Alkol Bağımlılarında Nitrik Oksit Sentaz-1 (Nos1) Ekzon 1F-Vntr Gen Polimorfizmi'nin Bağımlılık ile İlişkili Özellikler, Kişilik Özellikleri ve Dikkat Eksikliği Hiperaktivite Bozukluğu Belirtileri Üzerine Etkisi
Abstract
Introduction: Studies on the genetic etiology of alcohol addiction and subtypes of addiction syndrome have been focusing on the neurotransmitter systems such as dopamine, serotonin, GABA and glutamate. Furthermore, genes that encode enzymes responsible for alcohol metabolism such as alcohol dehydrogenase, aldehyde dehydrogenase were also being investigated. It is a widely known that attention deficit hyperactivity disorder (ADHD) patients has an increased probability rates for alcohol abuse and also alcohol-substance addiction patients has higher prevalence of ADHD. These findings give rise to the thought that a common etiology could play a role in ADHD and alcohol addiction. Recent studies showed that nitric oxide (NO) system might be an important target to search for the clinical and genetic relationships between ADHD, impulsivity and alcohol dependency. It has been demonstrated that NOS1 exon 1f-VNTR polimorphism had association with ADHD and impulsivity. According to these findings it can be considered that NOS1 exon 1f-VNTR polimorphism could also have association with alcohol addiction. Objectives: In this study, it was aimed to compare alcohol addicted patients and healthy subjects in terms of NOS1 Ex1f-VNTR gene polymorphism; investigating this polymorphism in terms of alcohol consumption parameters. Through these associations, it was also investigated that, whether this polymorphism had an important role on determining the subtypes of alcohol addiction. Furthermore, the association between NOS1 exon 1f-VNTR gene polymorphism and impulsivity and ADHD symptoms was aimed to be investigated. Method: The participants of this study was constituted from the patients who applied to Hacettepe University Department of Psychiatry and Ankara Alcohol and Drug, Research, Treatment and Education Center. Addiction group was composed of 153 alcohol addiction patients. Control group was composed of 129 healthy volunteers who did not receive any psychiatric treatment previously. Firstly, participants were interviewed in clinical setting and their sociodemographic data and alcohol consumption features were investigated. Then, all subjects were evaluated with Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I) and Structured Clinical Interview for DSM-III-R Axis II Disorders (SCID-II). Additionally, all study subjects performed Michigan Alcoholism Screening Test (MAST), Temperament and Character Inventory (TCI), Barratt Impulsiveness Scale-11, UPPS Impulsive Behavior Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. Family History-Research Diagnosis Criteria was examined for investigating the presence of a positive family history for alcohol addiction. The genetic analysis was held through the QF-PCR fragment analysis protocols in University of Hacettepe, Department of Medical Genetics. Results: In this study alcohol addiction patients (AA) were compared with the control group and no significant difference was observed regarding to NOS1 exon 1f-VNTR genotype distribution between the groups. We did not observe any significant difference between the NOS1 exon 1f-VNTR genotype distribution and ADHD symptoms, impulsivity level, alcohol consumption parameters. Temperament and Character Inventory results revealed that sensation seeking, harm avoidence and self-transcendence scores were significantly higher in the AA group; self-directedness, cooperativeness, reward dependence and persistance scores was significantly lower in the the control subjects. In AA group; borderline, antisocial, narcissistic and passive-agressive personality disorder rates were higher. When AA subtypes was determined according to the parameters of the age of alcoholism onset and presence of a family history; we have found that early onset and positive family history groups were associated with more severe alcohol addiction, higher impulsivity and ADHD scores. Conclusion: We did not observe any correlation between NOS1 exon 1f-VNTR genotype distribution and AA, subtypes of AA, ADHD and impulsivity in this study. However, various findings obtained from this study showed that AA, ADHD and impulsivity had clinically associated. Furthermore, it was observed that ADHD symptoms and impulsivity scores was associated with the subtypes of AA.