003cstrong\u003ep\u003c/strong\u003e\u0026thinsp;\u003cstrong\u003e=\u0026thinsp;0.0354)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.960\u003c/p\u003e\n \u003cp\u003e0.211\u003c/p\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eExtraversion scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 1139.03 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 0.51 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.4769)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 2.16 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1174)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 2.11 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1233)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003cp\u003e0.440\u003c/p\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eOpenness scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 809.29 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 0.34 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.5584)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.23 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.7963)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.04 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.9637)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.729\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e0.0002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eAgreeability scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 654.27 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 19.21 (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.0001)*\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 1.61 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.2009)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 1.49 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.2265)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.686\u003c/p\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003cp\u003e0.340\u003c/p\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eConscientiousness scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAddiction to behavioral and amphetamine (ABA); n\u0026thinsp;=\u0026thinsp;107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eintercept\u003c/p\u003e\n \u003cp\u003eABA / C\u003c/p\u003e\n \u003cp\u003eDRD4 Ex3\u003c/p\u003e\n \u003cp\u003eABA / C x DRD4 Ex3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 844.01 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e1,301\u003c/sub\u003e = 0.92 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3402)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 2.97 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0528)\u003c/p\u003e\n \u003cp\u003eF\u003csub\u003e2,301\u003c/sub\u003e = 0.96 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3838)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.159\u003c/p\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl (C); n\u0026thinsp;=\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*\u0026ndash;significant result; CBA- Addiction of behavioral and amphetamine; M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD - mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan\u003eTable 5.\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003ePost hoc test (Bonferroni) analysis of interactions between the patients diagnosed with Addiction of behavioural and amphetamine /control and \u003cem\u003ers3864236\u0026nbsp;\u003c/em\u003eand Extraversion scale.\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\n \u003cp\u003e\u003cspan\u003eDRD4 Ex3 and Extraversion scale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{1}\u003cbr\u003e\u0026nbsp;M=6.23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{2}\u003cbr\u003e\u0026nbsp;M=7.37\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{3}\u003cbr\u003e\u0026nbsp;M=5.80\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{4}\u003cbr\u003e\u0026nbsp;M=5.52\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{5}\u003cbr\u003e\u0026nbsp;M=5.09\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{6}\u003cbr\u003e\u0026nbsp;M=5.72\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioural and amphetamine s/l {1}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0163*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.6804\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.1302\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0121*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.3843\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioral and amphetamine s/s {2}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.1186\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0000*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0000*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0012*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioral and amphetamine l/l {3}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.7807\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.4770\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.9402\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl s/l {4}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.1967\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.6909\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl s/s {5}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.1963\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl l/l {6}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\n \u003cp\u003e\u003cspan\u003eDRD4 Ex3 and Neuroticism scale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{1}\u003cbr\u003e\u0026nbsp;M=5.89\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{2}\u003cbr\u003e\u0026nbsp;M=6.90\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{3}\u003cbr\u003e\u0026nbsp;M=5.80\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{4}\u003cbr\u003e\u0026nbsp;M=4.96\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{5}\u003cbr\u003e\u0026nbsp;M=4.60\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e{6}\u003cbr\u003e\u0026nbsp;M=4.76\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioural and amphetamine s/l {1}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0269*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.9228\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0382*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0030*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0438*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioral and amphetamine s/s {2}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.2473\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0000*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0000*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.0000*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eAddiction to behavioral and amphetamine l/l {3}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.3773\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.2040\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.3029\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl s/l {4}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.2528\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.6740\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl s/s {5}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e0.7282\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003eControl l/l {6}\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cspan\u003e*\u0026ndash;significant result\u003c/span\u003e\u003c/p\u003e\n\u003cdiv\u003e\u0026nbsp;\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn behavioural and amphetamine addicts with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more frequently compared to the control group with the s/s polymorphism. Another significant difference worth noting in the post hoc test is that in people addicted to behavioural and amphetamine, with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to people with an addiction. of behavioral and amphetamine with DRD4 Ex3 s/l gene polymorphism. The Neuroticism trait combined with the s/s genotype of the DRD4 gene polymorphism is particularly noteworthy. Of course, when analysing the results obtained, it should be remembered that addiction is a biologically complex entity and a multifactorial disease. Psychological, genetic and environmental factors have a huge impact. But when considering epigenetic research, we must also remember about pharmacotherapy and physiological conditions. Many researchers focus on the analysis of genetic factors, recently analysing individual polymorphic variants in connection with psychological features. The effect of such discoveries may be translated into the development of scientific foundations related to the prevention or treatment of people with an addiction [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The association of dopamine receptor genes [\u003cspan additionalcitationids=\"CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53 CR54\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e] with novelty seeking [\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], impulsivity [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], risky behaviour [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], and attention deficit hyperactivity disorder [\u003cspan additionalcitationids=\"CR38 CR39 CR40\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] has been demonstrated. Behavioral addiction [\u003cspan additionalcitationids=\"CR57 CR58 CR59\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e], temperament [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs in our study, the dopamine receptor 4 DRD4 has been studied much earlier as associated with novelty seeking and harm avoidance. Not all studies in this field confirmed this assumption; some were contradictory [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, animal studies are crucial to help understand the neurobiological basis of the problem. Regardless of gender, DRD4 knockout mice show significantly reduced exploration of new stimuli used to recognise test objects and were considerably less likely to enter the centre of the arena during the test [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. Some D4 receptor knockout mice have reduced DOPAC and DA turnover rates in the nucleus accumbens, suggesting that DRD4 expression may play a role in dopamine-related disorders like ADHD [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. This DRD4 antagonist has been observed to attenuate nicotine exposure-induced reinstatement of nicotine seeking. This included both drug-related signals and failure to reinstate treatment after nicotine administration [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. Similar studies concerned cocaine addiction, which was associated with impaired inhibitory and decision-making control [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e] and sensation and novelty seeking [\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e, \u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e], as well as impulsivity and anxiety [\u003cspan additionalcitationids=\"CR72\" citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e]. Since the D4 dopamine receptor gene is associated with human behaviour, it is also likely that it is associated with behaviours aimed at seeking an addictive substance [\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince the polymorphism we analysed is a tandem repeat variable, like other researchers, we divided the alleles into short (s) \u0026minus;\u0026thinsp;2\u0026ndash;6 VNTR and long (l) 7\u0026ndash;11 VNTR [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]. This division is based on the influence on the expression of the DRD4 gene by individual VNTRs [\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e], as it is a functional polymorphism [\u003cspan additionalcitationids=\"CR78 CR79 CR80\" citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e]. Studies have shown that the 7-repeat allele, compared to the 2- and 4-repeat alleles, suppresses the expression of reporter genes in vectors [\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e] and also results in reduced RNA stability or translation efficiency and de-creased mRNA levels [\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e, \u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e]. This suggests that the 7-repeat allele is less functionally active than other VNTRs. Indeed, carrier 7 repeat alleles have explicitly been associated with several reward-related behaviours, including smoking in men diagnosed with ADHD [\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e], higher rates of lifelong smoking and lower rates of smoking cessation [\u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e], and methamphetamine abuse [\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e] and general psychoactive sub-stance use [\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e] [\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnalyzing the work of other researchers, we can notice that not all of them observed differences at the level of statistical significance when analyzing s alleles and l alleles in the group of addicts and in the control group. Analysing the work of other researchers, we can notice that not all observed differences at the level of statistical significance when analysing S alleles and L alleles in the group of people with addiction and the control group [\u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e88\u003c/span\u003e]. McGeary J [\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e] stated that there was consistent evidence to explain the association of the VNTR L allele with addictive behaviour by the fact that the VNTR-L allele is associated with lower receptor density and reduced sensitivity to dopamine [\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e]. The rs1611115 (-1021C\u0026thinsp;\u0026gt;\u0026thinsp;T) allele of the DβH gene reduces enzyme activity [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e], but the evidence for an association of this polymorphism with addictive behaviour is weak [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe dopamine D4 receptor gene has gained considerable attention due to its polymorphic structure and promising reports of an association between the 7-repeat allele and addictive behaviour [\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e, \u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e], as well as the personality trait of novelty-seeking [\u003cspan citationid=\"CR94\" class=\"CitationRef\"\u003e94\u003c/span\u003e, \u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e]. Novelty-seeking, in turn, is postulated to represent a risk factor for addiction [\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen analysing our research results, it isn't easy to refer to the analyses of other researchers. The poly-morphism of the DRD4 gene associated with novelty seeking is often studied in addictions; 7 or more VNTR repeats are associated with novelty seeking and are reasonably described as dopamine reuptake in the synapse. However, our research shed new light on multigene and multifactor analyses that consider psychological factors. There is still too little research on this topic, but this is the right direction.\u003c/p\u003e \u003cp\u003eOur study focused solely on individuals of Caucasian descent, necessitating vali-dation of our findings across diverse populations. Furthermore, our analysis concentrated on a single SNP within the DRD4 gene, limiting the scope of our conclusions based on this specific dataset. To augment our understanding, future investigations will encompass methylation analysis across a larger cohort encompassing varied sub-stance addictions, enabling a more comprehensive exploration of the DRD4 gene's role.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn the presented study, we see that addictions should be analysed multi-factorial. We can conclude that DRD4 and its polymorphic variant influence addiction development. Still, considering its multifactorial and polygenic nature, it should be combined with other factors such as personality. The presented group is also interesting, as it confirms the multithreadedness and combination of behavioural addiction with substance addiction. We hope that these and similar discoveries will translate into clinical practice in the future. There are also limitations to the study. A similar analysis scheme should be carried out on a larger group of subjects and consider a larger number of tested genes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e \u0026ldquo;Conceptualisation, AB and AG; methodology, AB; RR, and AG; software KC, RR, validation, JC; formal analysis, KC; investigation, AB, AG; resources, AS-P; data curation, GT; writing\u0026mdash;original draft preparation, AB, AG, RR, KC, AS-P, JC, GT, MTK, J.M; writing\u0026mdash;review and editing, AG, RR, GT, KC, AS-P, JC, JM, M.G-D.; visualisation, KC; supervision, AG; project administration, AG; funding acquisition, AG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research was funded by the National Science Center, Poland, grant number UMO 2015/19/B/NZ7/03691.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u0026nbsp;\u003c/strong\u003eApproval was obtained from the Bioethical Committee of the Pomeranian Medical University in Szczecin (KB-0012/164/17-A).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData publicly available in a repository:\u003c/strong\u003e https://data.mendeley.com/preview/fcsc5hr4x7?a=cef08628-c0c8-4286-be3c-06f4d1013fd7\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBlum, K.; Cull, J.G.; Braverman, E.R.; Chen, T.J.H.; Comings, D.E. 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Behavioral neuroscience 1998, 112, 1152\u0026ndash;1166, doi:10.1037//0735-7044.112.5.1152.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"behavioral addiction, personality traits, DRD4 gene","lastPublishedDoi":"10.21203/rs.3.rs-4409644/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4409644/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn behavioural and amphetamine addicts with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/s gene polymorphism occurred significantly more often compared to the control group with the s/s polymorphism and the l/l and s/l polymorphism. Similarly, in people addicted to behavioural and amphetamine with a higher level of the STAI trait scale and a higher level of the Neuroticism scale, the DRD4 Ex3 s/l gene polymorphism occurred significantly more frequently compared to the control group with the s/s polymorphism. Conclusions: In the presented study, we see that ad-dictions should be analysed multifactorial. We can conclude that DRD4 and its polymorphic variant influence addiction development.\u003c/p\u003e","manuscriptTitle":"Association analysis of the Ex3 VNTR polymorphism of the DRD4 dopamine receptor gene with personality traits in patients with a behavioural addiction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-11 20:41:10","doi":"10.21203/rs.3.rs-4409644/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9e69c759-91f3-4d23-b33a-cd1f52451829","owner":[],"postedDate":"June 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-14T11:27:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-11 20:41:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4409644","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4409644","identity":"rs-4409644","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}