D.H. Han

Effect of genetic polymorphisms on smoking cessation: a trial of bupropion in Korean male smokers

Background Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome. Objectives The aim of this study is to elucidate the question of whether the abstinence rates by bupropion trial would be different depending on the genotypes. Methods Six candidate genes, thought to be involved in the interaction of nicotine and bupropion (for example, the dopamine receptor type 2, dopamine transporter, norepinephrine transporter, serotonin transporter, catecholamine-O-methyltransferase), and the clinical outcomes of smoking behavior were investigated. The participants were 225 male smokers to whom 150 mg of bupropion SR was administered for 4 weeks. The abstinence rates of specific genotypes were also compared. Main results The results are as follows: (a) the frequencies of the A1/A2 genotype of the dopamine receptor type 2 TaqI A gene and SLC6A3-9 genotype of the dopamine transporter 1 gene were higher in the nonabstinence group than in the abstinence group (χ2=20.40, P<0.01 for A1/A2, χ2=7.76, P=0.01 for SLC6A3-9). The frequencies of the COMTH/COMTH and A/G genotypes of the norepinephrine transporter gene were higher in the abstinence group than in the nonabstinence group (χ2=8.12,P=0.02 for COMTH/COMTH, χ2=3.04, P<0.01 for A/G). (b) Participants having specific genotypes such as homozygotes (A1/A1 or A2/A2) of DRD2 TaqI A, COMTH/COMTH, AG of NET-8, and LL of 5-HTTLPR showed a higher abstinence rate than the other participants. Conclusions It can be concluded that genetic diversity might determine the effects of bupropion on smoking cessation.

Clinical Manifestation of Alcohol Withdrawal Symptoms Related to Genetic Polymorphisms of Two Serotonin Receptors and Serotonin Transporter

Aim: The purpose of this study was to investigate the role of serotonergic genes in the development of alcohol dependence. The manifestation of alcohol withdrawal symptoms related to serotonergic polymorphisms in alcoholics was also examined. Methods: The role of polymorphisms in the serotonin receptor 1A (5-HT1A), serotonin receptor 2A (5-HT2A), and the serotonin transporter gene (5-HTT) promotor region (5-HTTLPR) in the manifestation of individual alcohol withdrawal symptoms was investigated in 97 Korean male inpatients with alcohol dependence and 76 Korean healthy male subjects. The patient’s alcohol withdrawal symptoms were assessed with the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. Results: In the 5-HT1A receptor, the frequency of G– genotype (CC) was significantly higher in patients with alcohol dependence than in normal controls (χ2 = 5.03, p = 0.025). The CIWA-Ar subscale scores of nausea, anxiety, and headache, and total CIWA-Ar scale scores were significantly higher in G+ genotypes (CG+ GG) than in G– genotype (p = 0.005, p = 0.004, p = 0.008, and p = 0.008, respectively). Conclusion: The results suggest that the genetic polymorphism of the 5-HT1A receptor may play a role in alcohol dependence and polymorphisms of serotonergic genes may be important in withdrawal symptoms of patients with alcohol dependence.

The utility of quantitative electroencephalography and Integrated Visual and Auditory Continuous Performance Test as auxiliary tools for the Attention Deficit Hyperactivity Disorder diagnosis

OBJECTIVE This study investigated the clinical utility of quantitative electroencephalography (QEEG) and the Integrated Visual and Auditory Continuous Performance Test (IVA+CPT) as auxiliary tools for assessing Attention Deficit Hyperactivity Disorder (ADHD). METHODS All of 157 subjects were assessed using the Korean version of the Diagnostic Interview Schedule for Children Version IV (DISC-IV). We measured EGG absolute power in 21 channels and conducted IVA+CPT. We analyzed QEEG according to the Hz range: delta (1-4Hz), theta (4-8Hz), slow alpha (8-10Hz), fast alpha (10-13.5Hz), and beta (13.5-30Hz). To remove artifacts, independent component analysis was conducted (ICA), and the tester confirmed the results again. RESULTS All of the IVA+CPT quotients showed significant differences between the ADHD and control groups. The ADHD group showed significantly increased delta and theta activity compared with the control group. The z-scores of theta were negatively correlated with the scores of IVA+CPT in ADHD combined type, and those of beta were positively correlated. CONCLUSIONS IVA+CPT and QEEG significantly discriminated between ADHD and control groups. The commission error of IVA+CPT showed an accuracy of 82.1%, and the omission error of IVA+CPT showed an accuracy of 78.6%. SIGNIFICANCE The IVA+CPT and QEEG are expected to be valuable tools for aiding ADHD diagnosis accurately.

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/ hyperactivity disorder

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Emotionality’ and ‘Over-focus/euphoria’ factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Proneness to crying’ and ‘Nail biting’ item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.