Development of a Modified Korean Version of the Epworth Sleepiness Scale Reflecting Korean Sociocultural Lifestyle

OBJECTIVE: The Epworth Sleepiness Scale is a measure used for the diagnosis of sleep disorders including obstructive sleep apnea (OSA) syndrome, insomnia, and narcolepsy. Although a Korean version has been developed (the KESS), Korean lifestyle such as the floor culture and low driving rates has not been considered. We aim to develop and validate a modified KESS (mKESS) that reflects the Korean lifestyle. METHODS: The sample consisted of 795 healthy participants and 323 OSA patients. The mKESS was developed by modifying several questions to concern the floor culture (questions 1, 2, 6, and 7) and low driving rates (question 8). Feasibility of the modification was tested by comparing the KESS and mKESS using paired samples t-test and by examining internal consistency reliability. Then, mKESS scores of the OSA patients and general participants were compared to test its validity. RESULTS: Questions 1, 2, 7, and 8 were significantly different when comparing the performances of the general population on both scales. Especially, the mean scores on question 8 were significantly different in the non-driver group, but not in the driver group. Cronbach’s alpha of the mKESS was relatively higher than that of the KESS. Total mKESS scores of the OSA patients were significantly higher than that of the general population. CONCLUSION: The mKESS is more universally applicable for the clinical evaluation of people that live in Korea. Results support that the mKESS can be administered to measure the average daytime sleep propensity of the Korean population as an alternative to the KESS.

Impact of Exposure to Dim Light at Night on Sleep in Female and Comparison with Male Subjects

OBJECTIVE: Light pollution has become a social and health issue. We performed an experimental study to investigate impact of dim light at night (dLAN) on sleep in female subjects, with measurement of salivary melatonin. METHODS: The 25 female subjects (Group A: 12; Group B: 13 subjects) underwent a nocturnal polysomnography (NPSG) session with no light (Night 1) followed by an NPSG session randomly assigned to two conditions (Group A: 5; Group B: 10 lux) during a whole night of sleep (Night 2). Salivary melatonin was measured before and after sleep on each night. For further investigation, the female and male subjects of our previous study were collected (48 subjects), and differences according to gender were compared. RESULTS: dLAN during sleep was significantly associated with decreased total sleep time (TST; F=4.818, p=0.039), sleep efficiency (SE; F=5.072, p=0.034), and Stage R latency (F=4.664, p=0.041) for female subjects, and decreased TST (F=14.971, p<0.001) and SE (F=7.687, p=0.008), and increased wake time after sleep onset (F=6.322, p=0.015) and Stage R (F=5.031, p=0.03), with a night-group interaction (F=4.579, p=0.038) for total sample. However, no significant melatonin changes. There was no significant gender difference of the impact of dLAN on sleep, showing the negative changes in the amount and quality of sleep and the increase in rapid eye movement (REM) sleep in the both gender group under 10 lux condition. CONCLUSION: We found a negative impact of exposure to dLAN on sleep in female as well as in merged subjects. REM sleep showed a pronounced increase under 10 lux than under 5 lux in merged subjects, suggesting the possibility of subtle influences of dLAN on REM sleep.

Association of G-Protein β3 Subunit C825T Polymorphism with Seasonal Variations in Mood and Behavior

OBJECTIVE: Seasonal affective disorder and seasonal changes in mood and behavior are associated with several genes that regulate circadian rhythms. In this study, we investigated the relationship between the C825T polymorphism of the G-protein β3 subunit and seasonal variations in mood and behavior in a young healthy Korean population. METHODS: A total of 507 young Korean participants were recruited through a newspaper advertisement, and their seasonality was evaluated by the Korean version of the Seasonal Pattern Assessment Questionnaire to assess the global seasonality score (GSS). We analyzed the CC, CT, and TT genotypes and their association with the GSS score and subscales. RESULTS: T allele carriers of the GNB3 C825T polymorphism were more likely to score higher on body weight and GSS. In the female group, the T allele carriers obtained significantly high total GSS and its subscale scores for mood, body weight, energy level, and appetite; however, differences in genotypes and allele carriers were also observed in the male participants. CONCLUSION: These results suggested that GNB3 C825T polymorphism plays a role in seasonal variations in mood, body weight, energy level, and appetite in a Korean population, particularly in females.

Haplotype Association of the MAP2K5 Gene with Antipsychotics-Induced Symptoms of Restless Legs Syndrome among Patients with Schizophrenia

OBJECTIVE: Restless legs syndrome (RLS) is considered a genetic disease and, following a genome-wide association study conducted in 2007, the mitogen-activated protein kinase 5 (MAP2K5) gene has been regarded as the promising candidate gene for RLS. The present study investigated whether polymorphisms of MAP2K5 are associated with antipsychotics-induced RLS in schizophrenia. METHODS: We assessed antipsychotics-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Five single-nucleotide polymorphisms (SNPs) of MAP2K5 were genotyped. We investigated genetic and haplotypic associations of these five SNPs with the risk of antipsychotics-induced RLS symptoms. RESULTS: We divided the 190 subjects into 2 groups: 1) those with RLS symptoms (n=96) and 2) those without RLS symptoms (n=94). There were no significant intergroup differences in the distributions of the genotypes and alleles of the rs1026732, rs11635424, rs12593813, rs4489954, and rs3784709 SNPs. However, the haplotype analysis showed that the G-G-G-G-T (rs1026732-rs11635424-rs12593813-rs4489954-rs3784709) haplotype was associated with RLS symptoms (permutation p=0.033). CONCLUSION: These data suggest that a haplotype of MAP2K5 polymorphisms confers increased susceptibility to antipsychotics-induced RLS symptoms in schizophrenic patients.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

Comparison of Wearable Activity Tracker with Actigraphy for Sleep Evaluation and Circadian Rest-Activity Rhythm Measurement in Healthy Young Adults

OBJECTIVE: The purpose of this study was to evaluate the applicability of data obtained from a wearable activity tracker (Fitbit Charge HR) to medical research. This was performed by comparing the wearable activity tracker (Fitbit Charge HR) with actigraphy (Actiwatch 2) for sleep evaluation and circadian rest-activity rhythm measurement. METHODS: Sixteen healthy young adults (female participants, 62.5%; mean age, 22.8 years) wore the Fitbit Charge HR and the Actiwatch 2 on the same wrist; a sleep log was recorded over a 14-day period. We compared the sleep variables and circadian rest-activity rhythm measures with Wilcoxon signed-rank tests and Spearman's correlations. RESULTS: The periods and acrophases of the circadian rest-activity rhythms and the sleep start times did not differ and correlated significantly between the Fitbit Charge HR and the Actiwatch 2. The Fitbit Charge HR tended to overestimate the sleep durations compared with the Actiwatch 2. However, the sleep durations showed high correlation between the two devices for all days. CONCLUSION: We found that the Fitbit Charge HR showed high accuracy in sleep evaluation and circadian rest-activity rhythm measurement when compared with actigraphy for healthy young adults. The results suggest that the Fitbit Charge HR could be applicable on medical research as an alternative tool to actigraphy for sleep evaluation and measurement of the circadian rest-activity rhythm.

Individuals with Restless Legs Syndrome Tend to have Severe Depressive Symptoms: Findings from a Community-Based Cohort Study

Restless legs syndrome (RLS) is a sensorimotor neurological disturbance causing physical and psychological distress. Here, we investigated the severity and effect of depressive symptoms in RLS among a Korean cohort population. Depressive symptoms were more prevalent in the RLS group than in the non-RLS group [≥mild depression: odds ratio (OR)=1.95, p < 0.001; ≥ moderate depression: OR=6.15, p < 0.001; and ≥severe depression: OR=56.54, p < 0.001], with a predominant proportion of severe depression (97%) in the RLS group. We found that difficulty falling asleep (OR=8.16, p < 0.001), broken sleep (OR=11.66, p=0.001), early morning awakening (OR=8.5, p < 0.001), and excessive daytime sleepiness (OR=3.04, p=0.031) were significantly frequent in individuals with severe depression in the RLS group. Red blood cell count was significantly low in individuals with severe depression in the RLS group (p=0.041). We found that severe depression was associated with RLS, suggesting the evaluation and management of mood symptoms and sleep-related and hematological features when treating RLS.

Sleep Irregularity in the Previous Week Influences the First-Night Effect in Polysomnographic Studies

OBJECTIVE: The first-night effect is a well-known phenomenon resulting from an individual's maladaptation to the unfamiliar environment of a sleep laboratory. However, there have been no direct reports of the effect of previous sleep patterns on the first-night effect. We aimed to investigate the effect the previous week's sleep pattern on the first-night effect. METHODS: Twenty-four young, healthy, male participants completed the study procedure. During one week prior to study, the participants kept sleep diaries and wore actigraphs to identify sleep-wake pattern. Two consecutive nights of polysomnography were conducted after that. Wilcoxon signed-rank tests were applied to compare sleep variables of the two nights. Variance (standard deviation) of sleep onset time during the previous week was used as an index of irregularity. A Kendall's ranked correlation analysis and a linear regression test were applied to detect correlation between sleep irregularity and the first-night effect measured by polysomnography. RESULTS: There were significant differences in the values of sleep efficiency (p=0.011) and wake after sleep onset (WASO) (p=0.006) between the two nights. Sleep efficiency was lower and WASO was higher on the first night as compared to the second night. Sleep irregularity in the previous week was negatively correlated with sleep efficiency (p<0.001) of the first night, but was not significantly correlated with any other sleep parameters. CONCLUSION: We replicated the existence of the first-night effect commonly observed in sleep studies. Sleep irregularity in the previous week may influence the first-night effect in polysomnographic studies.

Impact of Dim Artificial Light at Night (dALAN) Exposure during Sleep on Human Fatigue / 수면정신생리

OBJECTIVES: Exposure to light at night has become pervasive in modern society. The impact of dim artificial light at night (dALAN) exposure on sleep and fatigue is not well recognized. We aim to study the impact of dALAN exposure during sleep on human fatigue. METHODS: 30 healthy young male volunteers from 21 to 29 years old were enrolled in the study. They were randomly divided into two groups depending on light intensity (Group A : 5 lux and Group B : 10 lux). Data were gathered from each participant after each night with no light (Night 1) followed by the next night (Night 2) with two different dim light conditions (5 or 10 lux) by means of self-reported fatigue scale. RESULTS: Exposure to dALAN during sleep was significantly associated with increased overall fatigue (F = 19.556, p < 0.001) and ocular discomfort (F = 5.671, p = 0.028). CONCLUSION: We found that dALAN during sleep likely affects human fatigue in some aspects. These findings indicate that dALAN during sleep exerts a negative effect on human fatigue.

Association of the RORA Gene Polymorphism and Diurnal Preference in a Young Korean Population / 수면정신생리

OBJECTIVES: The retinoid-related orphan receptor A (RORA) gene has been reported to have an impact on circadian rhythm regulation. In this study, we analyzed the relationship between the RORA gene polymorphism and diurnal preference in Korean young adults. METHODS: A population of 504 young adults was included in the study. All subjects were given and completed a 13-item composite scale for morningness (CSM). The RORA gene rs11071547 single-nucleotide polymorphism (SNP) was genotyped by PCR-based methods. RESULTS: CSM score was not associated with genotype or allele carrier status of the RORA rs11071547 SNP. CONCLUSION: This result indicates that the RORA rs11071547 SNP does not play a role in diurnal preference.

Recent changes in the concept of treatment of insomnia

A consistent diagnosis and classification system is important to ensure a good understanding of the pathophysiology and ultimate treatment of a disorder. Insomnia is one of the more common complaints encountered in the outpatient setting. Despite the prevalence of insomnia, evaluation, treatment, and research has been hampered by a lack of a standard definition of insomnia. In recent years, there have been important advances in the definition and classification of insomnia. The ICSD-3 and DSM-5 sleep-wake disorder classifications have moved away from the causal attributions that were inherent in previous classifications. The aim is simply to acknowledge the bidirectional and interactive effects between sleep disorders and coexisting medical and psychiatric illnesses. When medical and psychiatric illnesses coexist with insomnia, diagnosis of both disorders allows the plan for the management of insomnia to address both issues and apply comprehensive treatment.

A Comparison of Personality Characteristics and Psychiatric Symptomatology between Upper Airway Resistance Syndrome and Obstructive Sleep Apnea Syndrome

OBJECTIVE: To investigate the personality characteristics of patients with upper airway resistance syndrome (UARS) and those of patients with obstructive sleep apnea syndrome (OSAS). METHODS: Eighty-eight patients with UARS and 365 patients with OSAS participated. All patients had a diagnostic full-night attended polysomnography (PSG) and completed the Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Symptom Checklist-90-Revision (SCL-90-R) and Eysenck Personality Questionnaire (EPQ). RESULTS: The UARS group scored significantly higher than the OSAS group on the ESS, AIS, and PSQI (p<0.001). The scores of all SCL-90-R subscales in the UARS group were significantly higher than those in the OSA group (all p<0.001, except for somatization, p=0.016). Patients with UARS scored lower on EPQ-E (extroversion/introversion) (p=0.006) and EPQ-L (lie) (p<0.001) than those with OSA. UARS patients also showed higher scores on EPQ-P (psychoticism) (p=0.002) and EPQ-N (neuroticism) (p<0.001) than OSAS patients. CONCLUSION: Our results suggest that patients with UARS have worse subjective sleep quality than OSAS patients in spite of their better PSG findings. UARS patients tend to have more neurotic and sensitive personalities than patients with OSAS, which may be a cause of the clinical features of UARS.

MEIS1, a Promising Candidate Gene, Is Not Associated with the Core Symptoms of Antipsychotic-Induced Restless Legs Syndrome in Korean Schizophrenia Patients

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sleep disorder to which individuals appear to be genetically predisposed. In the present study, we assumed that antipsychotic-induced RLS symptoms were attributable to differences in individual genetic susceptibility, and investigated whether MEIS1, a promising candidate gene, was associated with antipsychotic-induced RLS symptoms in schizophrenia patients. METHODS: All subjects were diagnosed with schizophrenia by board-certified psychiatrists using the Korean version of the Structured Clinical Interview for DSM-IV. We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Genotyping was performed for the rs2300478 and rs6710341 polymorphisms of the MEIS1 gene. RESULTS: We divided subjects into RLS symptom (n=96) and non-symptom (n=94) groups. There was no significant between-group difference in the genotype or allele frequencies of the two polymorphisms investigated, nor in the frequency of the rs2300478-rs6710341 haplotype. CONCLUSION: Our data do not suggest that the rs2300478 and rs6710341 polymorphisms of the MEIS1 gene are associated with the core symptoms of antipsychotic-induced RLS in schizophrenia; different genetic mechanisms may underlie antipsychotic-induced vs. primary RLS.

Association between Antipsychotic-Induced Restless Legs Syndrome and Glutathione S-Transferase Gst-M1, Gst-T1 and Gst-P1 Gene Polymorphisms / 수면정신생리

OBJECTIVES: The pathophysiology of restless legs syndrome (RLS) has not been fully elucidated. Oxidative stress might play a role in the development of RLS and other antipsychotic-induced side effects such as tardive dyskinesia. In the present study, we investigated whether the glutathione S-transferase (GST) gene polymorphisms are associated with antipsychotic-induced RLS in schizophrenia. METHODS: We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. The GST-M1, GST-T1 and GST-P1 loci were analyzed using PCR-based methods. RESULTS: We divided the subjects into 2 groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). There were no significant differences in the distributions of the GST-M1 genotypes (chi2 = 3.56, p = 0.059), GST-T1 (chi2 = 0.51, p = 0.476) and GST-P1 (chi2 = 0.57, p = 0.821) between the 2 groups. Comparison of the RLS score among genotypes of the GST-M1 (t = -1.54, p = 0.125), GST-T1 (t = -0.02, p = 0.985) and GST-P1 (F = 0.58, p = 0.560) revealed no significant difference. CONCLUSION: These data suggest that GST gene polymorphisms do not confer increased susceptibility to RLS symptoms in schizophrenic patients. Future studies are necessary to evaluate the possible influences of other candidate genes involved in the reactive oxygen species system.

Acute-Withdrawal Restless Legs Syndrome Following Abrupt Cessation of Short-Term Tramadol

We report a young man who had received tramadol for pain control and experienced an uncomfortable sensation in both legs immediately after tramadol withdrawal that worsened at rest and at night, and which could be relieved only by moving the legs. He suffered from insomnia and paced up and down in his house every night. Readministration of tramadol dramatically resolved his symptoms of restless legs syndrome (RLS), but they reappeared after tramadol withdrawal. Tramadol was therefore replaced with ropinirole, which was discontinued after several weeks, and there was no recurrence of his RLS symptoms. This patient appeared to have developed tramadol-withdrawal-induced RLS, and this case report emphasizes the importance of monitoring for withdrawal-type symptoms like RLS when tramadol intake is being stopped.

Insomnia in Relation to Suicide and Serotonin in Patients with Major Depressive Disorder / 수면정신생리

OBJECTIVES: The aim of current study is to evaluate the relationship between sleep, suicide and serotonin using some scales and loudness dependence of auditory evoked potentials (LDAEP). METHODS: Total 65 patients who met the criteria for major depressive disorder were enrolled in current study. The patients were divided into two subgroups according to their insomnia and a history of suicide attempts. The auditory event-related potentials were measured to evaluate LDAEP before beginning antidepressants. RESULTS: The scores of total Beck Depression Inventory (BDI) and BDI item 9 (suicide) were higher in insomnia subgroup than non-insomnia subgroup (respectively, p=0.0033 and p=0.03). However, LDAEP did not differ each other. The subgroup with a history of suicide attempts had a higher score of BDI item 9 than the subgroup without a history of suicide attempts (p=0.00012). There was a tendency for the LDAEP to be higher in the subgroup with a history of suicide attempts (1.39+/-0.94 microV) than the subgroup without a history of suicide attempts (1.05+/-0.75 microV), although the difference was not statistically significant (p=0.078). CONCLUSION: Suicidality was related to insomnia. In addition, there was a tendency for serotonin activity to be lower in the subgroup with a history of suicide attempts. In future, more studies are needed.

Type-D Personality Can Predict Suicidality in Patients with Major Depressive Disorder

OBJECTIVE: This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD). METHODS: Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied. RESULTS: The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively). CONCLUSION: Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history.

Type-D Personality Can Predict Suicidality in Patients with Major Depressive Disorder

OBJECTIVE: This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD). METHODS: Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied. RESULTS: The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively). CONCLUSION: Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history.

Human Circadian Rhythms / 수면정신생리

A 'circadian rhythm' is a self-sustained biological rhythm (cycle) that repeats itself approximately every 24 hours. Circadian rhythms are generated by an internal clock, or pacemaker, and persist even in the absence of environmental time cues, collectively termed 'zeitgebers.' Although organisms generate circadian rhythms internally, they are entrained by environmental stimuli, particularly the light-dark cycle. Measurement of the endogenous melatonin rhythm provides relatively reliable surrogate way of assessing the timing of the internal circadian clock. Also, core body temperature and cortisol can be used as markers of circadian rhythms. The sleep-wake cycle, body temperature, and melatonin rhythm have a stable internal phase relationship in humans and other diurnal species. They play an important role in controlling daily behavioral rhythms including task performance, blood pressure, and synthesis and secretion of several hormones. In this review, we address not only the properties, methods of measurement, and markers of circadian rhythms, but also the physiological and psychological importance of human circadian rhythms.

Association between Tardive Dyskinesia and Polymorphisms of TNF-alpha Gene in Korean Schizophrenia Patients / 대한정신분열병학회지

OBJECTIVES: There are emerging evidences suggest that the development of tardive dyskinesia (TD) is related to the oxidative stress, excitotoxicity, and immune activation. The purpose of this study is to investigate whether single-nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF)-alpha genes are associated with the susceptibility of TD and schizophrenia. METHODS: We investigated two hundred and eighty Korean schizophrenic patients. The schizophrenic participants consisted of patients with (n=105) and without (n=175) TD who were matched for antipsychotic drug exposure and other relevant variables. The TNF-alpha gene -308G/A SNPs were analyzed by polymerase chain reaction (PCR)-based methods. RESULTS: The frequencies of genotype (chi2=0.33, p=0.848) of the TNF-alpha gene -308 G/A SNP did not differ significantly between schizophrenic patients with and without TD. The difference of allele frequencies (chi2=0.28, p=0.594) of the TNF-alpha gene between the schizophrenic patients with and without TD were not significant. CONCLUSION: These results suggest that the TNF-alpha gene -308 G/A SNPs are not associated with TD and schizophrenia in a Korean population. Further association studies of TD with other candidate genes for cytokines would help us understand the pathophysiological mechanisms of TD.